Herbal medicines as diuretics: A review of the scientific evidence

Journal of Ethnopharmacology 114 (2007) 1–31

Review

Herbal medicines as diuretics: A review of the scientific evidence C.I. Wright ∗ , L. Van-Buren, C.I. Kroner, M.M.G. Koning Nutrition, Nutrition and Health Enhancement, Unilever Food and Health Research Institute, Olivier van Noortlaan 120, P.O. Box 114, 3130 AC, Vlaardingen, The Netherlands Received 20 July 2007; accepted 25 July 2007 Available online 31 July 2007

Abstract There is increasing interest in the health and wellness benefits of herbs and botanicals. This is with good reason as they might offer a natural safeguard against the development of certain conditions and be a putative treatment for some diseases. One such area may be the lowering of blood pressure in those where it is elevated (i.e., hypertension). One class of clinical medicines used to lower blood pressure are known as diuretics and work by increasing the excretion of urine from the body as well as the amount of sodium in urine. There are a growing number of studies purporting diuretic effects with traditional medicines. The aim of this article was to review these studies and identify which extracts promote diuresis (which we assessed on terms of urine excreted and urinary sodium excretion) and also to identify the research needs in this area. We identified a number of species and genuses reporting diuretic effects. Of these, the most promising, at the present time, are the species Foeniculum vulgare, Fraxinus excelsior, Hibiscus sabdariffa, Petroselinum sativum and Spergularia purpurea, and species from the genuses Cucumis (Cucumis melo and Cucumis trigonus), Equisetum (Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum), Lepidium (Lepidium latifolium and Lepidium sativum), Phyllanthus (Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus) and Sambucus (Sambucus mexicana and Sambucus nigra). However, there the number of studies is limited and we recommend that further studies be conducted to confirm reported effects. Such evidence is needed to provide scientific credence to the folklore use of traditional medicines and even be helpful in the development of future medicines, treatments and treatment guidelines. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Medicine; Traditional; Natural; Diuretic; Natriuretic

Contents 1. 2.

3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methodology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. MEDLINE search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Capturing study design and effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Dealing with differences in the duration of the intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Assessing the efficacy of a natural extract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5. Assessing the scientific support for an extract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Alliaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1. Allium sativum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗

Corresponding author at: Unilever R&D Vlaardingen, Olivier van Noortlaan 120, P.O. Box 114, 3130 AC Vlaardingen, The Netherlands. Tel.: +44 7967 230 155; fax: +44 1482 582526. E-mail address: [email protected] (C.I. Wright). 0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2007.07.023

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C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

3.2.

4.

Amaranthaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1. Aerva lanata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Apiaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.1. Foeniculum vulgare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2. Petroselinum sativum (also known as Carum petroselinum and Petroselinum hortense) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4. Asteraceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.1. Taraxacum officinale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5. Brassicaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5.1. Lepidium latifolium and Lepidium sativum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6. Caprifoliaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6.1. Sambucus mexicana and Sambucus nigra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7. Cecropiaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7.1. Cecropia leucocoma and Cecropia pachystachya . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8. Caryophyllaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8.1. Spergularia purpurea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9. Cucurbitaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9.1. Cucumis melo and Cucumis trigonus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10. Equisetaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10.1. Elephantopus scaber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11. Equisetaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11.1. Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12. Euphorbiaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12.1. Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.13. Lamiaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.13.1. Orthosiphon stamineus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.14. Oleaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.14.1. Fraxinus excelsior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.15. Malvaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.15.1. Hibiscus sabdariffa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.16. Oleaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.16.1. Olea europaea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.17. Poaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.17.1. Imperata cylindrica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.17.2. Zea mays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.18. Urticaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.18.1. Urtica dioica . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.19. Zygophyllaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.19.1. Tribulus terrestris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Future needs for this area of research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Hypertension is considered to be a predisposing factor for stroke, coronary heart disease, peripheral arterial disease, heart failure and end-state renal disease (Williams et al., 2004; Godfraind, 2006). Common clinical strategies to achieve a lowering of blood pressure include the use of angiotensin converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers (or CCB’s) and diuretics (Williams et al., 2004; Gallagher et al., 2006). For simplistic reasons, these agents work by reducing arterial resistance and/or decreasing cardiac output. Indeed, ACE inhibitors work by interrupting the conversion of angiotensin-I to angiotensin-II and therefore attenuating the arte-

13 13 13 13 14 15 15 15 15 16 16 17 17 17 17 18 18 18 18 19 19 19 19 20 20 20 20 21 21 22 22 22 22 22 23 23 24 24 24 24 24 28 28

rial constrictor effects of angiotensin-II (Wright et al., 2005). Beta receptor blockers act to counter the stimulatory effects of vascular and cardiac noradrenergic receptors (Rabbia et al., 2001). CCB’s inhibit calcium entry thus decreasing the tone of vascular smooth muscle and promoting vasodilatation (Godfraind, 2006). Diuretics work by promoting the expulsion of urine (measured as the urine volume [UV] excreted) and urinary sodium (UNa) from the body and this helps reduce the volume of blood circulating through the cardiovascular system (Reyes and Taylor, 1999; Williams et al., 2004; Gallagher et al., 2006). In their strictest sense, diuretics are substances that act within the kidney and promote the loss of fluid from the body (Brater,

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

2000). To be clinically effective, however, such compounds must induce the loss of sodium (Lahlou et al., 2006). This is achieved by compounds interfering with the reabsorption of ions, as well as water, through the walls of the kidney tubules (Materson, 1983; Puschett, 1994; Brater, 2000) and this promotes their excretion from the body. There is growing interest in the health benefits of herbs and botanicals (Foote and Cohen, 1998). In line with this there are an increasing number of published articles claiming that plants or plant-derived actives may function as mild diuretic agents. A large majority of this research has determined the degree of clinical support for the traditional use of common or folklore medicines. Such evidence is needed in order to determine whether there is any scientific basis for their use. Of the published studies, we were unclear which plant extracts worked like a clinical diuretic. Therefore, to test this we reviewed all available literature with the intention of (1) capturing what studies had been performed; (2) identifying which extracts had been tested; (3) determining the effect of extracts on UV and UNa. Using this information we hoped to determine the degree of support for each specific extract. Finally, we used this information to identify the future research needs of studies in this area and the potential use of the information from this review. 2. Methodology 2.1. MEDLINE search To determine the evidence to support this idea we conducted a systematic review using the MEDLINE database. All relevant English-language articles published between 1970 and 2005 were searched using the terms ‘natriuresis’, ‘natriuretic’, ‘diuresis’, ‘diuretic’, ‘aquaretic’, ‘urinary flow’, combined with terms ‘food’, ‘herb’, ‘botanical’, ‘nutrient’ or ‘extract’. The search did not include minerals or vitamins. All plant identified were confirmed using http://www.ipni.org. Some extracts [e.g., caffeine containing beverages, Passmore et al., 1987; Bergman et al., 1990; Neuhauser et al., 1997; Armstrong et al., 2005; flavonoids isolated from citrus fruit, Galati et al., 1996; Linoleic acid, Adam and Wolfram, 1984; and glycosides from the leaves of Stevia Rebaudiana, Melis and Sainati, 1991a,b; Melis, 1992a,b,c, 1995, 1996, 1999] and extract decoctions [e.g., the Japanese traditional medicine known as Sairei-to (TJ-114), Fujitsuka et al., 2004, and the polyherbal preparation Jawarish Zarooni Sada, Afzal et al., 2004] were not included as they have no traditional uses in the treatment of urinary or cardiovascular ailments. Table 1 shows the plants identified using our search and indicates whether or not the plant has a traditional ethnopharmacological use. 2.2. Capturing study design and effects Details regarding the study design (dose, model [and strain], population, duration and placebo group) and effects on UV and UNa were captured in a database.

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2.3. Dealing with differences in the duration of the intervention Duration ranged from minutes, to hours, to days and to weeks. In those studies investigating effects occurring within minutes or hours, significant changes refer to a change taking place within the time-frame of the recording period. In longer-term intervention trials, the effect refers to that change reported at the end of intervention phase and not at recording points that may have been performed within this phase. 2.4. Assessing the efficacy of a natural extract We determined whether the volume of urine and/or concentration of sodium in urine changed significantly, with significant increases and decreases shown by ‘+ve’ or ‘−ve’, respectively, and indifferent responses being indicated with a ‘0’. 2.5. Assessing the scientific support for an extract Evidence for the support of an extract was assessed from multiple studies (i.e., >1 article). The spelling of all extracts and family names were checked at http://www.ipni.org. Botanical descriptions were checked using MEDLINE and by referring to http://www.wikipedia.org and http://www.nybg.org. 3. Results Seventy-seven articles were reviewed (see Table 1). Nine of these were human intervention trials (see Table 2); 13 were conducted in anaesthetised animals (Table 3); and 55 were performed in conscious animals (Table 4). These were reviewed to identify multiple references to a particular species or genus. These findings are discussed below, where species have been grouped by family. 3.1. Alliaceae 3.1.1. Allium sativum 3.1.1.1. Botanical description. Allium sativum is a perennial herb and grows top a length of roughly two feet (Grover et al., 2002). The bulb is the part used in traditional medicine and consists of between 4 and 20 cloves. Originally it comes from central Asia, but is now cultivated throughout the world. 3.1.1.2. Ethnobotany. Allium sativum is commonly used as a flavouring agent and has been used as a traditional medicine for thousands of years (Rahman and Lowe, 2006). Its main active is allicin, which is responsible for its characteristic smell and has been used for its anti-bacterial properties (Wright et al., 2005). Allium sativum is reputed to offer protection against strokes, coronary thrombosis, atherosclerosis and platelet aggregation, and work as an anti-hypertensive, anti-hyperglycaemic and anti-hyperlipidemic agent (Sharafatullah et al., 1986; Ribeiro et al., 1988; Pantoja et al., 1991, 1996, 2000; Grover et al., 2002). In traditional medicine, it is administered as a diuretic

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Table 1 An overview of plants with putative diuretic effects Species

Common names

Traditional diuretic use?

Part used

Reference

Alismataceae

Amazon sword plant specie

N (anti-hypertensive)

Leaf

Ribeiro et al. (1988)

Alliaceae

Echinodorus grandiflorus (Cham. & Schltdl.) Micheli Allium sativum L.

Garlic

N (anti-hypertensive)

Bulb

Amaranthaceae

Aerva lanata Linn.

Y (urinary infections)

Plant; leaf; flower

Annonaceae

Xylopia aethiopica A.Rich.

N

Fruit

Apiaceae

N

Rhizome

Somova et al. (2001)

Y N (anti-hypertensive)

Ripe fruit Seed

Lahlou et al. (2006) Ribeiro et al. (1988)

Apiaceae

Alepidea amatymbica Eckl. & Zeyh. Carum carvi L. (see Petroselium) Carum petroselinum Benth. & Hook.f. Coriandrum sativum L.

Common Sri Lankan Herb, Kapurijadi, Katumpangan Ayer, Oepas Oepan, Pindi kura, Pindi Kura, Roempoet Oepas Oepan, Wool Plant, Ethiopian pepper plant, Guinea pepper plant Larger tinsel flower, Kalmoes, Iqwili, Ikhathazo Caraway Parsley

Pantoja et al. (1991, 1996, 2000), Ribeiro et al. (1988), Sharafatullah et al. (1986) Goonaratna et al. (1993), Selvam et al. (2001), Udupihille and Jiffry (1986) Somova et al. (2001)

Coriander

N

Seed

Apiaceae

Foeniculum vulgare L.

Fennel

Y

Root

Apiaceae Apiaceae

Fennel Fennel

Y Y

Root; rhizome Fruit

Apiaceae

Foeniculum vulgare Mill Foeniculum vulgare var dulce (D.C.) Petroselinum hortense Hoffm.

Udupihille and Jiffry (1986) Beaux et al. (1997), Caceres et al. (1987), El Bardai et al. (2001) Caceres et al. (1987) El Bardai et al. (2001)

Parsley

Y

Seeds

Apiaceae

Petroselinum sativum Hoffm.

Parsley

Y

Seedlings

Apiaceae Apocynaceae

Steganotaenia araliacea Hochst. Apocynum venetum L.

Y Y

Bark Leaf

Apocynaceae Asteraceae Asteraceae

Carissa edulis Vahl Achyrocline satureioides DC. Artemisia thuscula Cav.

Y N Y

Root Inflorecences Aerial part

Asteraceae Asteraceae Asteraceae Asteraceae

Bidens odorata Cav. Centaurea phyllocephala Boiss. Cichorium endivia L. Helichrysum ceres

Carrot tree LuoBuma in Chinese; Rafuma in Japanese Natal Plum Macela Artemisia thuscula, an endemic species of the Canary Islands Common black jack A common weed Endive Unclear

Y (renal disorders) N (anti-hypertensive) N (anti-hypertensive) N (anti-hypertensive)

Aerial part Leaf Leaf Leaf; root

Asteraceae Asteraceae

Hieracium pilosella L. Mikania glomerata Spreng.

Y N (anti-hypertensive)

Aerial part Leaf

Apiaceae Apiaceae

Mouseear hawkweed Guaco, guace, bejuco de finca, cepu, liane Francois, matafinca, vedolin, cip´o caatinga, huaco, erva das serpentes, corac¸a˜ o de Jesus, erva-de-cobra, guaco-de-cheiro

Kreydiyyeh and Usta (2002) Kreydiyyeh and Usta (2002) Agunu et al. (2005) Kim et al. (2000) Nedi et al. (2004) Rocha et al. (1994) Benjumea et al. (2005) Camargo et al. (2004) Twaij et al. (1983) Ribeiro et al. (1988) Musabayane et al. (2003) Beaux et al. (1999) Ribeiro et al. (1988)

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Family

Solidago gigantea Ait. Spilanthes acmella Murr.

Giant goldenrot (Herb) Toothache Plant, Paracress

N Y

Plant Flowers

Asteraceae Asteraceae

Tanacetum vulgare L. Taraxacum officinale Weber

Common tansy Dandelion

Y Y

Asteraceae Bignoniaceae Brassicaceae Brassicaceae

Vernonia polyanthes Less. Tecoma stans (L.) H.B. & K. Eruca sativa Mill. Lepidium latifolium L.

Weed: Assa peixe, chamarrita Trumpetbush, yellow elder, yellowbells Rocket, garden rocket, rocketsalad Pepperweed (broad leaved)

N (anti-hypertensive) Y (urinary ailments) N (anti-hypertensive) Y (renal disorders)

Leaf Root (Hook et al., 1993; Racz-Kotilla et al., 1974), herb (Racz-Kotilla et al., 1974) Leaf Bark Leaf Seed

Brassicaceae Brassicaceae Brassicaceae Bromeliaceae

Lepidium sativum L. Nasturtium officinale R.Br. Raphanus sativus L. Ananas comosus (L.) Merr.

Pepperweed (garden cress) Watercress Radish Pineapple, Nana of the Tupi Indians

Y (renal disorders) N (anti-hypertensive) Y (urinary disease) Y (renal disorders)

Leaf Aerial parts Bark Root

Cactaceae

Opuntia ficus-indica (L.) Mill.

Y

Caprifoliaceae

Sambucus mexicana Presl ex DC.

Prickly pear, cactus pear, Indian fig, Barbary fig Elderberry (Mexican)

N

Cladode; fruit; flower Flower

Caprifoliaceae

Sambucus nigra L.

Elderberry (European)

Y (urinary ailments)

Bark

Caricaceae

Carica papaya L.

Papaya, Pawpaw, Melon tree

Y (dysuria)

Root

Caryophyllaceae Cecropiaceae Cecropiaceae

Spergularia purpurea Cecropia leucocoma Miq. Cecropia pachystachya Tr´ecul

Sand spurrey Cantalope tree Ambay; Trumpet tree

Y (kidney disease) Y Y

Plant Leaf Leaf

Costaceae Cucurbitaceae

Costus spiralis Rosc. Cucumis melo

Y Y

Plant Seed

Cucurbitaceae Cucurbitaceae Cyperaceae

Cucumis trigonus Roxb. Sechium edule Sw. Cyperus rotundus L.

Spiral ginger Cantaloupe, Melon, Muskmelon, Honeydew, Sugar melon Kolhi Kekdi (melon family) Chayote Cocograss, nutgrass

N N (anti-hypertensive) Y (dysuria)

Fruit Leaf; seed Rhizome

Equisetaceae

Elephantopus scaber

Y

Plant

Equisetaceae

Equisetum (fluviatile; hiemale var. affine; giganteum; myriochaetum) Equisetum bogotense Kunth

Elephant’s Foot, Bull’s Tongue, Ironweed, Dog’s tongue Horsetail (Swamp/Giant/Scouring rush/Mexican)

Y

Plant

Andean Horsetail

Y

Stem

Equisetaceae

Leuschner (1995) Ratnasooriya et al. (2004) Lahlou et al. (2006) Hook et al. (1993), Racz-Kotilla et al. (1974)

Ribeiro et al. (1988) Caceres et al. (1987) Ribeiro et al. (1988) Maghrani et al. (2005b), Navarro et al. (1994) Navarro et al. (1994) Ribeiro et al. (1988) Vargas et al. (1999) Sripanidkulchai et al. (2001) Galati et al. (2002) Beaux et al. (1999), Caceres et al. (1987) Beaux et al. (1999), Caceres et al. (1987) Sripanidkulchai et al. (2001) Jouad et al. (2001b,c) Ribeiro et al. (1988) Consolini and Migliori (2005) Araujo et al. (1999) Singh and Sisodia (1970) Naik et al. (1981) Ribeiro et al. (1988) Sripanidkulchai et al. (2001) Laranja et al. (1991), Poli et al. (1992) Perez Gutierrez et al. (1985)

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

Asteraceae Asteraceae

Lemus et al. (1996)

5

6

Table 1 (Continued ) Species

Common names

Traditional diuretic use?

Part used

Reference

Ericaceae

Arctostaphylos uva-ursi (L.) Spreng. Acalypha guatemalensis Pax & K.Hoffm. Euphorbia hirta

Bearberry

Y

Leaf

Beaux et al. (1999)

Cattail like plant; local plant in Guatemala Cats hair, asthma weed, basri dudhi, chara, malnommee, pill - bearing spurge, patikan kerbau, patikan kebo, fei yang cao, gelang susu, amampat chaiarisi, erva de santa luzia black catnip,child pick-a-back, bhuiamla, gulf leafflower, meniran, chanca piedra, shatterstone, stone breaker, quebra pedra, bahupatra, gale of wind, carry me seed, hsieh hsia chu. Local Indian herb

Y (urinary ailments)

Leaf

Caceres et al. (1987)

N

Leaf

Johnson et al. (1999)

Y

Plant

Srividya and Periwal (1995)

N (anti-hypertensive)

Aerial parts

Ribeiro et al. (1988)

Sarand´ı blanco

Y

Bark

Hnatyszyn et al. (1999) Haloui et al. (2000) Rhiouani et al. (1999) Lu et al. (1994)

Euphorbiaceae Euphorbiaceae

Euphorbiaceae

Phyllanthus amarus Schumach. & Thonn.

Euphorbiaceae

Phyllanthus corcovadensis M¨ull.Arg. Phyllanthus sellowianus M¨ull.Arg. Centaurium erythraea Rafn Herniaria glabra Clerodendrum trichotomum Thunb. Marrubium vulgare L. Ocimum micranthum Willd. Orthosiphon stamineus Benth./Orthosiphon folium

Common centaury Smooth rupturewort Harlequin Glorybower

Y (urinary retention and abdominal colic) Y N (anti-hypertensive)

Plant Aerial part Leaf

Horehound Alfavaca Cat’s whiskers Java Tea and extract (Methylripariochromene)

N (anti-hypertensive) N (anti-hypertensive) Y

Leaf Leaf; aerial part

Lamiaceae Lamiaceae Lauraceae Leguminosae

Rosmarinus officinalis L. Salvia officinalis L. Persea gratissima Gaertn. Retama raetam Webb & Berthel.

Rosemary Sage Avocado White weeping broom

Y (urinary ailments) N (anti-hypertensive) N (anti-hypertensive) N (anti-hypertensive)

Leaf Leaf Leaf Plant

Leguminosae Liliaceae Loganiaceae Lythraceae

Vicia faba L. Allium cepa L. Strychnos potatorum Linn. Cuphea calophylla Cham. & Schltdl.

Broad bean Garden onion Clearing nut Local Plant from Central America

N N (anti-hypertensive) Y N (anti-hypertensive)

Seedlings Bulb Seed Leaf

Euphorbiaceae Gentianaceae Illecebraceae Lamiaceae Lamiaceae Lamiaceae Lamiaceae

El Bardai et al. (2001) Ribeiro et al. (1988) Beaux et al. (1999), Doan et al. (1992), Englert and Harnischfeger (1992), Matsubara et al. (1999), Olah et al. (2003) Haloui et al. (2000) Ribeiro et al. (1988) Ribeiro et al. (1988) Maghrani et al. (2005a) Vered et al. (1997) Ribeiro et al. (1988) Biswas et al. (2001) Ribeiro et al. (1988)

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Family

Hibiscus sabdariffa L.

Roselle

Y (urinary ailments)

Calyx; petals (Odigie et al., 2003)

Menispermaceae Moringaceae

Cocculus hirsutus (L.) Diels Moringa oleifera Lam.

Jack-switch Horseradish tree

Y N (anti-hypertensive)

Musaceae Myristicaceae Myrtaceae Oleaceae

Musa sapientum L. Myristica fragrans Houtt. Eugenia uniflora O.Berg Fraxinus excelsior L.

Banana Nutmeg Surinam cherry Ash tree

N (anti-hypertensive) N (anti-hypertensive) N (anti-hypertensive) Y (facilitate renal excretion)

Aerial part Bark; stalk; leaf; root; seed Leaf Seed Leaf Leaf

Oleaceae

Olive

Y

Leaf

Oxalidaceae

Olea europaea L. (African; Greek; and, cultivar from Cape Town) Averrhoa carambola L.

Starfruit, Carabola, Caramba

Y (renal disorders)

Root

Passifloraceae Piperaceae

Passiflora edulis Sims Piper chaba Hunter

Passion fruit Long pepper

N (anti-hypertensive) N

Leaf Bark

Plantaginaceae Poaceae Poaceae

Plantago major L. Coix lacryma-jobi L. Cymbopogon citratus Stapf

Broad-leaved plantain Job’s tears Lemon grass

N N (anti-hypertensive) N (anti-hypertensive)

Seed Leaf Root

Poaceae

Imperata cylindrica Beauv.

Y

Rhizome

Poaceae

Imperata cylindrica Linn.

Y

Leaf

Poaceae Poaceae Poaceae

Phalaris canariensis L. Saccharum officinarum L. Zea mays L.

Cogon grass, Cotton grass, Lalang, KunaiJapanese blood grass Cogon grass, Cotton grass, Lalang, KunaiJapanese blood grass Canary grass Sugarcane Corn

N (anti-hypertensive) N (anti-hypertensive) Y

Seed Leaf Stigmata

Polygalaceae

Bredemeyera floribunda Willd.

Y

Root

Polypodiaceae

Phlebodium aureum (L.) J.Sm.

Y (urinary ailments)

Root; rhizome

Local Plant from amazone, belongs to the knotweed family Cabbage palm fern, Golden polypody, Golden serpent fern

Caceres et al. (1987), Herrera-Arellano et al. (2004), Onyenekwe et al. (1999), Herrera-Arellano et al. (2004), Onyenekwe et al. (1999) Ganapaty et al. (2002) Caceres et al. (1992) Ribeiro et al. (1988) Ribeiro et al. (1988) Consolini et al. (1999) Casadebaig et al. (1989), Eddouks et al. (2005) Ribeiro et al. (1988), Somova et al. (2003) Sripanidkulchai et al. (2001) Ribeiro et al. (1988) Taufiq-Ur-Rahman et al. (2005) Doan et al. (1992) Ribeiro et al. (1988) Doan et al. (1992), Sripanidkulchai et al. (2001) Sripanidkulchai et al. (2001) Carbajal et al. (1989)

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Malvaceae

Ribeiro et al. (1988) Ribeiro et al. (1988) Al Ali et al. (2003), Doan et al. (1992), Maksimovic et al. (2004), Ribeiro et al. (1988), Velazquez et al. (2005) Bevevino and Aires (1994) Caceres et al. (1987)

7

8

Table 1 (Continued ) Species

Common names

Traditional diuretic use?

Part used

Reference

Portulacaceae Ranunculaceae Rosaceae Rosaceae Rubiaceae Rubiaceae

Chisme, kiss me quick Clematis montevidensis Brazilian/Mauritius raspberry West ndian Raspberry Cafezinho South american Shrub from the coffee family Unclear

Y N N (anti-hypertensive) N (anti-hypertensive) N (anti-hypertensive) N (anti-hypertensive)

Leaf Root; aerial part Leaf Leaf Leaf Leaf

Rocha et al. (1994) Alvarez et al. (2003) Ribeiro et al. (1988) Ribeiro et al. (1988) Ribeiro et al. (1988) Ribeiro et al. (1988)

N (anti-hypertensive)

Leaf

Ribeiro et al. (1988)

Papache

Y (urinary disease)

Fruit

Rutaceae Scrophulariaceae Solanaceae Solanaceae Solanaceae

Portulaca pilosa L. Clematis montevidensis Spreng. Rubus brasiliensis Mart. Rubus rosaefolius Sm. Palicourea marcgravii A.St.-Hil. Psychotria malaneoides M¨ull.Arg. Psychotria sessilis (Vell.) M¨ull.Arg. Randia echinocarpa Sess´e & Moc. ex DC. Citrus limonum Risso Digitalis purpurea Fabiana patagonica Speg. Solanum paniculatum L. Withania somnifera Dunal

Lemon Common foxglove, purple foxglove Local Andian shrub Jurubeba Winter cherry, ashwagandha

N (anti-hypertensive) N Y N (anti-hypertensive) N

Fruit Fruit Aerial part Leaf Root

Ternstroemiaceae

Visnea mocanera L.

Mocan

N

Leaf

Urticaceae

Urtica dioica L.

Stinging nettle

Y (urinary ailments)

Leaf; aerial part

Zingiberaceae Zingiberaceae

Alpinia speciosa Hedychium coronarium J.Koenig

Y N (anti-hypertensive)

Zygophyllaceae

Tribulus terrestris L.

Shell plant White ginger, butterfly ginger, ginger lily, white butterfly ginger lily, garland flower Puncture Vine, Caltrop, Yellow Vine

Plant Leaf blade; sheath; stem Leaf (Al Ali et al., 2003); fruit (Al Ali et al., 2003; Singh and Sisodia, 1971)

Vargas and Perez Gutierrez (2002) Ribeiro et al. (1988) Navarro et al. (2000) Alvarez et al. (2002) Ribeiro et al. (1988) Andallu and Radhika (2000) Hernandez-Perez et al. (1995) Caceres et al. (1987), Tahri et al. (2000) Laranja et al. (1991) Ribeiro et al. (1988)

Rubiaceae Rubiaceae

Note that common names were identified by referring to research articles and visiting http://plants.usda.gov.

Y (kidney disease)

Al Ali et al. (2003), Singh and Sisodia (1971)

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Family

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

9

Table 2 Summary of studies reporting effects on urinary volume (UV) and sodium (UNa) in humans Scientific name

Dose

Reference

Study (design/R?/PL?/n)

Duration

UV

UNa

Aerva lanata (leaf; flower; stem) Aerva lanata (leaf; flower; stem) Coriandrum sativum Alpinia speciosa Elephantopus scaber Equisetum bogotense Hibiscus sabdariffa Imperata cylindrica (IC) Orthosiphon stamineus (OS) Plantago major (PM) Zea mays (ZM) Mix Phyllanthus amarus Vicia faba Withania somnifera

200 ml decoction 200 ml of 50–100 g l−1 200 ml of 50 g l−1 0.8 g 100 ml−1 7.5 g 100 ml−1 0.75 g 10 g 50 g 10 g 20 g 40 g 120 g ZM, 50 g IC, 20 g PM 5g 40 g 3 g d−1

Goonaratna et al. (1993) Udupihille and Jiffry (1986)

CO/Y/Y/n = 14 P/N/N/n = U

10 h 1.5 h

Laranja et al. (1991)

CO/N/Y/n = 10

6h

Lemus et al. (1996) Herrera-Arellano et al. (2004) Doan et al. (1992)

CO/N/N/n = 25 P/Y/N/n = 45 CO/Y/Y/n = 40

2d 4 wk 1d

Srividya and Periwal (1995) Vered et al. (1997) Andallu and Radhika (2000)

P/N/N/n = 7 P/N/N/n = 12 P/N/N/n = 12

10 d 3h 30 d

0 +ve 0 +ve 0 +ve – 0 0 0 0 0 +ve – +ve

0 – – 0 0 +ve +ve 0 0 0 0 0 +ve +ve +ve

Study refers to the design (P, parallel; CO, cross-over), whether the study was randomised (R?), whether a placebo control group (PL?) was included (simply yes [Y] or no [N]) and the population size (n). Duration is shown in hours (h), days (d) and weeks (wk). Dosage is shown when it was reported. Other abbreviations: U, unclear; ‘+ve’ and ‘−ve’ represent significant increases and decreases, respectively; ‘0’, no change; and, ‘–’, indicates when a parameter was not measured.

agent, yet, until 1988, no controlled studies had assessed these effects. 3.1.1.3. Diuretic activity. Five studies (Sharafatullah et al., 1986; Ribeiro et al., 1988; Pantoja et al., 1991, 1996, 2000) have tested the diuretic effect of Allium sativum. Pantoja et al. (1991, 1996, 2000) has performed three trials in anaesthetised animals. The first (Pantoja et al., 1991) used anaesthetised, saline hydrated dogs and urine flow was monitored following cannulation of the ureters. A powdered extract Allium sativum was administered intra-gastrically and increased UV and UNa, with between 30 and 40 min. Blood pressure was also decreased by this extract. Unfortunately, however, no statistical comparisons

were performed and responses were deemed indifferent. The second trial (Pantoja et al., 1996) used anaesthetised rabbits and the same experimental set-up as above). A purified fraction of Allium sativum was intravenously injected and increased UV and UNa in a dose-dependently fashion. It also decreased arterial blood pressure, but, again, no statistics were reported. The third study performed was in anaesthetised dogs (Pantoja et al., 2000) and used a purified fraction of Allium sativum. Following the intravenous injection of a. Allium sativum, UV (∼0.1 to ∼0.6 ml min−1 ) and UNa (0.4–3.2 mEq 10 min−1 ) were significantly increased from baseline levels. The mechanism was suggested to be via inhibition of kidney membrane N+ , K+ ATPase.

Table 3 Summary of studies in anaesthetised animals reporting effects on urinary volume (UV) and sodium (UNa) excretion Scientific name

Dose

Reference

Animal-strain/PL?/n

Duration (h)

UV

UNa

Allium sativum Allium sativum Allium sativum

2.5–15 mg kg−1 2, 4, 6 ␮g kg−1 6 ␮g kg−1

Pantoja et al. (1991) Pantoja et al. (1996) Pantoja et al. (2000)

D-M/N/n = 3 Rab-U/N/n = 6 D-M/N/n = 8

10 1.5 4.3

0 0 0

0 0 0

Allium sativum

25.9, 54 mg kg−1 13.5 mg kg−1

Sharafatullah et al. (1986)

D-M/N/n = 24

0.5

+ve 0

– –

Bredemeyera floribunda Citrus limonum Clerodendron trichotomum Cucumis melo Helichrysum ceres (leaf) Helichrysum ceres (root) Hibiscus sabdariffa

0.05 mg min−1 100 g−1 25 ml kg−1 of 10–20% decoction 0.24 g kg−1 300–400 mg 0.3, 0.6, 1.2 ␮g min−1 0.3, 3, 6 ␮g min−1 250 mg kg−1 d for 8 wks

Bevevino and Aires (1994) Carbajal et al. (1989) Lu et al. (1994) Singh and Sisodia (1970) Musabayane et al. (2003)

R-W/N/n = 9 R-W/Y/n = 32 R-SD/N/n = 10 D-M/N/n = U R-SD/Y/n = 48

1.5 5 1.58 0.5 7

Odigie et al. (2003)

1.5

+ve – +ve – +ve +ve –

Retama raetam Tribulus terrestris (aqueous) Tribulus terrestris (ether) Urtica dioica

200 mg kg−1 for 3 wk 10 g in 100 ml 300–400 mg 4, 24 mg kg−1

Maghrani et al. (2005a) Singh and Sisodia (1971)

R-SD (normal/hypertensive)/Y/n = 15 R-W/Y/n = 9 D-M/N/n = U

+ve 0 0 +ve 0 +ve 0

Tahri et al. (2000)

R-W/N/n = 16

3.75

+ve 0 +ve +ve

– – – +ve

4 0.5

The type of extract is shown in brackets. Animal (R, rat; D, dog; Rab, rabbit) and strain (W, Wistar; SD, Sprague-Dawley; M; mongrel) are indicated. PL?, refers to whether a placebo control group was included (simply yes [Y] or no [N]). Population is shown with an n. Duration is the same as in Table 2. U, unclear; h, hour; d, day; Y, yes; N, no. Other abbreviations: U, unclear; ‘+ve’ and ‘−ve’ represent significant increases and decreases, respectively; ‘0’, no change; and, ‘–’, indicates when a parameter was not measured.

10

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Table 4 Summary of studies reporting effects on urinary volume (UV) and sodium (UNa) excretion in chronic animals Scientific name

Dose

Reference

Animal-strain/ PL?/Admin?/n

Duration

UV

UNa

Aerva lanata (leaf; with ethylene glycol) Bidens odorata Carissa edulis (bark extract, wood maceration) Carissa edulis (wood extract) Carissa edulis (bark maceration) Carum carvi Tanacetum vulgare Centaurium erythraea

6 ml kg−1 day−1

Selvam et al. (2001)

R-A/Y/G/36

28 d

+ve

–

41, 166 mg kg−1 50–100 mg kg−1

Camargo et al. (2004) Nedi et al. (2004)

R-W/Y/O/n = 37 R-U/Y/O/n = 40

6h 5h

+ve +ve

+ve +ve

+ve 0 +ve +ve +ve

0 0 +ve +ve +ve +ve +ve 0 +ve 0 +ve

Centaurium erythraea Rosmarinus officinalis Rosmarinus officinalis Euphorbia hirta (aqueous) Euphorbia hirta (ethanol) Equisetum fluviatile; E. hiemale var. affine, E. giganteum, E. myriochaetum) Spergularia purpurea

100 mg kg−1

Lahlou et al. (2006)

R-W/Y/O/n = 15-20

8d

10 ml kg−1 ; 8% decoction 16% 8% 16% 50, 100 mg kg−1 50, 100 mg kg−1 50 mg kg−1

Haloui et al. (2000)

R-W/Y/O/n = 30

7d

Johnson et al. (1999)

R-W/Y/IP/n = 57

1d

Perez Gutierrez et al. (1985)

M-CD1/Y/O/n = U

6h

0 +ve 0 +ve +ve +ve

100, 200, 400 mg kg−1 5 mg kg−1 500 mg kg−1

Jouad et al. (2001b)

R-W/Y/O/n = 30

28 d

+ve

+ve

Jouad et al. (2001c) Caceres et al. (1987)

R-SHR&W/Y/O/n = 36 R-A/Y/G/n = 54

7d 6h

190 mg kg−1 190 mg kg−1 80 mg kg−1 80 mg kg−1

El Bardai et al. (2001)

R-SHR/Y/O/n = 61 R-WKY R-SHR R-WKY

5d

+ve 0 +ve 0 0 0 0 0 +ve 0 +ve 0

+ve 0 +ve 0 0 0 – – +ve 0 0 0

Fraxinus excelsior

20 mg kg−1

Eddouks et al. (2005)

R-WKY/Y/O/n = 30 R-SHR

21 d

+ve 0

+ve +ve

Herniaria glabra (saponins)

200 mg kg−1

Rhiouani et al. (1999)

R-SHR/Y/O/n = 15

30 d

+ve

+ve

Hibiscus sabdariffa

Unclear (∼500–1000 mg kg−1 )

Onyenekwe et al. (1999)

R-SHR/Y/G/n = 15

24 h

+ve

–

0

–

Spilanthes acmella

500, 1000 mg kg−1

Ratnasooriya et al. (2004)

5h

0

0

+ve

+ve

+ve

+ve

0

+ve

Spergularia purpurea (flavanoids) Foeniculum vulgare Hibiscus sabdariffa Acalypha guatemalensis Sambucus nigra Tecoma stans Phlebodium aureum Urtica dioica Foeniculum vulgare Foeniculum vulgare Marrubium vulgare Marrubium vulgare

R-WKY

1500 mg kg−1 Lepidium latifolium

20 mg kg−1

Maghrani et al. (2005b)

R-A/Y/O/n = 30

R-WKY/Y/O/n = 30

21 d

R-SHR 100 mg kg−1

Lepidium sativum

50, 100 mg kg−1 50 mg kg−1

Navarro et al. (1994)

R-W/Y/G/n = 30 R-W/Y/IP R-W/Y/IP

6h

+ve +ve 0

0 0 0

Artemisia thuscula

0.25, 0.50 g kg−1

Benjumea et al. (2005)

R-SD/Y/O/n = 40

8h

+ve

+ve

0.75 g kg−1

0

+ve

Tribulus terrestris Zea mays Tribulus terrestris and Zea mays

5 g kg−1 5 g kg−1 5 g & 5 g kg−1

Al Ali et al. (2003)

R-W/Y/O/n = 30

1d

+ve 0 +ve

+ve 0 +ve

Zea mays

10 ml kg−1 of 5% decoction 10%

Maksimovic et al. (2004)

R-W/Y/O/n = 24

9d

+ve

+ve

0

+ve

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11

Table 4 (Continued ) Scientific name

Dose

Reference

Animal-strain/ PL?/Admin?/n

Duration

UV

UNa

Phyllanthus sellowianus

400 mg kg−1

R-SD/Y/O/n = 30

8h

+ve

+ve

Strychnos potatorum

200, 400 mg kg−1 600 mg kg−1

Hnatyszyn et al. (1999) Biswas et al. (2001)

R-W/Y/O/n = 30

5h

+ve +ve

+ve 0

Ananas comosus

5, 10 g kg−1

R-SD/Y/O/n = 96

4h

+ve

0

Carica papaya Carica papaya Averrhoa carambola Cyperus rotundus Imperata cylindrica Steganotaenia araliacea (ethanol, methanol, water) Orthosiphon folium

10 g kg−1 5 g kg−1 5, 10 g kg−1 5, 10 g kg−1 5, 10 g kg−1 20 mg kg−1

0 0 0 0 0 0

Clematis montevidensis (active, oleanolic acid) Clematis montevidensis (aerial part, root) Fabiana patagonica (active, oleanolic acid) Fabiana patagonica (plant, acetone) Petroselinum hortense, Petroselinum sativum Allium cepa

125, 750, 1000 mg kg−1 200 mg kg−1

Sripanidkulchai et al. (2001)

Agunu et al. (2005)

R-W/Y/IP/n = 30

1d

+ve 0 0 0 −ve +ve

Englert and Harnischfeger (1992) Alvarez et al. (2003)

R-W/Y/G/n = U

U

0

0

R-W/Y/G/n = U

3h

+ve

0

0

0

10% w/w 200 mg kg−1

Alvarez et al. (2002)

R-W/Y/G/n = U

3h

+ve

–

250 mg kg−1 20 g prepared in 100 ml 40 ml kg−1 of a 50:50 v/v decoction

Kreydiyyeh and Usta (2002) Ribeiro et al. (1988)

R-SD/Y/O/n = 6

1d

+ve +ve

– –

R-W/Y/O/n = 191

4h

+ve

– – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – –

Allium sativum Carum petroselinum Cecropia leucocoma Cichorium endivia Citrus limonum Coix lacryma-jobi Cuphea calophylla Echinodorus grandiflorus Eruca sativa Hedychium coronarium Mikania glomerata Musa sapientum Myristica fragrans Nasturtium officinale Ocimum micranthum Olea europaea Palicourea marcgravii Passiflora edulis Persea gratissima Phalaris canariensis Phyllanthus corcovadensis Psychotria sessilis Psychotria malaneoides Rubus brasiliensis Rubus rosaefolius Saccharum officinarum Salvia officinalis Sechium edule Solanum paniculatum Vernonia polyanthes Zea mays Olea europaea

60 mg kg−1

Somova et al. (2003)

R-Dahl/Y/IP/n = 42

1d

+ve +ve +ve +ve +ve +ve +ve +ve 0 +ve +ve +ve +ve 0 0 0 +ve +ve +ve +ve +ve +ve +ve +ve +ve +ve 0 +ve 0 +ve +ve 0

Randia echinocarpa

10 mg kg−1

Vargas and Perez Gutierrez (2002)

R-A/Y/G/n = U

1d

0

–

+ve

–

0

+ve

20, 40, 60 mg kg−1 Cocculus hirsutus

100,

200 mg kg−1

Ganapaty et al. (2002)

R-W/Y/O/n = 24

5h

12

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

Table 4 (Continued ) Scientific name

Dose

Reference

Animal-strain/ PL?/Admin?/n

Duration

UV

UNa

Apocynum venetum (roasted, unprocessed) Taraxacum officinale

70 mg d−1

Kim et al. (2000)

R-W/Y/O/n = 24

100 d

0

0

50 ml kg−1 of a 0.5–6 g ml−1 decoction 25, 50, 200, 350, 500 mg kg−1 100, 300, 1000 mg kg−1 3000 mg kg−1

Racz-Kotilla et al. (1974)

R&M-U/Y/G&O/n = 16

30 d

0

0

Velazquez et al. (2005) Leuschner (1995)

R-W/N/G/n = U

5h

0

0

R-SD/Y/O/n = U

5–24 h

0

0

+ve

0

50 mg kg−1

Beaux et al. (1999)

R-SD/Y/IP/n = 145

8–24 h

Galati et al. (2002)

R-W/Y/O/n = 150

1 wk

+ve 0 +ve +ve +ve 0

0 0 0 0 +ve 0

25, 50 mg kg−1 100, 300 mg kg−1

Naik et al. (1981) Poli et al. (1992)

R-H/Y/O/n = 9 R-W/N/U/n = 8-10

6h U

+ve +ve 0

0 +ve –

750, 1000 mg kg−1 1000 mg kg−1 750 mg kg−1 40, 70, 140 mg kg−1

Caceres et al. (1992)

R-A/Y/O/n = U

6h

Vargas et al. (1999)

R-A/Y/O/n = U

24 h

0 +ve 0 +ve

– – – –

Zea mays Solidago gigantean

Arctostaphylos uva-ursi Hieracium pilosella Hieracium pilosella Orthosiphon stamineus Sambucus nigra Opuntia ficus-indica (cladode) Opuntia ficus-indica (flower, fruit) Cucumis trigonus Elephantopus scaber (aqueous, alcoholic) Moringa oleifera (leaf, roots, stalk) Moringa oleifera (seeds) Moringa oleifera (seeds) Raphanus sativus

50 mg kg−1 200 mg kg−1 50 mg kg−1 50 mg kg−1 5 ml 100 g of a 15% decoction

100 mg kg−1

Foeniculum vulgare

25, 50, 200 mg kg−1

Beaux et al. (1997)

R-SD/Y/IP/n = 157

24 h

0 +ve

– +ve

Fraxinus excelsior (alcoholic)

140 mg kg−1

R-W/Y/G/n = 25

6h

0

0

Fraxinus excelsior (alcoholic) Fraxinus excelsior (aqueous) Cecropia pachystachya

1400 mg kg−1 165 & 1650 mg kg−1 600 mg kg−1

Casadebaig et al. (1989)

0 0 0

+ve 0 0

Costus spiralis Achyrocline satureioides Portulaca pilosa

0.5 g kg−1 400 mg kg−1

Digitalis purpurea Visnea mocanera (acetone, methanol, aqueous) Visnea mocanera (chloroform) Visnea mocanera (infusion) Visnea mocanera (syrup) Orthosiphon stamineus Eugenia uniflora Alepidea amatymbica Xylopia aethiopica Piper chaba

Consolini and Migliori (2005) Araujo et al. (1999) Rocha et al. (1994)

R-U/Y/G/n = 24

3h

R-W/Y/O/n = U R-W/Y/G/n = 39

12 h 2h

0 0 0

– 0 0

15 mg kg−1 30 mg kg−1

Navarro et al. (2000)

R-U/Y/IP/n = 16

6h

0 +ve

0 0

0.1–1.0 g kg−1

Hernandez-Perez et al. (1995)

R-W/Y/O/n = 120

6h

−ve

−ve

−ve −ve −ve 0 0

0 0 −ve 0 −ve

0.5 g kg−1 0.25–10 g kg−1 0.25–5.0 g kg−1 700 mg kg−1 15, 60, 120 mg d.l. kg−1 50 mg kg−1 125 mg kg−1 250 mg kg−1 500 mg kg−1

Centaurea phyllocephala Taraxacum officinale (chloroform) Taraxacum officinale (crude, methanol)

0.42 g kg−1 U

Olah et al. (2003) Consolini et al. (1999)

R-W/Y/O/n = 20 R-W/Y/G/n = 6

24 h 3h

Somova et al. (2001)

R-U/Y/O/n = 18

24 h

+ve +ve

0 0

Taufiq-Ur-Rahman et al. (2005)

M-SA/Y/O/n = 15

5h

0

–

0 2

– –

0 0 0

+ve 0

Twaij et al. (1983) Hook et al. (1993)

R-U/Y/IP/n = 7 M-L/Y/O/n = 15

5h 5h

Animal (R, rat; M, mouse) and strain (H, Hafkine; SA, Swiss albino; L, Laca) are defined. PL?, refers to whether a placebo control was included (i.e., yes [Y] or no [N]). How the extract was administered is shown (i.e., G, intra-gastric; IP, intra-peritoneal; O, oral). Duration is the same as defined in previous tables. Other abbreviations used: d.l., dried leaf; U, unclear; ‘+ve’ and ‘-’ represent significant increases and decreases, respectively; ‘0’, no change; and, ‘–’, indicates when a parameter was not measured.

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

Sharafatullah et al. (1986) used anaesthetised animals and collected urine in graduated syringes after 30–40 min. 3 doses were tested with the lowest dose, 13.5 mg kg−1 , having no effect and the two highest doses, 25.9 and 54 mg kg−1 , increased UV by 22.8 and 33.1%. The changes achieved with the highest dose were, in fact, comparable with those seen with 1 mg kg−1 of furosemide (+34.6%). UNa was not measured in this study. Ribeiro et al. (1988) performed conscious rat study. Diuresis was measured via catheterisation of the urinary bladder and exteriorised on the back of the neck. UV was measured for 30 min before intervention and then monitored every 15 min for the subsequent 4 h. Allium sativum was shown to acutely increase UV after 2 (4.2 ml versus 0.9 ml [versus placebo]) and 4 h (5.0 ml versus 1.6 ml). For comparative purposes, the diuretic effects of furosemide (10 mg kg−1 ) and potassiumchloride (≤10 mmol kg−1 l) were similar to those of Allium sativum. Again, effects on UNa were not tested. 3.1.1.4. Conclusion Allium sativum. Studies seem to suggest that Allium sativum may increase UV. At the present time, however, there is a distinct lack of placebo-controlled studies and this must be addressed in order to properly determine whether Allium sativum acts as a diuretic. What is not known is whether Allium sativum really does effect the excretion of sodium or not. This needs further testing. 3.2. Amaranthaceae 3.2.1. Aerva lanata 3.2.1.1. Botanical description. It is an erect herbaceous weed with many branches with spikes (shades ranging from white to pink) that are clustered and range between 1 and 1.5 in. in length (Vetrichelvan and Jegadeesan, 2002; Shirwaikar et al., 2004). It is common in India, Sri Lanka, Arabia, Egypt, Ceylon, tropical Africa, Java and the Philippines (Shirwaikar et al., 2004). 3.2.1.2. Ethnobotany. It is usually prepared as an herbal drink (Udupihille and Jiffry, 1986; Goonaratna et al., 1993). It has traditional uses in Sri Lanka, being commonly prescribed by Ayurvedic doctors, alone or in combination, as a treatment for urinary infections (Attygalle, 1912). This is not its only use, however, as it is suggested to possess analgesic, anthelmintic, anti-inflammatory, anti-malarial, anti-venin, diuretic and sedative properties (Vetrichelvan and Jegadeesan, 2002; Shirwaikar et al., 2004). It is also suggested to be of use in the treatment of bronchitis, coughs, fractures, hematemesis, nasal bleeding, scorpion stings, spermatorrhoea, to clear the uterus after delivery, to prevent lactation and urinary calculi (Selvam et al., 2001; Vetrichelvan and Jegadeesan, 2002; Shirwaikar et al., 2004). 3.2.1.3. Diuretic activity. Three studies, of which two were carried out in humans (Udupihille and Jiffry, 1986; Goonaratna et al., 1993) and one in conscious rats (Selvam et al., 2001). Udupihille and Jiffry (1986) concluded that its leaves and flowers evoked a higher increase in UV than the whole herb itself. Unfortunately, however, this study did not include a placebo group for comparison and no numbers or statistics were reported

13

in the text. The second study (Goonaratna et al., 1993) included a placebo group and showed that Aerva lanata induced changes that did not differ from placebo. The study in rats (Selvam et al., 2001) induced investigated the urolithiatic effects of Aerva lanata over the course of 4 weeks. Ethylene glycol was used to promote the deposition of calcium oxalate crystals and this was used as a model of kidney stone formation. Urinary output along with the excretion of calcium, oxalate, uric acid, phosphorus and protein were all measured. When ethylene glycol was taken alone, 24 h urine volume increased by ∼13 ml, which was similar to the volume excreted (∼10 ml [versus ∼5 ml in the placebo group]) when ethylene glycol and Aerva lanata were ingested together. This finding suggests that Aerva lanata did not have a clear diuretic effect and if anything seemed to reduce urinary output. Urinary excretion of calcium, oxalate, uric acid, phosphorus and protein were all increased by the aforementioned treatment. Although, what the authors did find Aerva lanata reduced urinary calcium and oxalate, when compared with ethylene glycol. Therefore suggesting that Aerva lanata might help reduce the risk of kidney stone formations. 3.2.1.4. Conclusion Aerva lanata. The above studies seem to suggest that Aerva lanata is not a promising diuretic treatment, although it seems to change urinary output with no change in urinary sodium. However, only one study has looked at its effect of urinary sodium excretion and further studies should clarify that Aerva lanata has no natriuretic effect. 3.3. Apiaceae 3.3.1. Foeniculum vulgare 3.3.1.1. Botanical description. Foeniculum vulgare is a glabrous, glaucous perennial or biennial plant growing up to 2.5 cm high. It has 3–4 pinnate leaves that are triangular in shape, long (5–50 mm) and filiform, with acuminate lobes which are cartilaginous at their apex. Its petals are yellow and oblong in shape. The fruit are also oblong, 4–10.5 mm long (Conforti et al., 2006). It is found across Europe (except the north), India, Java, Japan, Egypt, Guatemala and Morocco (Caceres et al., 1987; El Bardai et al., 2001; Conforti et al., 2006). 3.3.1.2. Ethnobotany. Foeniculum vulgare is believed to exert natural analgesic, anti-inflammatory, anti-spasmodic, antidiabetic and antihypertensive effects (Beaux et al., 1997; El Bardai et al., 2001; Conforti et al., 2006). 3.3.1.3. Diuretic activity. Three studies have investigated the diuretic properties of Foeniculum vulgare (Caceres et al., 1987; Beaux et al., 1997; El Bardai et al., 2001). Beaux et al. (1997) used administered a hydroalcohol root extract to saline loaded rats. Two studies were then conducted. The first determined responses to 200 mg kg−1 of Foeniculum vulgare and 10 mg kg−1 of hydrochlorothiazide and compared them with placebo. Both interventions significantly increased UV at 8 h (Foeniculum vulgare, 5.3 ml 100 g−1 versus 4.6 ml 100 g−1 ; hydrochlorothiazide, 5.6 ml 100 g−1 versus 3.9 ml 100 g−1 [versus placebo]) but were no different from placebo after 24 h.

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This change was accompanied by a significant increase in UNa after 8 h (Foeniculum vulgare, ∼0.3 mmol 100 g−1 versus ∼0.2 mmol 100 g−1 ; hydrochlorothiazide, ∼0.4 mmol 100 g−1 versus ∼0.2 mmol 100 g−1 [versus placebo]). In the second part of this study, lower doses were tested (i.e., 25, 50, 100 and 200 mg kg−1 ). Only changes in UV were reported, with the highest 3 doses eliciting similar changes in UV (5.2, 5.0 and 4.6 ml 100 g−1 [200,100 and 50 mg kg−1 ) and the lowest dose having no effect. This data showed also that peak urine flow occurred between 4 and 6 h. Caceres et al. (1987) performed a study in conscious animals and administered a powdered extract of the whole plant which had no effect on UV or UNa. In the third study (El Bardai et al., 2001) a fruit extract was administered daily for 5 days. SHR and WKY rats were studied. The primary objective of this study was to determine an effect on blood pressure. In SHR, systemic blood pressure started to decrease after 2 days of treatment and reached a maximum at day 5 (−12 mmHg as compared with placebo). In WKY, blood pressure maximally decreased on day 2 (−4 mmHg) but then returned to placebo values. A diuretic effect was only seen in SHR, with a peak increase in UV being seen at day 3 (+100%) and UNa increasing by day 5 (1.6 mEq day−1 versus 1.3 mEq day−1 [versus untreated rats]). The authors also showed that Foeniculum vulgare had little effect on the noradrenalin contractile responses of aortic rings, thus suggesting that it worked mainly as a diuretic and natriuretic with little effect on arterial vascular tone.

stimulation of digestion and menstruation; as a carminative; an abortifacient; and may have anti-diabetic and anti-hypertensive properties (Yarnell, 2002; Ozsoy-Sacan et al., 2006; Tahraoui et al., 2007).

3.3.2. Petroselinum sativum (also known as Carum petroselinum and Petroselinum hortense) 3.3.2.1. Botanical description. Petroselinum sativum is a clump-forming biennial herb that grows to around 30 cm high and 60 cm wide. Petroselinum sativum has green leaves that are flat or curly, finely divided and held at the end of long stems. The whole plant has a rounded, almost mound-like appearance. This plant originates from the Mediterranean, is widely distributed in Turkey and is found growing in gardens and fields (Ozsoy-Sacan et al., 2006).

3.3.2.3. Diuretic activity. In the state of S˜ao Paulo, Carum Petroselinum sativum is thought to be able to lower blood pressure (Ribeiro et al., 1988). Ribeiro et al. (1988) prepared an aqueous extract from the seeds of Petroselinum sativum and administered it to rats where it was shown to increase UV after 4 h (5.5 ml versus 1.6 ml [versus placebo]). This was similar to that of furosemide, at a dose of 25 mg kg−1 , which increased UV to 6.0 ml after 4 h. Kreydiyyeh and Usta (2002) also tested the diuretic effects of an aqueous extract prepared from Petroselinum sativum seeds. Urine was collected for 24 h. This was conducted on 2 days, with 1 day serving as placebo and the other day the rats received the extract. Compared with placebo, Petroselinum sativum increased UV (12.8 ml versus 10.9 ml per 24 h [versus placebo]) and the fraction of water intake eliminated as urine (0.40 ml versus 0.34 ml [versus placebo]). The content of sodium in urine was not measured, but the authors did try to elucidate the site of action. This was determined in two ways: using an isolated and perfused kidney; and, Na+ –K+ ATPase activity from a kidney homogenate. The kidney model showed that urinary flow was unaffected by the blockade of sodium channels or NaKCl2 symporters (a type of transport channel found on the ascending loop of Henle) using furosemide or amiloride. When potassium channels were inactivated, however, urine flow was unchanged by Petroselinum sativum and suggests it may work by blocking either potassium absorption or secretion, or may be both, and in keeping with this finding, the authors showed that Petroselinum sativum led to the inhibition of Na+ –K+ pump activity. The result being that K+ secretion and Na+ –K+ absorption would be decreased, which would lead to the accumulation of Na+ and K+ in the lumen of the kidney tubule and this was hypothesised as one of the ways that Petroselinum sativum promotes diuresis. The third study assessed the acute and chronic effects of Petroselinum sativum in acute, volume loaded rats (Lahlou et al., 2006). After 24 h, UV (∼13 ml versus ∼8 ml [versus placebo]) and UNa (139 mmol l−1 versus 89 mmol l−1 [versus placebo]) were significantly increased compared with placebo. In the second part of this trial, the effects of Petroselinum sativum were assessed after 8 days. Findings were in keeping with those shown in the acute trial. However, the authors showed that Petroselinum sativum increased UV on day 1 and reached near maximal effects by day 4, at which time UNa started to increase as compared with placebo. No changes were seen in plasma electrolytes or urinary potassium. These effects are similar to those seen following the administration of furosemide and which led the authors to conclude that Petroselinum sativum acts as a high ceiling diuretic.

3.3.2.2. Ethnobotany. The foliage from Petroselinum sativum is used in cooking as a seasoning and garnish, and also has uses in the pharmaceutical, perfume, and cosmetic industries (Ozsoy-Sacan et al., 2006). It is traditionally used to help the

3.3.2.4. Conclusion Petroselinum sativum. These findings show that Petroselinum sativum is capable of increasing urinary excretion from the body. Two studies have tested the effect of Petroselinum sativum and neither investigated its effects on

3.3.1.4. Conclusion Foeniculum vulgare. These studies provide mixed evidence for Foeniculum vulgare. Again, such differences may be explained by the source of the extract, the rat model used, the method of measuring diuresis (e.g., saline loading versus non-loading), how the extract was administered (i.e., gastrically, Caceres et al., 1987, orally, El Bardai et al., 2001, or intra-peritoneally, Beaux et al., 1997), the dose used (i.e., 25 mg kg−1 , Beaux et al., 1997, to 500 mg kg−1 , Caceres et al., 1987) and the duration (3 h, Caceres et al., 1987, 24 h, Beaux et al., 1997, and 120 h, El Bardai et al., 2001). Future studies need to identify which part of Foeniculum vulgare is active (i.e., fruit, root or the whole plant) and this then needs to be investigated in a controlled study in order to clarify existing studies.

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

UNa. Although, from the conclusions of Kreydiyyeh and Usta (2002), we speculate that Petroselinum sativum may act to promote sodium loss as it has been shown to inhibit Na+ –K+ pump activity in the kidney tubule. Another insight comes from the work of Lahlou et al. (2006). They showed Petroselinum sativum increased UV and electrolyte excretion and may be Petroselinum sativum acts in a similar fashion? Of course these studies clearly show that further studies are now needed to confirm the diuretic effect of Petroselinum sativum and also to elucidate its mechanism of action. 3.4. Asteraceae 3.4.1. Taraxacum officinale 3.4.1.1. Botanical description. It is a perennial weed roughly 15–30 cm in length with large, serrated leaves (5–40 cm in length) clustered in a rosette around the base of the plant. Its flowering stalks stand upright, are 5–40 cm long and carry a solitary terminal inflorescence (Schutz et al., 2006). It is widely distributed in warm temperate areas of the Northern Hemisphere, inhabiting fields and road and railway sides (Schutz et al., 2006).

15

The diuretic activity of crude and partially purified fractions from Taraxacum radix (chloroform, ether and methanol) has been assessed (Hook et al., 1993). The ether fraction is believed to contain ␤-amyrin and ␤-sitosterol, whilst the methanol contains compounds of medium polarity. The Fractions were administered orally and urine was then collected for 5 h. Extracts had no effect on UV, but ether and chloroform extracts did evoke a small, significant increase in UNa (∼6.5 mEq kg−1 versus 3.8 mEq kg−1 after 5 h [extracts versus placebo]). However, this effect was much smaller that than that of furosemide which led to a three-fold increase in UV and an increase in UNa to 13.8 mEq kg−1 after 5 h. This lack of efficacy was taken as evidence that Taraxacum radix contained no organic secondary metabolites with diuretic capabilities. 3.4.1.4. Conclusion Taraxacum officinale. Taraxacum officinale seems capable of modifying UV. Taraxacum folium appears to be more potent than Taraxacum radix and Taraxacum radix may even have a small natriuretic effect (Hook et al., 1993). Presently, further studies to support these effects are needed. 3.5. Brassicaceae

3.4.1.2. Ethnobotany. Taraxacum officinale has traditional uses in Germany, North America, Turkey and China (Schutz et al., 2006). Briefly, in Germany it has been used in the treatment of gout, diarrhoea, blisters, and spleen and liver complaints. In North America, it has been used in kidney disease, dyspepsia and heartburn. In Mexico is suggested to aid the control of Diabetes. In Turkey the herb is applied as a laxative, diuretic and used as an anti-diabetic medicine. In Traditional Chinese Medicine, Taraxacum folium is used to treat hepatitis and upper respiratory tract infections (i.e., bronchitis and pneumonia). Other uses include the treatment of arthritis and rheumatoid arthritis, certain skin conditions (e.g., eczema), weight control (Racz-Kotilla et al., 1974; Hook et al., 1993; Schutz et al., 2006) and as a diuretic. 3.4.1.3. Diuretic activity. The effect of Taraxacum folium (herb) and Taraxacum radix (root) on diuresis and weight loss, in conscious rats, have been compared and investigated previously (Racz-Kotilla et al., 1974). The concentration of the extracts ranged between 0.5 and 6% and effects were assessed on 2 days—days 1 and 30. UV and UNa were assessed using indices of diuretic and sodium excretion (i.e., the ratio of responses to placebo). This comparison showed that the herb had more marked effects that the root both acutely (diuretic index, 1.9 versus 1.4; and, sodium saliuretic index, 6.3 versus 2.6) and chronically (diuretic index, 2.1 versus 1.7; and, sodium saliuretic index, 4.0 versus 1.3). Numbers on days 1 and 30 seem to be similar, although this was not equivocal as no statistics were provided. The authors did provide a comparison by looking at responses to 80 mg kg−1 of furosemide (the diuretic index was 1.9 and the sodium saliuretic index was 7.9), again suggesting responses with the herb were similar to those achieved with the furosemide. In the second part of this study, diuretic effects were coupled with the measurement of changes in body weight and led the authors to conclude that diuresis may be one mechanism explaining decreases in body weight.

3.5.1. Lepidium latifolium and Lepidium sativum 3.5.1.1. Botanical description. Lepidium latifolium is a perennial plant growing to between 30 cm and even as tall as 2 m. This plant has woody stems, waxy leaves and small white flowers arranged in clusters. The plant produces fruits in the form of two reddish seeds and roughly measures 1.6 mm in diameter. Lepidium sativum is a perennial plant and eaten as a garnish. Lepidium is native to southern Europe (Navarro et al., 1994; Jouad et al., 2001a; Maghrani et al., 2005b; Tahraoui et al., 2007). Lepidium latifolium, but not Lepidium sativum, is also native to Asia and nowadays can be found growing in the wild across North America. 3.5.1.2. Ethnobotany. The Lepidium latifolium has traditional uses as anti-escrobte, stomach tonic, aperitif and diuretic (Navarro et al., 1994; Martinez et al., 2004). In Morocco, Lepidium sativum is considered a herbal medicine and recommended in the treatment of hypertension, diabetes and renal disease (Jouad et al., 2001a; Maghrani et al., 2005b; Tahraoui et al., 2007). 3.5.1.3. Diuretic activity. Navarro et al. (1994) determined the urinary effects of an aqueous leaf extract (from Lepidium latifolium) over a 6 h period. When given intra-gastrically, UV increased (∼60 ml kg−1 versus ∼40 ml kg−1 [versus placebo]) but UNa and potassium were unchanged. These effects were seen at two doses (50 mg kg−1 and 100 mg kg−1 ). The authors also tested the responses following the intra-peritoneal injection of Lepidium. This time, only the highest dose increased UV (∼50 ml kg−1 versus ∼40 ml kg−1 [versus placebo]). Interestingly, it also increased the excretion of potassium (∼60 mEq l−1 versus ∼40 mEq l−1 [versus placebo]). This data show that Lepidium was more potent when given orally and that this route does not negatively effect potassium excretion. In another study,

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Maghrani et al. (2005b) administered an aqueous extract, from the seeds of Lepidium sativum, to both normal or hypertensive rats for 3 weeks. The primary goal was to assess an effect on blood pressure. In spontaneously hypertensive rats (SHR), systolic blood pressure was lowered (∼178 mmHg) as compared with placebo (∼189 mmHg) after 3 weeks of intervention. The reference drug (irbesartan, an angiotensin-II blocker) had even more marked effects, with systolic blood pressure being ∼154 mmHg after 3 weeks. No changes were seen in the normotensive, Wistar-Kyoto rats (WKY). The secondary objective was to determine whether UV and UNa changed. In WKY, UV was ∼23 ml 24 h−1 which was significantly elevated compared with placebo (∼19 ml 24 h−1 ) and similar to that achieved with irbesartan (∼23 ml 24 h−1 ). In the SHR group, Lepidium had no effect compared with control. Analysis of urinary electrolytes showed Lepidium increased UNa in both WKY (∼2.2 compared to ∼1.3 24 h−1 in the placebo treatment) and SHR models (∼1.0 compared to ∼0.6 24 h−1 seen with placebo). Again, effects were similar to those induced by irbesartan (∼1.8 and ∼1.2 24 h−1 in SHR and WKY groups, respectively). In both groups of animals Lepidium increased the excretion of potassium and chloride in urine. These findings suggest that Lepidium works as an anti-hypertensive agent when blood pressure is elevated, but has little or no effect in normotension. Lepidium does seem to work as a diuretic, increasing both UV and electrolytes in normotensive rats. There is one other point that needs considering. In the normotensive rats, UV increased after the first week of treatment; however, UNa did not reach significance until week 3. Hence, there is some disparity in the timing of their onset which may have been missed if this study had lasted 1 week. In the spontaneously hypertensive rats, it seems to work only as a natriuretic as UNa was significantly elevated after 2 weeks of treatment, but there was no effect on UV during intervention. 3.5.1.4. Conclusion Lepidium latifolium and Lepidium sativum. The current evidence seems confusing. One study was acute (24 h) and showed an increase in UV with no change in UNa (Navarro et al., 1994). The other study lasted 3 weeks and showed a natriuretic, as indicated by increased UNa, and diuretic effect (increased UV) which was seen in normotensive but not hypertensive rats. These observations raise two issues—the effect of duration and the animal model used. Another difference relates to the type of extract used (i.e., leaf versus seed) and the dosage [20–100 mg kg−1 , Maghrani et al., 2005b, versus 50–100 mg kg−1 , Navarro et al., 1994]. It seems that further studies are needed and they must address whether the genus Lepidium does have diuretic properties and by what mechanism they work. 3.6. Caprifoliaceae 3.6.1. Sambucus mexicana and Sambucus nigra 3.6.1.1. Botanical description. The genus Sambucus contains between 5 and 30 species of fast-growing shrubs and small trees growing that grow to less than 10 m high. Its leaves are serrated and arranged in opposition to one another in a pinnate with

5–9 leaflets that are 5–30 cm in length and around 3–5 cm in width. In late Spring Sambucus flowers and this is followed the production of bunches of small red, bluish or black berries that are 3–5 mm in diameter. The genus Sambucus is found in temperate to subtropical regions of the Northern and Southern Hemispheres, with its distribution being more widespread in the Northern than Southern Hemisphere (Anon., 2005). 3.6.1.2. Ethnobotany. Sambucus nigra is consumed in preserves, wine and juice, and is recognised as potentially having health benefits owing to its antioxidant and antiviral properties, and immune system modulation via cytokines (Anon., 2005). Thus, areas in which Sambucus nigra has been postulated as beneficial include diabetes, lipid lowering and protection against vital infections such as HIV, influenza and herpes simplex (Anon., 2005). In complete contrast, Sambucus mexicana is not as commercialised and not considered for its medicinal properties (Thole et al., 2006). 3.6.1.3. Diuretic activity. Beaux et al. (1999) tested the leaves from Sambucus nigra and Caceres et al. (1987) used an ethanol extract of Sambucus Mexicana. Both species are used in traditional medicines although the actives are unclear and could involve di- and tri-terpene, glycosides and phenols (e.g., flavanoids, tannins and coumarins) (Caceres et al., 1987). Beaux et al. (1999) conducted a trial in conscious rats to test the acute diuretic effects of four extracts (one of which was Sambucus nigra). They showed that UV reached a peak at 6 h. The cumulative volume at 8 and 24 h was 6.0 and 7.5 ml 100 g−1 (+1.4 and +1.1 ml 100 g−1 greater than placebo, respectively) and UNa at these time points was ∼0.3 and ∼0.4 mmol 100 g−1 . This was significantly greater than placebo (∼0.2 mmol 100 g−1 ) and not so different from hydrochlorothiazide (10 mg kg−1 ) which significantly increased UV (5.6 ml 100 g−1 and 7.1 ml 100 g−1 ) and UNa (∼0.4 mmol 100 g−1 and ∼0.5 mmol 100 g−1 ) at 8 and 24 h, respectively. The second trial used the results from an ethnobotanical survey to identify plants used for urinary ailments in Guatemala (Caceres et al., 1987). From an initial 250 plants, 67 were tested in four independent trials and one of these Sambucus Mexicana. This was prepared as an ethanol extract (500 mg kg−1 ) and administered nasogastrically. UV was collected for 6 h and responses compared with placebo and hydrochlorothiazide (25 mg kg−1 ). In contrast to the European variety (Beaux et al., 1999), however, responses of UV were no different from placebo. 3.6.1.4. Conclusion Sambucus mexicana and Sambucus nigra. Many differences are seen in the aforementioned studies. For instance, they used different species; administered the extract via different routes (intra-peritoneally, Caceres et al., 1987 versus nasogastrically Beaux et al., 1999); and used different extraction methods (aqueous, Caceres et al., 1987 versus ethanol, Beaux et al., 1999). Neither of these studies constructed doseresponse curves and this should also be considered in future studies.

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3.7. Cecropiaceae 3.7.1. Cecropia leucocoma and Cecropia pachystachya 3.7.1.1. Botanical description. Cecropia is a genus with roughly 25 species of trees. Cecropia is identified by its large, circular palmate lobed leaves that are between 30 and 40 cm in width and deeply divided into 7–11 lobes. In northeast Argentina, Paraguay and southern Brazil, Cecropia pachystachya can reach heights of around 10 m with large, dual coloured leaves that are dark-green on their upper-side and silver-grey on their underside. In central Argentina, Cecropia pachystachya is not as tall and reaches heights of less than 1 m (Consolini and Migliori, 2005). This tree can is found in the forests of neotropical regions in paranaense phytogeographical province in Northeast Argentina, Paraguay and southern Brazil, and the temperate hilly grasslands of central Argentina (Consolini and Migliori, 2005; Consolini et al., 2006).

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in width and about 5–15 cm in height. Its leaves are arranged in a rosette and between 8 and 40 mm in length. Its flowers are a rose-purple colour and 3–4.5 mm in length. This plant originates from Asia and Europe (Jouad et al., 2001b,c). 3.8.1.2. Ethnobotany. Spergularia purpurea is documented as being used in traditional Moroccan medicine and a water extract is prepared from the whole plant and used in the treatment of renal disease, hypotension and diabetes (Jouad et al., 2001a).

3.8. Caryophyllaceae

3.8.1.3. Diuretic activity. Jouad et al. (2001b) administered Spergularia purpurea, furosemide (10 mg kg−1 ) and a placebo to normal rats and measured UV and urinary electrolytes every week for 4 weeks. Data showed significant increases in UV with Spergularia purpurea and were seen after 1 week of intervention and sustained till week 4 (∼23 ml 24 h−1 with 400 mg kg−1 of Spergularia purpurea). After 4 weeks of treatment, responses seemed to be dose-dependent (16.9 and 19.3 ml 24 h−1 with doses of 100 and 200 mg kg−1 of Spergularia purpurea, respectively), were similar to those of furosemide (∼23 ml 24 h−1 ) and were significantly greater than placebo (∼10 ml 24 h−1 ). Changes in urinary electrolytes (sodium, potassium and chloride) mirrored those of UV, with the highest dose increasing UNa to ∼4 mEq kg−1 as compared with placebo (∼1.5 mEq kg−1 ). Again, this change was not too dissimilar to that achieved with furosemide (∼3 mEq kg−1 ). Jouad et al. (2001b) measured electrolytes in plasma and showed no changes with Spergularia purpurea. Furthermore, effects on glomerular filtration were measured. At the lowest and highest doses (100 and 400 mg kg−1 ) filtration increased relative to placebo, but was unchanged by the intermediate dose. Thus, different doses would seem to elicit differing responses and we could speculate that the increase in glomerular filtration might reflect a passive response to a change in blood pressure. In the second study by Jouad et al. (2001c), the flavonoids from Spergularia purpurea (5 mg kg−1 ) were extracted and effects on blood pressure and renal function determined over a 7 day period. The extract was administered daily to normotensive and hypertensive rats, and compared with placebo and furosemide (10 mg kg−1 ). In both animal models furosemide and Spergularia purpurea flavonoids decreased blood pressure to a similar magnitude but did not differ significantly from placebo. These flavonoids also interfered with the tubular absorption of electrolytes as shown by significant increases in UNa, potassium and chloride. Indeed, UV and UNa increased to ∼60 ml kg−1 24 h−1 and ∼10–15 mEq kg−1 24 h−1 , respectively, in those receiving flavonoids. These effects were roughly double those seen in the placebo group (∼30 ml kg−1 24 h−1 and ∼7.5 mEq kg−1 24 h−1 ) and were similar to responses seen with furosemide. From visual inspection of the graphs it also seems apparent that electrolyte excretion seemed to be greater in normotensive rats and this was especially true for the excretion of potassium.

3.8.1. Spergularia purpurea 3.8.1.1. Botanical description. This is a glabrous or pubescent plant that inhabits sandy soil with a stem that is around 2–2.5 cm

3.8.1.4. Conclusion Spergularia purpurea. The present studies imply that Spergularia purpurea acts as a diuretic by interfering with the tubular absorption of water and electrolytes. These

3.7.1.2. Ethnobotany. Cecropia pachystachya is a traditional medicine and used as a dietary supplement, a treatment for coughs and asthma, a cardiotonic and as a diuretic (Consolini et al., 2006). Indeed, studies in rats show it may lower blood pressure and this could be explained by diuresis (Consolini and Migliori, 2005). The traditional use of Cecropia leucocoma is not so well described. Although, we are led to believe that in the state of S¨ao Paulo in Brazil it is a medicinal plant popularly used for its diuretic and hypertensive properties (Ribeiro et al., 1988). 3.7.1.3. Diuretic activity. Cecropia leucocoma (Ribeiro et al., 1988) was administered to rats implanted with a urinary catheter. UV was collected for 4 h after its administration and shown to increase, compared with a placebo control, after 30, 120 and 240 min. Indeed, at the end of the recording phase UV was 5.5 ml in the treatment group and 1.6 ml in the placebo group. The second trial explored the cardiovascular effects of Cecropia pachystachya (Consolini and Migliori, 2005) and showed a lowering of steady state blood pressure with extracts obtained from neotropical and temperate regions. However, the mechanism for this lowering was not via diuresis as UV and urinary sodium and potassium after 3 h was unchanged by Cecropia pachystachya. 3.7.1.4. Conclusion Cecropia leucocoma and Cecropia pachystachya. The studies suggest that Cecropia leucocoma may work as a diuretic, but that Cecropia pachystachya does not. However, these are the only two studies to have assessed the diuretic effects of plants from the genus Cecropia and further studies may consider confirming the effect of Cecropia leucocoma on urinary excretion and combining this with measurements of UNa. Moreover, it may be worthwhile assessing the effect of varying doses as only one dose was tested (Ribeiro et al., 1988).

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effects seem dose dependent and are seen after 1 week and sustained. Moreover, the active for this change may actually be the flavanoids as they had similar effects to the extract on UV and UNa. Blood pressure may partly explain such effects as glomerular filtration tended to be increased by Spergularia purpurea. Hence, further studies confounding the present observations are needed in order to support the use of Spergularia purpurea as a natural diuretic. 3.9. Cucurbitaceae 3.9.1. Cucumis melo and Cucumis trigonus 3.9.1.1. Botanical description. Cucumis melo is oval in shape, measures up to around one foot in length, has smooth skin interspaced by length-wise grooves. Cucumis trigonus, like Cucumis melo, is a fruit and resembles a small egg streaked with yellow and green, and is extremely bitter. Cucumis melo is found Worldwide and Cucumis trigonus can be located in North India. 3.9.1.2. Ethnobotany. Cucumis trigonus (Naik et al., 1981) and Cucumis melo (Singh and Sisodia, 1970) are from the Cucurbitaceae family. In India the seeds from Cucumis melo are produced to provide a sweet edible oil that has nutritional value and analgesic, anti-inflammatory (Naik et al., 1980; Vouldoukis et al., 2004) and diuretic properties (Singh and Sisodia, 1970). In contrast, Cucumis trigonus (Naik et al., 1981) has no traditional usage, but the alcohol extract contains a glycoside fraction which, via its anti-inflammatory properties, may promote diuresis. 3.9.1.3. Diuretic activity. The diuretic effect of Cucumis trigonus (Naik et al., 1981) was tested in conscious albino rats and the study included a placebo group and a positive test group (i.e., hydrochlorothiazide). After oral administration, UV was measured for 6 h. The accumulated volume was then tested for its sodium, chloride and potassium content, and pH. Two doses (25 and 50 mg kg−1 ) of Cucumis trigonus significantly increased UV (+165 and +212% from placebo, respectively) as did hydrochlorothiazide (+253%). Average UNa was also increased by these treatments: Cucumis trigonus (25 mg kg−1 ), 147; Cucumis trigonus (50 mg kg−1 ), 153; hydrochlorothiazide (25 mg kg−1 ), 161; and, placebo, 132 mEq l−1 . This data suggests that Cucumis trigonus has similar effects to those of hydrochlorothiazide and works like a clinical diuretic drug. Singh and Sisodia (1970) prepared an extract from the seeds of Cucumis melo. Anaesthetised dogs were volume loaded and the ureters were cannulated for the collection of urine. Once urine output had stabilised the extracts were given intravenously. At the same time, creatinine and chloride were measured in urine and blood (at 0, 15 and 30 min) to assess their renal clearances. An ether extract of Cucumis melo significantly increased UV (151 ml versus 96 ml [versus baseline]) and its chloride content (114 mEq l−1 versus 95 mEq l−1 [versus baseline]). The authors investigated the mechanism for this increase in chloride and showed that glomerular filtration rate increased (90 versus 61 unknown units [versus baseline]) and that its tubular

reabsorption was decreased (as shown using the renal stop flow technique). Similar effects are also achieved with mercurial and xanthine diuretics and this study concluded that Cucumis melo acted in a similar fashion, although no comparison with such drugs was performed. 3.9.1.4. Conclusion Cucumis melo and Cucumis trigonus. These studies used different species from the genus Cucumis, but both extracts were shown to significantly increase UV. They also showed increases in urinary chloride excretion, which may be due to the extract interfering with absorption in the renal tubule (Naik et al., 1981). The present trials suggest that plant and seed extracts from the genus Cucumis may have diuretic capabilities and this would seem to warrant further research in order to address its efficacy. 3.10. Equisetaceae 3.10.1. Elephantopus scaber 3.10.1.1. Botanical description. Elephantopus scaber is a shrub that grows in the wild. It grows to a height of between 20 and 40 cm, has a high rosette of leaves. Its leaf stems are very short, white, hairy and can be found close to the ground. Elephantopus scaber is a small herb that grows in hotter regions of India (Avani and Neeta, 2005) and throughout America. 3.10.1.2. Ethnobotany. Elephantopus scaber has a wide range of reported uses in traditional medicine. Indeed, it has been used as an analgesic, anti-emetic, anti-inflammatory, anti-microbial. It has been used in conditions such as bronchitis, smallpox, diarrhoea and suggested to have cytotoxic and anti-tumoral properties (Laranja et al., 1991; Avani and Neeta, 2005; Xu et al., 2006). 3.10.1.3. Diuretic activity. Two studies have tested its diuretic properties; ine in conscious rats (Poli et al., 1992) and the other in a human trial (Laranja et al., 1991). Poli et al. (1992) gave Elephantopus scaber to conscious rats and showed no effect on UV after 3 h. Its effect on UNa not tested. The authors looked at a number of additional physiological processes that included toxicity, analgesic activity, anti-pyretic and anti-inflammatory activities, intestinal transit times and arterial blood pressure. When given intravenously it was reported to decrease arterial blood pressure as well as heart rate. Oral administration was not tested. It was also shown to be quite toxic, with an LD50 of 2 and 6 mg kg−1 when given intra-peritoneally and orally, respectively, and it had mixed effects on intestinal transit times; times were decreased by an aqueous extract and increased by a hydro-alcoholic extract. The second study was an acute, placebo-controlled trial (6 h) in 10 subjects (Laranja et al., 1991). The results of this study supported those of Poli et al. (1992) as UV and urinary, and plasma, electrolytes (i.e., calcium, phosphate, uric acid, sodium and potassium) were unchanged. 3.10.1.4. Conclusion Elephantopus scaber. These studies provide little support that Elephantopus scaber works as a

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diuretic. As in other studies, no dose-response curves were constructed. So, whether diuresis can be achieved with higher doses, than those tested in these studies, still remains unclear.

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from the difference between liquid intake and UV. Equisetum bogotense significantly decreased the water balance (the net loss was 496 ml) and increased UNa (+65 from 157 mEq l−1 ). This was accompanied by significant increases in urinary potassium and chloride.

3.11. Equisetaceae 3.11.1. Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum 3.11.1.1. Botanical description. Equisetum is a genus of perennial plants that reproduce by spores rather than seeds. Plants normally grow to between 0.2 and 1.5 m high, although some reach more considerable heights (e.g., Equisetum giganteum can grow up to 5 m and Equisetum myriochaetum can reach 8 m, Andrade-Cetto and Heinrich, 2005). The leaves of these plants are thick and bushy and the stems are hollow, jointed, and have ridges. This genus is near-cosmopolitan and is only absent from Australasia and Antarctica. All Equisetum species are herbaceous perennials and can be found in temperate (e.g., Equisetum hiemale) and tropical regions. Equisetum giganteum is native to southern and central America and found in hot, humid environments. In contrast, Equisetum fluviatile is found in the Northern Hemisphere and grows in shallow watery areas like marshes and streams. 3.11.1.2. Ethnobotany. In Chile and Mexico, Equisetum has traditional uses as a diuretic and a means of treating kidney stones. It has also been used for polishing copper utensils, cleansing teeth (Perez Gutierrez et al., 1985; Lemus et al., 1996) and to have anti-diabetic (Andrade-Cetto and Heinrich, 2005) and platelet sedating effects (Mekhfi et al., 2004). 3.11.1.3. Diuretic activity. Two studies (Perez Gutierrez et al., 1985; Lemus et al., 1996) have tested the effects of Equisetum. Perez Gutierrez et al. (1985) tested four species of Equisetum—Equisetum fluviatile, Equisetum hiemale var. affine, Equisetum giganteum and Equisetum myriochaetum. Extracts were prepared in distilled water and administered orally. Urine was then collected every 2 h over a 6 h period. All species increased UV after 6 h with the largest change being observed with Equisetum hiemale var. affine (9.0 ml versus 2.9 ml [versus placebo]) and the smallest with Equisetum giganteum (5.0 ml versus 2.9 ml [versus placebo]). For comparison, hydrochlorothiazide (25 mg kg−1 ) was administered and was not so different (7.1 ml). Analysis of urinary electrolytes showed a similar trend. Indeed, with Equisetum hiemale var. affine and Equisetum giganteum, UNa was 161.7 and 147.0 mEq l−1 (versus 110.0 mEq l−1 achieved with placebo). In the group receiving hydrochlorothiazide, UNa was 160.0 mEq l−1 . The data also showed that Equisetum had similar effects on urinary potassium and chloride excretion, and it was suggested to act in a fashion to hydrochlorothiazide. The second study also reported positive effects with Equisetum. This was a clinical trial in humans in which a 10% solution of Equisetum bogotense (equivalent to 0.75 g day−1 ) was given for 2 days. Urine was collected for 24 h on the second day and water balance was assessed

3.11.1.4. Conclusion Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum. Studies show that the genus Equisetum has positive effects on UV and UNa, and would seem to support its diuretic and natriuretic effect. However, the human trial did not include a placebo control with the point being that more controlled trials are still needed. 3.12. Euphorbiaceae 3.12.1. Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus 3.12.1.1. Botanical description. Phyllanthus is suggested to be made up of some 750 species and comprise trees, bushes, and annual or biennial herbs (Hnatyszyn et al., 1999). Phyllanthus amarus is an annual, glabrous herb that grows to between 30 and 60 cm. Its stems are angular with distichously, elliptic-oblong shaped leaves and its flowers are yellow and numerous. Its fruits are capsule shaped, very small and smooth and its seeds are longitudinally ribbed on the back. Phyllanthus corcovadensis and Phyllanthus sellowianus are closely related to Phyllanthus niruri in appearance, phytochemical structure and history of use but the difference is that they are found in drier tropical climates. In appearance, they are small erect annual herbs growing to between 30 and 40 cm in height. They have alternately arranged leaves with each leaf being oval-elliptic in shape, having a small projecting tip, a greenish-white in colour, having no petals and being glabrous. Individual flowers occur on flower stalks and are star-shaped and their fruits are small capsule shaped, green and glabrous (Jones, 2007). Phyllanthus is found in tropical areas, although it is found in subtropical regions and is usually quite scattered in its distribution (Unander et al., 1990; Jones, 2007). 3.12.1.2. Ethnobotany. Traditional uses vary from place to place, but Phyllanthus has been medicinally to treat urolithiasis (Calixto et al., 1984; Freitas et al., 2002), as an anti-hypertensive (Ribeiro et al., 1988), an anti-diabetic (Srividya and Periwal, 1995), an analgesic (Gorski et al., 1993), a treatment for liver diseases (Dhiman and Chawla, 2005), as an anti-viral agent (Martin and Ernst, 2003), as a laxative and anti-septic (Hnatyszyn et al., 1999). 3.12.1.3. Diuretic activity. Phyllanthus corcovadensis (Ribeiro et al., 1988) and Phyllanthus sellowianus (Hnatyszyn et al., 1999) have been assessed in rats. Phyllanthus sellowianus was given at a dose of 400 mg kg−1 and changes in UV and urinary electrolytes were monitored for the subsequent 8 h. UV was shown to be significantly increased compared to a placebo control (3.6 ml versus 2.7 ml), as was UNa which was 178 mEq l−1 (versus 136 achieved with the placebo). Urinary potassium and chloride were measured and a significant increase in the latter

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was reported. Comparisons were also made with hydrochlorothiazide which increased UV 2 h after it was given. In bladder cannulated rats, Phyllanthus corcovadensis (Ribeiro et al., 1988) was also shown to increase UV (5.9 ml versus 1.6 ml [versus placebo]) 4 h after its administration. Significant increases were also seen after 2 h. This study did not, however, measure changes in urinary electrolytes. The third study was conducted in 40–60 year old subjects and they were asked to ingest Phyllanthus amarus for 10 days (Srividya and Periwal, 1995). At the end of this period blood pressure was measured and urine was collected for 24 h. A control group was included, but this is an unreliable comparison as only 5 subjects were recruited and they were not matched (i.e., age and blood pressures) with the treatment group. Both UV (2.4 l versus 1.5 l) and UNa (26.1 mEq l−1 versus 19.1 mEq l−1 ) were shown to be significantly increased in the treatment group, but this finding is confounded by the higher blood pressures in this group which would have influenced urinary output.

stamineus. Urine was collected for 24 h and peak changes were shown to occur between 5 and 6 h after administration. At 8 h (5.9 100 g−1 versus 3.9 100 g−1 [versus placebo]) and 24 h (6.9 ml 100 g−1 versus 5.7 ml 100 g−1 [versus placebo]) UV was significantly elevated compared to placebo. UNa was not changed (0.26 mmol g−1 and 0.38 mmol g−1 at 8 and 24 h, respectively). In another study (Olah et al., 2003), 50 or 70% ethanol was used to extract two tinctures of Orthosiphon stamineus and were shown to increase UV (41.9 and 28.9 ml 24 h−1 kg−1 [50 and 70%, respectively]) and UNa (5.7 and 4.6 mEq 24 h−1 kg−1 ). However, no statistical analyses were reported and this was taken as evidence that responses were no different from placebo (32.4 ml 24 h−1 kg−1 and 3.6 mEq 24 h−1 kg−1 ). Doan et al. (1992) conducted a trial in humans looking at the acute (within 1 day) effects of Orthosiphon stamineus. In this trial food and water intake was standardised. Urine was collected at 8 am and served as a control, and then was measured every 2 h between until 10 pm. However, no significant changes were in UV or UNa were found.

3.12.1.4. Conclusion Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus. Phyllanthus may have diuretic and natriuretic effects, although caution should be aired when interpreting the findings from the human clinical trial as this was not very well designed and so whether the findings from the animal trials can be translated to humans still remains to be determined.

3.13.1.4. Conclusion Orthosiphon stamineus. On this evidence, Orthosiphon stamineus does not act like a clinical diuretic drug as only one study (Beaux et al., 1999) demonstrated a significant increase in UV with no change in UNa, and the remaining studies reported no effects (Doan et al., 1992; Englert and Harnischfeger, 1992; Olah et al., 2003). 3.14. Oleaceae

3.13. Lamiaceae 3.13.1. Orthosiphon stamineus 3.13.1.1. Botanical description. Orthosiphon stamineus comes from little oval, green leaves that are finely toothed and rolled like ordinary tea. Orthosiphon stamineus is an herb that is found growing in tropical areas and is popular medicinal plant in Southeast Asia where it is consumed as an herbal tea (Doan et al., 1992; Beaux et al., 1999; Olah et al., 2003). 3.13.1.2. Ethnobotany. Orthosiphon stamineus is traditionally used to treat hypertension, diabetes, urinary disorders, rheumatism, tonsillitis and menstrual disorders (Englert and Harnischfeger, 1992; Beaux et al., 1997; Matsubara et al., 1999; Sriplang et al., 2007). It is also documented in the German Pharmacopoeia DAB 9 and considered effective in humans by the Commission E of the Federal Health Authority (BGA) (Englert and Harnischfeger, 1992; Matsubara et al., 1999). 3.13.1.3. Diuretic activity. Three trials have been conducted in rats. Englert and Harnischfeger (1992) tested the diuretic effect of a mixture of leaves and stems from Orthosiphon in conscious, volume loaded rats. UV was unchanged by this intervention, but UNa increased (∼2-fold, compared with placebo, at a dose of 750 mg kg−1 ), as did urinary potassium (∼2-fold) and chloride (∼3-fold). However, no statistics were reported and for this reason we scored these effects as not being significantly different and conclude Orthosiphon stamineus had no effect. Beaux et al. (1999) also looked at its diuretic effects of Orthosiphon

3.14.1. Fraxinus excelsior 3.14.1.1. Botanical description. Fraxinus excelsior is a deciduous tree capable of growing between 20 and 35 m tall. Its leaves are arranged in a pinnate fashion, are usually between 20 and 35 cm in length and are clustered in groups of 9–13. It can be found in forests, parks and gardens across middle European temperate zones (e.g., northern Spain, the British Isles, France, central Europe, and southern Scandinavia) (Hemmer et al., 2000). It is also a native shrub widely distributed throughout the southeastern region of Morocco (Eddouks et al., 2005). 3.14.1.2. Ethnobotany. Fraxinus excelsior is suggested to be an analgesic, anti-inflammatory, anti-oxidant, anti-rheumatic and anti-pyretic, and to have hypoglycaemic (Maghrani et al., 2004; Eddouks et al., 2005). 3.14.1.3. Diuretic activity. Two studies have investigated its diuretic effects in conscious rats (Casadebaig et al., 1989; Eddouks et al., 2005). Casadebaig et al. (1989) looked at the acute (4 h) effects of alcoholic and aqueous spray dried powders. The aqueous extract had no significant effect on UV and tended (P = 0.07) to increase UNa (0.11 ± 0.03 mEq versus 0.08 ± 0.02 mEq [lowest dose versus placebo]). The alcohol-based spray had no effect on UV and (at the highest dose) significantly increased UNa (0.14 ± 0.03 mEq versus 0.08 ± 0.02 mEq [treatment versus placebo]). An aqueous extract was employed in the second study (Eddouks et al., 2005)

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and was administered to rats for 3 weeks. In spontaneously hypertensive rats (SHR), UV increased significantly at weeks 1 and 2 with a peak change at week 1 (∼18.3 ml 24 h−1 versus ∼10.8 ml 24 h−1 [versus placebo after 1 week]). This was accompanied by significant increases in UNa with a peak change occurring at week 2 (∼1.0 mmol 24 h−1 versus ∼0.8 mmol 24 h−1 [versus placebo]) and significant increases being seen at all weeks. In Wistar-Kyoto rats (WKY), UV significantly increased at weeks 2 and 3, with the peak effect seen at week 3 (∼27.8 ml 24 h−1 versus ∼18.0 ml 24 h−1 [versus placebo]). UNa reached a maximum (∼1.8 mmol 24 h−1 versus ∼1.2 mmol 24 h−1 [versus placebo]) at week 1 and was maintained through to week 3. 3.14.1.4. Conclusion Fraxinus excelsior. One study showed no effect with an aqueous extract of Fraxinus excelsior and significant increases in UNa with an alcohol extract (Casadebaig et al., 1989). The second trial showed an aqueous extract increased both UNa and UV (Eddouks et al., 2005). At first glance this evidence would seem to be inconsistent; however, this may be partly explained by the number of extent of differences between the 2 trials. For instance, the type of extract (aqueous versus alcoholic); the animal model (Wistar, WKY and SHR); and, differing doses tested. Indeed, in both studies an aqueous decoction was used. One study reported a positive increase at a dose of 20 mg kg−1 and the second showed no effect at a dose of 1650 mg kg−1 . Therefore, further studies are needed in order to define whether Fraxinus excelsior does, or does not, work as a diuretic. 3.15. Malvaceae 3.15.1. Hibiscus sabdariffa 3.15.1.1. Botanical description. Hibiscus sabdariffa is an annual or perennial herb or woody-based sub-shrub that grows to around 2 m tall. Its leaves are lobed, roughly 8–15 cm in length and are alternately arranged along a stem. The flowers of Hibiscus sabdariffa are 8–10 cm across, have a whitish-yellow appearance and a dark red spot at the base of each petal. At the base of the petals there is a stout fleshy red calyx (∼1.5–2 cm in width) which brightens as the fruit matures. Hibiscus sabdariffa is a tropical plant and can be found growing across West Africa (Odigie et al., 2003; Onyenekwe et al., 1999). 3.15.1.2. Ethnobotany. Various parts of the plant (flower, leaves, calyx and corolla) are prepared as a drink or for medicinal purposes (Herrera-Arellano et al., 2004). Indeed, its leaves are commonly used as a diuretic, sedative and refrigerant, and its fruits are considered to be an anti-scorbutic. Its calyces are commonly prepared as a drink and used as a mild diuretic, a colorectal, an intestinal anti-septic, a mild laxative, as an aid in heart and nerve conditions, to lower blood pressure and to treat calcified arteries (Onyenekwe et al., 1999; Ajay et al., 2007). 3.15.1.3. Diuretic activity. Several studies have assessed its diuretic capabilities. Odigie et al. (2003) assessed its effects on blood pressure in renovascular hypertensive rats. Six weeks

21

after surgery rats received an aqueous Hibiscus sabdariffa petal extract for 8 weeks. Rats were compared with sham-operated rats and a placebo group. At the end of intervention, blood pressure in the hypertensive rats receiving Hibiscus sabdariffa and sham-operated rats was similar (mean arterial pressures were 109 and 107 mmHg [Hibiscus sabdariffa and sham-operated rats]), but lower than the pressure in those rats ingesting placebo (147 mmHg). No difference in heart rate was seen between these groups. Rats were then anaesthetised and the urinary bladder cannulated. Urine was collected for 90 min and no effect was evidence as determined by the lack of differences between groups. Onyenekwe et al. (1999) conducted an interventional trial in which an aqueous extract from Hibiscus sabdariffa calyces was given to spontaneously hypertensive rats for 3 weeks. The primary objective in this study was blood pressure. In the normal group no change was observed and in the hypertensive group, systolic and diastolic blood pressures were shown to be lower than placebo (systolic blood pressure, 135 mmHg versus 153 mmHg [versus placebo]; and, diastolic blood pressure, 89 mmHg versus 70 mmHg). In the spontaneous rats receiving Hibiscus sabdariffa, UV was significantly increased compared with placebo (5.0 cm3 day−1 versus 3.9 cm3 day−1 [versus placebo]) and unchanged in the normotensive group. However, when the difference between water intake and UV was calculated, the data seem to imply that Hibiscus sabdariffa changed body water balance in hypertensive and normotensive rats (water balance was ∼5.0–5.0 cm3 day−1 in those ingesting Hibiscus sabdariffa and 8.5 cm3 day−1 those administered placebo). The third animal trial assessed the excretion of urine and its electrolytes (Ribeiro et al., 1988). After administration of an aqueous decoction of Hibiscus sabdariffa calyces, urine was collected for 6 h and was increased to 103 ml kg−1 . This was significantly higher than that achieved with a water placebo (46 ml kg−1 ) and similar to that following the ingestion of 25 mg kg−1 of hydrochlorothiazide (83 ml kg−1 ). UNa was significantly increased (6.5 mEq kg−1 versus 2.7 mEq kg−1 [versus placebo]) and, again, this change was similar to responses with hydrochlorothiazide (4.2 mEq kg−1 ). Urinary potassium and uric acid were also increased by Hibiscus sabdariffa. Only 1 human trial has been conducted with Hibiscus sabdariffa calyces (Herrera-Arellano et al., 2004). Hypertensive patients were recruited and aged between 30 and 80 years of age. 10 grams of Hibiscus sabdariffa was consumed with 0.5 l of water and ingested, at breakfast, for 4 weeks. Responses were measured on the first and last day of the trial, and compared with captopril (25 mg, twice a day). Hibiscus sabdariffa decreased systolic and diastolic blood pressure by 14 and 11 mmHg, respectively, which did not differ significantly from those responses with captopril (−16 and 13 mmHg, respectively). Assessment of urinary parameters showed that chloride, potassium and pH were unchanged by Hibiscus sabdariffa. In addition to these, UNa was shown to increase significantly (+19, from 106 mEq l−1 24 h−1 ). How these changes compared with captopril was not determined. 3.15.1.4. Conclusion Hibiscus sabdariffa. The current studies provide mixed evidence for Hibiscus sabdariffa with two

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studies showing it increased UNa (Caceres et al., 1987; Herrera-Arellano et al., 2004). Its effects on UV are less clear. Caceres et al. (1987) reported an increase, Odigie et al. (2003) no change, Onyenekwe et al. (1999) showed an effect but only when hypertensive rats were used. Going on this evidence further studies are needed to clarify the effect of animal strains on measured responses; to determine concurrent changes in urine excretion and solute output; to establish the acute (i.e., hours) and chronic (days) effect of Hibiscus sabdariffa. 3.16. Oleaceae 3.16.1. Olea europaea 3.16.1.1. Botanical description. Olea europaea is an evergreen tree or shrub that is around 8–15 m in height. Its leaves are silver-green, oblong in shape and measure 4–10 cm in length and 1–3 cm in width. It has a trunk that is gnarled and twisted and it has a drupe shaped fruit that is 1–2.5 cm in length. Olea europaea is native to Europe, Asia and Africa (Somova et al., 2003) and cultivated for its fruit and oil. 3.16.1.2. Ethnobotany. Olea europaea has traditional uses as a diuretic, anti-hypertensive, emollient, febrifuge, a tonic for urinary and bladder infections and headaches, and in cardiovascular disease (Ribeiro et al., 1988; Jouad et al., 2001a; Somova et al., 2003; Tahraoui et al., 2007). 3.16.1.3. Diuretic activity. Somova et al. (2003) investigated the diuretic effects of Olea europaea which was cultivated in African, Greece or Christ town. Ursolic acid and oleanolic acid were also tested. Urine was collected at 5 and 24 h after intraperitoneal application of the various extracts. Urea (1 g kg−1 ) and hydrochlorothiazide (25 mg kg−1 ) were used as a placebo and positive control, respectively. In general, the data showed that none of the extracts induced effects different from urea. There were a few exceptions. Indeed, after 5 h the saliuretic index (sodium plus potassium) was decreased by oleanolic acid (376 mmol l−1 versus 440 mmol l−1 , respectively); and the carbonic anhydrase activity (taken as chloride divided by sodium plus) was decreased by ursolic acid (0.47 mmol l−1 versus 0.65 mmol l−1 ) and the wild African cultivated Olea europaea (0.50 mmol l−1 ) as compared with urea. When compared with hydrochlorothiazide, however, effects with Olea europaea or its actives were markedly diminished after 5 and 24 h. Ribeiro et al. (1988) prepared an ethanol extract from the leaves of Olea europea and this was administered orally. UV was collected at 15, 30, 45, 60, 120 and 240 min and shown to be no different from placebo. 3.16.1.4. Conclusion Olea europaea. Leaf extracts evoked no changes in diuresis or natriuresis. Whether their actives have diuretic effects need further attention (i.e., oleanolic acid, Alvarez et al., 2002, 2003; Somova et al., 2003 and polyphenols, Singh et al., 2007). Studies should also address the effect of differing doses.

3.17. Poaceae 3.17.1. Imperata cylindrica 3.17.1.1. Botanical description. Imperata cylindrica grows up to 3 m high and has leaves that are roughly 2 cm wide, which narrow to a point at their tips. The leaf edges are fine toothed and embedded with sharp silica crystals. The dorsal surface of the leaf is hairy whilst the ventral side is not. Imperata cylindrica is a perennial rhizomatous grass native to south-east Asia. It can be found in humid tropics, but has spread to warm temperate zones worldwide. Indeed, in 1911 it was accidentally introduced to the United States of America and can now be found in Florida, parts of Alabama, Georgia, Louisiana, and Mississippi, and South Carolina (King and Grace, 2000). 3.17.1.2. Ethnobotany. In Thailand and Vietnam, Imperata cylindrica is deemed a medicinal plant by the Vietnamese Ministry of Health (Doan et al., 1992). 3.17.1.3. Diuretic activity. Sripanidkulchai et al. (2001) prepared an aqueous extract from the root of Imperata cylindrica and fed it to adult Sprague-Dawley rats. UV was collected for 4 h. No changes in UNa were observed and assessment of UV showed a general retention of water (15.6 ml versus 26.3 ml [the highest dose versus placebo]). The second study also used a root extract. This was a randomised, placebo designed cross-over trial in healthy volunteers (Doan et al., 1992). The study was conducted in 40 subjects (2 cohorts of 20 subjects) and lasted 4 days. On the first day subjects reported to the laboratory and provided blood samples for the measurement of haemoglobin, creatinine, sodium and potassium. The second and fourth days served as intervention days and the third was treated as a washout day. On intervention days, subjects were monitored in the test facility and dietary intake was restricted. UV was collected every morning at 8 a.m. and prior to any intervention. It was then collected for 24 h and measured after 14 h, respectively. None of the interventions tested changed UV or UNa (or its electrolytes). 3.17.1.4. Conclusion Imperata cylindrica. The present studies would seem to suggest that Imperata cylindrica, given alone or in combination with other traditional medicines (Doan et al., 1992), does not function as a diuretic. If anything, Imperata cylindrica led to an acute decrease in UV and this reflects a net retention of water by the body. How this extract affects other cardiovascular functions is as yet unclear and perhaps needs addressing to identify potentially undesirable effects. 3.17.2. Zea mays 3.17.2.1. Botanical description. Zea mays grows annually and has a distinctive growth form with the lower leaves being quite broad (50–100 cm in length and 5–10 cm width). Its stems grow to around 2 m high with many nodes and branching leaves. It is under these leaves, close to the stem where the ears grow. The ear, when ripe, is made up of edible grains that are organised in rows around a white pithy substance. Each ear is estimated to

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contain something like 200–400 grains and is around 10–25 cm in length. Zea mays was originally domesticated in Mesoamerica and then spreading throughout the American continents and the rest of the world following European contact with the Americas. 3.17.2.2. Ethnobotany. Zea mays has a wide range of traditional uses and has been suggested to act as an anti-hypertensive, to have anti-diabetic properties, to help in the treatment of renal disease and to help pass stones from the kidney and urinary tract, and to treat benign prostate hyperplasia, cystitis, gout and nephritis (Ribeiro et al., 1988; Doan et al., 1992; Jouad et al., 2001a; Maksimovic et al., 2004; Andrade-Cetto and Heinrich, 2005; Tahraoui et al., 2007). 3.17.2.3. Diuretic activity. Ribeiro et al. (1988) showed UV was significantly increased 6 h after its ingestion (5.7 ml versus 1.6 ml [versus placebo]). Al Ali et al. (2003) looked at effects after 24 h and failed to show any change in UV or UNa as compared with placebo. It was, however, shown to increase the excretion of potassium and chloride. Maksimovic et al. (2004) determined effects of a 5 and 10% decoction of Zea mays over an 8 day period. The average increase in UV was 210% by the 5% decoction (versus 119% with placebo), with the peak change being observed on day 1 (∼250%) and being no different from placebo on day 4 (∼145%). Interestingly, UV was unchanged with the 10% decoction. Mean UNa was increased by both doses (94 and 85 mmol l−1 with 5 and 10% decoctions, respectively) as compared with placebo (58 mmol l−1 ). These effects were seen after 1 day of treatment and were generally sustained throughout the course of the intervention phase. Both doses led to mean increases in urinary potassium, urea and chloride (only seen with the 5% decoction), glomerular filtration rate and urine pH. Plasma electrolytes were also measured and decreases were found in sodium and chloride after 8 days. No changes in serum potassium, urea and creatinine were evident. In contract, only 1 human study has been conducted (Doan et al., 1992). This was a randomised, cross-over designed study in 40 volunteers. Urine was collected for 24 h on 4 consecutive days—the first day was a control recording; days 2 and 3 were intervention days; and, the third day served as a wash-out between study days. Disappointingly, no changes in UV and urinary electrolytes were found. 3.17.2.4. Conclusion Zea mays. These studies do not seem to support the notion of Zea mays being a diuretic. In animals, one study found no changes in UV or UNa (Al Ali et al., 2003), another found positive effects that were only evident at low doses (Maksimovic et al., 2004) and the remaining trial showed an increase in UV but did not assess changes in UNa (Ribeiro et al., 1988). From reviewing these studies, it is clear that the intervention period differed and this may provide some explanation for inconsistencies between their findings. However, the lack of effect in humans (see Doan et al., 1992) raises questions as to the duration of intervention was sufficient, whether the dose was high enough to elicit measurable

23

responses and whether the source had any bearing on the study outcomes. 3.18. Urticaceae 3.18.1. Urtica dioica 3.18.1.1. Botanical description. Urtica dioica grows up to 2 m high during the summer months and dies down during the winter. It has leaves that are soft and serrated at their edges. They are roughly 3–15 cm in length and have a cordate base and an acuminate tip. Brittle, hollow, silky hairs cover the leaves and stems and contain formic acid which serves as a defence. Urtica dioica is an herbaceous flowering plant that is native to Africa, Asia, Europe and North America. 3.18.1.2. Ethnobotany. This plant has traditional uses as an anti-inflammatory, to stimulate the proliferation of human lymphocytes, and as a therapy against prostate enlargement (Tahri et al., 2000; Yarnell, 2002). Urtica dioica is also reported to be an anti-diabetic medicine in Mexico and Morocco (Jouad et al., 2001a; Andrade-Cetto and Heinrich, 2005), as an antihypertensive in Morocco (Jouad et al., 2001a, via promotion of diuresis, Caceres et al., 1987] and to treat urinary ailments in Guatemala (Caceres et al., 1987; Koch, 2001). In Turkey Urtica dioica has a wide variety of additional uses that include anaemia, pruritus, cancer, obesity, stomach aches and rheumatism (Uzun et al., 2004). 3.18.1.3. Diuretic activity. Two studies have tested the diuretic effects of Urtica dioica. In the first study (Caceres et al., 1987), Urtica dioica was one of 67 plants investigated for its purported diuretic effects (based on its frequency of use and its availability). The authors, however, failed to show any change in UV up to 6 h after administration and owing to this lack of efficacy changes in urinary solute excretion were not tested. The second study was in anaesthetised rats (Tahri et al., 2000). Blood pressure was measured in the femoral artery and the bladder was cannulated for urine collection. A placebo group was not included and so changes were compared to the baseline. Urtica dioica was infused for 60 min at doses of 4 and 24 mg−1 kg−1 and decreased arterial blood pressure by 17 and 43 mmHg, respectively (from 114 mmHg). The change at the highest dose being not too dissimilar to that achieved with 2 mg−1 kg−1 of furosemide (−31 mmHg). Concurrent increases in urinary flow and UNa were also documented. Again, the highest dose producing similar increases in urinary flow (+9.1 ␮l min−1 versus 9.6 ␮l min−1 from a baseline of ∼11 ␮l min−1 [highest dose of Urtica dioica versus furosemide]) and sodium excretion (+1.0 and 1.1 ␮Eq min−1 ) to that of furosemide. Increases in both parameters were seen at the lowest dose, but they were less marked (+1.2 ␮l min−1 and 0.2 ␮Eq min−1 , respectively). This data would suggest that Urtica dioica, when directly infused, has dilatatory effects on arterial tone and acts as a diuretic and natriuretic. 3.18.1.4. Conclusion Urtica dioica. Based on this evidence, Urtica dioica would seem to act as a diuretic/natriuretic when

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given intra-venously. When high doses were given orally (1 g kg−1 ) no effect was found, however. Whether changes in the excretion of UNa were changed in this latter study remain unclear. At the present time this data would not seem to support the use of Urtica dioica as a traditional diuretic and there is a need for further studies.

showed an increase in UNa that would seem to be around half that seem with a clinical diuretic.

3.19. Zygophyllaceae

Table 5 shows that of the extracts reviewed the majority have been performed in conscious animals and relatively few have had their efficacy confirmed in humans. This is one consideration that we do not acknowledge in our efficacy rating. In fact, only 8 extracts have been tested in a human clinical trial and they seem to generally support findings in animals. However, this is clearly one area that needs further investigation as findings in animals need to be translated to humans in order for a natural extract to be recommended for traditional use as a diuretic. The design of trials also needs some attention. Some extracts may appear to be potentially interesting, but it must be pointed out that not all trials have been designed in the same manner. Some may be criticised for lacking a placebo control group or comparison with a known diuretic. Other considerations that need to be mentioned are that the type of extract tested was not always the same (i.e., seed, fruit, and leaves) and this can influence recorded responses. Some studies failed to measure UV and UNa and this missing information makes it difficult to determine whether the extract does act as a diuretic or not. There was also some variation in the duration and doses used, which again makes comparisons between trials difficult. A further issue that needs to be addressed is whether some of these extracts are safe for human consumption (Foote and Cohen, 1998) when taken alone or with other foods or drugs. Studies also lack information on the site of action within the kidney (Materson, 1983; Puschett, 1994) and what effects they have on the vasculature.

3.19.1. Tribulus terrestris 3.19.1.1. Botanical description. Tribulus terrestris is an herbaceous perennial plant growing as a summer annual in colder climates. Its stems branch from its crown to a width between 10 and 100 cm, and are usually flat in appearance. Its leaves are pinnate and quite short (∼0.5 in length). Tribulus terrestris is characterised by small (4–10 mm wide) yellow petal flowers and thorny fruits. These latter fruits yield 4–5 seeded nuts which are hard and have 2 sharp spines (10 mm in length by roughly 5 mm in width). Tribulus terrestris is widely distributed in Africa, Southern Europe, China, Japan, Korea and western parts of Asia (Al Ali et al., 2003; Sharifi et al., 2003). 3.19.1.2. Ethnobotany. In Ayurvedic medicine, the fruits of Tribulus terrestris are recommended for the treatment of urinary disorders and in traditional Chinese medicine it has been used as an anti-hypertensive, coronary heart disease and to treat erectile dysfunction by increasing serum testosterone levels (Sharifi et al., 2003). It is also suggested to stimulate melanocyte proliferation and therefore is a putative treatment for vitiligo and it is reputed to have anti-bacterial and cytotoxic activities (Singh and Sisodia, 1971; Al Ali et al., 2003). 3.19.1.3. Diuretic activity. In anaesthetised dogs, Singh and Sisodia (1971) tested the effects of an ether and aqueous extract from the fruit of Tribulus terrestris. Urine flow was significantly increased by the ether extract (37–52 ml [versus baseline]) but not by the aqueous extract. The ether extract was also shown to increase glomerular filtration (as shown by a significant increase in creatinine clearance). It did not have any effect on urinary chloride and changes in UNa were not measured. Al Ali et al. (2003) tested the effect of an aqueous Tribulus terrestris decoction prepared from its fruit and leaves. Urine was collected for the 24 h after administration and shown to increase UV (5.6 ml versus 16.2 ml) and UNa (0.5 ml versus 0.7 mEq l−1 ) compared with placebo. These effects were similar to responses achieved with a 120 mg kg−1 dose of furosemide (15.6 ml 24 h−1 and 1.3 mEq l−1 24 h−1 ). The authors showed that Tribulus terrestris also significantly increased potassium and chloride excretion. Tribulus terrestris was then applied to the Guinea pig ileum which led to dose-wise contractions. Such an effect on ureter tone was hypothesised as being capable of propelling stones from the urinary tract. 3.19.1.4. Conclusion Tribulus terrestris. These studies show that Tribulus terrestris acts as an aquaretic as it only increased UV. Whether it has a natriuretic effect remains to be confirmed as one study did not investigate this effect whereas the other

4. Discussion 4.1. Future needs for this area of research

4.2. Limitations The current article only deals with articles published in English and this ignores a large volume of studies published in other languages. In assessing diuresis our criteria were that urine volume and UNa had to change concurrently and that there had to be multiple publications in order for it to be considered potentially interesting. Of course by doing so we ignore those single studies that report positive effects, however, we have captured the design characteristics and responses in such studies (see Tables 2–5) but feel that the lack of clinical trials did not warrant further attention. The present format will permit their inclusion should new evidence arise in the hear future. Furthermore, we used combined changes in UV and sodium excretion to indicate efficacy. The rationale for doing so is that these measures mean it is possible to make comparisons with diuretic drugs used in a clinical setting. Such comparisons enable researchers to draw conclusions about the physiological relevance of such extracts (i.e., could changes be used and make a significant difference?) and to draw conclusions about how they act within the kidney (i.e., do they have the same effects on the composition of urine as clinically used diuretics?).

Table 5 Summary of those studies (where there was more that one) and effects on urinary volume (UV) and urinary sodium excretion (UNa) Extract

Aerva lanate

Study model Human (UV/UNa)

Animal Conscious (UV/UNa)

+ve/– (Udupihille and Jiffry, 1986), 0/0 (Goonaratna et al., 1993)

+ve/– (Selvam et al., 2001)

Allium sativum

0/0 (Laranja et al., 1991)

Comments

Low

Studies suggest Aerva lanate might work as a diuretic with no effect on natiuresis. Although, this latter effect needs further corroboration in controlled human intervention trials Most studies have been conducted in acute animal studies and show no real effects. Such evidence does not seem to warrant further trials at the present time The single study in humans showed little effect on diuresis and natriuresis although questions still remain relating to the effect of higher doses Evidence for a diuretic effect with Foeniculum vulgare seems mixed at the present time and this relates to a number of factors that have contributed to these studies, including: dose; the animal model used; the method and time at which diuresis was measured; and, the route of administration These studies are conflicting and require further clarification. Such studies need to construct dose-response curves; determine the effect of different extract preparations; and, account for the possible effect of differing animal models This evidence is again mixed and studies are needed to assess diuretic and natiuretic effects are measured concurrently, and the effect of acute and chronic ingestion of Hibiscus sabdariffa Imperata cylindrica would not seem to act as a diuretic as it had no effect on diuresis or natriuresis Studies have only assessed urinary output and shown no effect. These have, however, not determined effects on urinary sodium excretion or the effect of differing doses

Animal Anaesthetised (UV/UNa)

+ve/– (Sharafatullah et al.,1986), 0/0 (Pantoja et al., 1996), 0/0 (Pantoja et al., 1991)

Low

0/– (Poli et al., 1992)

Low

Foeniculum vulgare

0/0 (Caceres et al., 1987), +ve or 0/+ve or 0 (El Bardai et al., 2001), +ve or 0/+ve or – (Beaux et al., 1997)

Medium

Fraxinus excelsior

0/0 (Casadebaig et al., 1989), +ve/+ve (Eddouks et al., 2005)

Medium

Hibiscus sabdariffa

–/+ve (Herrera-Arellano et al., 2004)

+ve/+ve (Caceres et al., 1987), +ve or 0/– (Onyenekwe et al., 1999)

Imperata cylindrica

0/0 (Doan et al., 1992)

−ve/0 (Sripanidkulchai et al., 2001)

Low

0/– (Ribeiro et al., 1988), 0/– (Somova et al., 2003)

Low

Olea europaea

0/– (Odigie et al., 2003)

Medium

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Elephantopus scaber

+ve/– (Ribeiro et al., 1988)

Efficacy rating

25

26

Table 5 (Continued ) Extract

Study model

Efficacy rating

Comments

Only one study showed an increase in urinary volume with this extract and the remainder showed little effect, which suggests Orthosiphon stamineus does not have diuretic capabilities The current evidence is quite positive with all studies showing an improvement in urinary output. However, only one study measured urinary sodium excretion and this should be confirmed in further studies to suggest its use as a natural diuretic Both studies showed promising effects on urinary output and sodium excretion. These effects may be explained by the flavanol content of Spergularia purpurea. Further studies are now needed in humans Taraxacum officinale is not a promising diuretic owing to its lack of concurrent effects on urinary excretion. However, studies can be criticised for their design and lack of comparison and so they do not fully address the issue of whether Taraxacum officinale is or is not a diuretic Only one study shows Tribulus terrestris to have a natriuretic effect. This needs to be confirmed in order to suggest its use as a natural diuretic This evidence here was judged as being low as no effect was seen in conscious animals when Urtica dioica was given orally. Studies are now needed to clarify diuretic status of this extract The main finding here is a lack of effect in humans with mixed effects being seen in conscious animals. The effect of higher doses was not rigorously tested and this may be considered in future human trials

Animal Conscious (UV/UNa)

0/0 (141)

+ve/0 (Beaux et al., 1999), 0/0 (Olah et al., 2003), 0/0 (Englert and Harnischfeger, 1992)

Low

Petroselinum sativum

+ve/– (Kreydiyyeh and Usta, 2002), +ve/– (Ribeiro et al., 1988), +ve/+ve (Lahlou et al., 2006)

Medium

Spergularia purpurea

+ve/+ve (Jouad et al., 2001c), +ve/+ve (Jouad et al., 2001b)

High

Taraxacum officinale

0/+ve (Hook et al., 1993), 0/0 (Racz-Kotilla et al., 1974)

Low

Tribulus terrestris

+ve/+ve (Al Ali et al., 2003)

+ve/– (Singh and Sisodia, 1971)

Medium

Urtica dioica

0/– (Caceres et al., 1987)

+ve/+ve (Tahri et al., 2000)

Low

Orthosiphon stamineus

Zea mays

0/0 (Doan et al., 1992)

0/0 (Al Ali et al., 2003), +ve/– (Ribeiro et al., 1988), +ve or 0/+ve (Maksimovic et al., 2004)

Animal Anaesthetised (UV/UNa)

Low

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Human (UV/UNa)

Genus Cecropia (Cecropia leucocoma and Cecropia pachystachya)

+ve/– (Ribeiro et al., 1988), 0/0 (Consolini and Migliori, 2005)

Genus Cucumis (Cucumis melo and Cucumis trigonus)

+ve/+ve (Naik et al., 1981)

+ve/+ve (Lemus et al., 1996)

Genus Phyllanthus (Phyllanthus amarus, Phyllanthus corcovadensis and Phyllanthus sellowianus)

+ve/+ve (Srividya and Periwal, 1995)

Genus Sambucus (Sambucus mexicana and Sambucus nigra)

+ve/– (Singh and Sisodia, 1970)

Medium

+ve/+ve (Perez Gutierrez et al., 1985)

High

+ve/0 (Navarro et al., 1994), +ve or 0/+ve (Maghrani et al., 2005b)

Medium

+ve/– (Ribeiro et al., 1988), +ve/+ve (Hnatyszyn et al., 1999)

Medium

0/0 (Caceres et al., 1987), +ve/+ve (Beaux et al., 1999)

Medium

Two species from the Genus Cecropia were tested and provided mixed results. Studies now need to repeat these experiments to confirm the reported effects The genus Cucumis seems to have diuretic capabilities. What is still in question is whether it has natriuretic effects The present evidence seems very promising as effects have been seen in humans and conscious animals and with a wide variety of species from this genus These studies assessed changes acutely and chronically which makes their comparison difficult. In addition to this, the species differed and so studies are needed to corroborate the current findings The positive finding in humans seems quite promising, however, this study was not very well controlled. Studies supporting an effect in humans is still lacking and needs further investigation The European variety of Sambucus was shown to act as a diuretic, whereas the Mexican variety had no effects. However, this was not the only difference as the routes of administration differed, as did the extraction methods. Thus, studies confirming these findings are still needed

Responses are shown as being indifferent (0), significantly increasing (+ve) or decreasing (−ve). ‘–’ indicates that this was not measured. A rating of low, medium or high was assigned to studies and is used as a representative measure of efficacy for particular extracts. Please refer to Tables 2–4 for an over-view of the study designs.

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

Genus Equisetum (Equisetum bogotense, Equisetum fluviatile, Equisetum giganteum, Equisetum hiemale var. affine and Equisetum myriochaetum) Genus Lepidium (Lepidium latifolium and Lepidium sativum)

Low

27

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4.3. Conclusions The current review is intended to provide an overview of the current knowledge surrounding the use of herbal medicines as diuretics. Indeed, there are more than a 100 extracts purporting diuretic effects (see Table 1). From these we identified 21 extracts reporting concurrent effects on UV and UNa (Materson, 1983; Puschett, 1994; Foote and Cohen, 1998; Reyes and Taylor, 1999; Brater, 2000) and summarised these into 3-categories of efficacy (high, medium or low; see Table 5). Extracts which we regard as being potentially the most efficacious include species belonging to the genus Equisetum and Spergularia purpurea as having a high level of efficacy. Others include Foeniculum vulgare, Fraxinus excelsior, Hibiscus sabdariffa, Petroselinum sativum, and species belong to the genus Cucumis, Lepidium, Phyllantus and Sambucus. So what is the relevance of the current findings? We think the present findings are of interest where herbal medicines are used according to folklore. This is extremely important and potentially very useful in countries that have limited resources for the production and importation of modern medicines (Doan et al., 1992) as they are accessible, cheap and applicable to the local population. Our evidence is also of potential use in generating monographs and recommendations on their use (Englert and Harnischfeger, 1992; Laranja et al., 1991). Another areas where the current knowledge can be applied include the substantiation of marketed products (e.g., Urol mono® ; Leuschner, 1995), where the evidence can be quite limited. The last issue for us to raise here is whether these results are relevant to the wider population? We have already outlined that diuretics are used to lower blood pressure in hypertension. What we have not dealt with is the safety of natural medicines when ingested for long periods, such as in the treatment of chronic diseases like hypertension. Indeed, some of the extracts we reviewed are recommended for acute disorders like urinary tract infections rather than ongoing diseases (see Table 1). This would also be required to compile monographs and recommendations for such extracts. In a clinical setting, we speculate that these extracts could, one day, offer another possible treatment to existing drug regimes. One benefit could be the offer of a more natural treatment or milder effects and fewer side effects. Milder effects are quite interesting as they could offer a first line of therapy or as an add-on to conventional medicines as their lower potency could improve tolerance to more potent drugs. References Adam, O., Wolfram, G., 1984. Effect of different linoleic acid intakes on prostaglandin biosynthesis and kidney function in man. American Journal of Clinical Nutrition 40, 763–770. Afzal, M., Khan, N.A., Ghufran, A., Iqbal, A., Inamuddin, M., 2004. Diuretic and nephroprotective effect of Jawarish Zarooni Sada—a polyherbal unani formulation. Journal of Ethnopharmacology 91, 219–223. Agunu, A., Abdurahman, E.M., Andrew, G.O., Muhammed, Z., 2005. Diuretic activity of the stem-bark extracts of Steganotaenia araliacea hochst [Apiaceae]. Journal of Ethnopharmacology 96, 471–475. Ajay, M., Chai, H.J., Mustafa, A.M., Gilani, A.H., Mustafa, M.R., 2007. Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces. Journal of Ethnopharmacology 109, 388–393.

Al Ali, M., Wahbi, S., Twaij, H., Al Badr, A., 2003. Tribulus terrestris: preliminary study of its diuretic and contractile effects and comparison with Zea mays. Journal of Ethnopharmacology 85, 257–260. Alvarez, M.E., Maria, A.O., Saad, J.R., 2002. Diuretic activity of Fabiana patagonica in rats. Phytotherapy Research 16, 71–73. Alvarez, M.E., Maria, A.O., Villegas, O., Saad, J.R., 2003. Evaluation of diuretic activity of the constituents of Clematis montevidensis Spreng. (Ranunculaceae) in rats. Phytotherapy Research 17, 958–960. Andallu, B., Radhika, B., 2000. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Indian Journal of Experimental Biology 38, 607–609. Andrade-Cetto, A., Heinrich, M., 2005. Mexican plants with hypoglycaemic effect used in the treatment of diabetes. Journal of Ethnopharmacology 99, 325–348. Anon., 2005. Monograph: Sambucus nigra (elderberry). Alternative Medicine Review 10, 51–54. Araujo, V.T., Diogo, D.C., Silva Monteiro, A.P., Riggio Lima-Landman, M.T., Lapa, A.J., Souccar, C., 1999. Evaluation of the antiurolithiatic activity of the extract of Costus spiralis Roscoe in rats. Journal of Ethnopharmacology 66, 193–198. Armstrong, L.E., Pumerantz, A.C., Roti, M.W., Judelson, D.A., Watson, G., Dias, J.C., Sokmen, B., Casa, D.J., Maresh, C.M., Lieberman, H., Kellogg, M., 2005. Fluid, electrolyte, and renal indices of hydration during 11 days of controlled caffeine consumption. International Journal of Sport Nutrition and Exercise Metabolism 15, 252–265. Attygalle, J., 1912. Singhalese Materia Medica. Colombo Apothecaries Ltd. Press. Avani, K., Neeta, S., 2005. A study of the antimicrobial activity of Elephantopus scaber. Indian Journal of Pharmacology 37, 126–127. Beaux, D., Fleurentin, J., Mortier, F., 1997. Diuretic action of hydroalcohol extracts of Foeniculum vulgare var dulce (D.C.) roots in rats. Phytotherapy Research 11, 320–322. Beaux, D., Fleurentin, J., Mortier, F., 1999. Effect of extracts of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L. and Arctostaphylos uva-ursi (L.) Spreng. in rats. Phytotherapy Research 13, 222–225. Benjumea, D., Abdala, S., Hernandez-Luis, F., Perez-Paz, P., Martin-Herrera, D., 2005. Diuretic activity of Artemisia thuscula, an endemic Canary species. Journal of Ethnopharmacology 100, 205–209. Bergman, E.A., Massey, L.K., Wise, K.J., Sherrard, D.J., 1990. Effects of dietary caffeine on renal handling of minerals in adult women. Life Science 47, 557–564. Bevevino, L.H., Aires, M.M., 1994. Effect of crude extract of roots of Bredemeyera floribunda Willd. II. Effect on glomerular filtration rate and renal tubular function of rats. Journal of Ethnopharmacology 43, 203–207. Biswas, S., Murugesan, T., Maiti, K., Ghosh, L., Pal, M., Saha, B.P., 2001. Study on the diuretic activity of Strychnos potatorum Linn. seed extract in albino rats. Phytomedicine 8, 469–471. Brater, D.C., 2000. Pharmacology of diuretics. American Journal of the Medical Sciences 319, 38–50. Caceres, A., Giron, L.M., Martinez, A.M., 1987. Diuretic activity of plants used for the treatment of urinary ailments in Guatemala. Journal of Ethnopharmacology 19, 233–245. Caceres, A., Saravia, A., Rizzo, S., Zabala, L., De Leon, E., Nave, F., 1992. Pharmacologic properties of Moringa oleifera. 2: Screening for antispasmodic, antiinflammatory and diuretic activity. Journal of Ethnopharmacology 36, 233–237. Calixto, J.B., Yunes, R.A., Neto, A.S., Valle, R.M., Rae, G.A., 1984. Antispasmodic effects of an alkaloid extracted from Phyllanthus sellowianus: a comparative study with papaverine. Brazilian Journal of Medical and Biological Research 17, 313–321. Camargo, M.E., Berdeja, B., Miranda, G., 2004. Diuretic effect of the aqueous extract of Bidens odorata in the rat. Journal of Ethnopharmacology 95, 363–366. Carbajal, D., Casaco, A., Arruzazabala, L., Gonzalez, R., Tolon, Z., 1989. Pharmacological study of Cymbopogon citratus leaves. Journal of Ethnopharmacology 25, 103–107.

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31 Casadebaig, J., Jacob, M., Cassanas, G., Gaudy, D., Baylac, G., Puech, A., 1989. Physicochemical and pharmacological properties of spray-dried powders from Fraxinus excelsior leaf extracts. Journal of Ethnopharmacology 26, 211–216. Conforti, F., Statti, G., Uzunov, D., Menichini, F., 2006. Comparative chemical composition and antioxidant activities of wild and cultivated Laurus nobilis L. leaves and Foeniculum vulgare subsp. piperitum (Ucria) coutinho seeds. Biological and Pharmaceutical Bulletin 29, 2056–2064. Consolini, A.E., Baldini, O.A., Amat, A.G., 1999. Pharmacological basis for the empirical use of Eugenia uniflora L. (Myrtaceae) as antihypertensive. Journal of Ethnopharmacology 66, 33–39. Consolini, A.E., Migliori, G.N., 2005. Cardiovascular effects of the South American medicinal plant Cecropia pachystachya (ambay) on rats. Journal of Ethnopharmacology 96, 417–422. Consolini, A.E., Ragone, M.I., Migliori, G.N., Conforti, P., Volonte, M.G., 2006. Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on isolated rat hearts and conscious mice. Journal of Ethnopharmacology 106, 90–96. Dhiman, R.K., Chawla, Y.K., 2005. Herbal medicines for liver diseases. Digestive Diseases and Sciences 50, 1807–1812. Doan, D.D., Nguyen, N.H., Doan, H.K., Nguyen, T.L., Phan, T.S., van Dau, N., Grabe, M., Johansson, R., Lindgren, G., Stjernstrom, N.E., 1992. Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus). Journal of Ethnopharmacology 36, 225–231. Eddouks, M., Maghrani, M., Zeggwagh, N.A., Haloui, M., Michel, J.B., 2005. Fraxinus excelsior L. evokes a hypotensive action in normal and spontaneously hypertensive rats. Journal of Ethnopharmacology 99, 49–54. El Bardai, S., Lyoussi, B., Wibo, M., Morel, N., 2001. Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat. Clinical and Experimental Hypertension 23, 329–343. Englert, J., Harnischfeger, G., 1992. Diuretic action of aqueous Orthosiphon extract in rats. Planta Medica 58, 237–238. Foote, J., Cohen, B., 1998. Medicinal herb use and the renal patient. Journal of Renal Nutrition 8, 40–42. Freitas, A.M., Schor, N., Boim, M.A., 2002. The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU International 89, 829–834. Fujitsuka, N., Goto, K., Takeda, S., Aburada, M., 2004. The diuretic effect of Sairei-to is mediated by nitric oxide production in pentobarbital-anesthetized rats. Journal of Pharmacological Sciences 94, 185–191. Galati, E.M., Tripodo, M.M., Trovato, A., Miceli, N., Monforte, M.T., 2002. Biological effect of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. Note I: diuretic activity. Journal of Ethnopharmacology 79, 17–21. Galati, E.M., Trovato, A., Kirjavainen, S., Forestieri, A.M., Rossitto, A., Monforte, M.T., 1996. Biological effects of hesperidin, a citrus flavonoid (Note III): antihypertensive and diuretic activity in rat. IL Farmaco 51, 219–221. Gallagher, M., Perkovic, V., Chalmers, J., 2006. Diuretics: a modern day treatment option? Nephrology 11, 419–427. Ganapaty, S., Dash, G.K., Subburaju, T., Suresh, P., 2002. Diuretic, laxative and toxicity studies of Cocculus hirsutus aerial parts. Fitoterapia 73, 28–31. Godfraind, T., 2006. Calcium-channel modulators for cardiovascular disease. Expert Opinion on Emerging Drugs 11, 49–73. Goonaratna, C., Thabrew, I., Wijewardena, K., 1993. Does Aerva lanata have diuretic properties? Indian Journal of Physiology and Pharmacology 37, 135–137. Gorski, F., Correa, C.R., Filho, V.C., Yunes, R.A., Calixto, J.B., 1993. Potent antinociceptive activity of a hydroalcoholic extract of Phyllanthus corcovadensis. Journal of Pharmacy and Pharmacology 45, 1046–1049. Grover, J.K., Yadav, S., Vats, V., 2002. Medicinal plants of India with antidiabetic potential. Journal of Ethnopharmacology 81, 81–100. Haloui, M., Louedec, L., Michel, J.B., Lyoussi, B., 2000. Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea. Journal of Ethnopharmacology 71, 465–472. Hemmer, W., Focke, M., Wantke, F., Gotz, M., Jarisch, R., Jager, S., Gotz, M., 2000. Ash (Fraxinus excelsior)-pollen allergy in central Europe: specific role

29

of pollen panallergens and the major allergen of ash pollen Fra e 1. Allergy 55, 923–930. Hernandez-Perez, M., Sanchez-Mateo, C.C., Darias, V., Rabanal, R.M., 1995. Effects of Visnea mocanera extracts on the bleeding time, gastrointestinal transit and diuresis in rodents. Journal of Ethnopharmacology 46, 95–100. Herrera-Arellano, A., Flores-Romero, S., Chavez-Soto, M.A., Tortoriello, J., 2004. Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: a controlled and randomized clinical trial. Phytomedicine 11, 375–382. Hnatyszyn, O., Mino, J., Gorzalczany, S., Opezzo, J., Ferraro, G., Coussio, J., Acevedo, C., 1999. Diuretic activity of an aqueous extract of Phyllanthus sellowianus. Phytomedicine 6, 177–179. Hook, I., McGee, A., Henman, M., 1993. Evaluation of dandelion for diuretic activity and variation in potassium content. International Journal of Pharmacognosy 31, 29–34. Johnson, P.B., Abdurahman, E.M., Tiam, E.A., Abdu-Aguye, I., Hussaini, I.M., 1999. Euphorbia hirta leaf extracts increase urine output and electrolytes in rats. Journal of Ethnopharmacology 65, 63–69. Jones, K., 2007. Pau d’arco: Immune Power from the Rain Forest. Healing Arts Press, Toronto, Canada. Jouad, H., Haloui, M., Rhiouani, H., El Hilaly, J., Eddouks, M., 2001a. Ethnobotanical survey of medicinal plants used for the treatment of diabetes, cardiac and renal diseases in the North centre region of Morocco (Fez-Boulemane). Journal of Ethnopharmacology 77, 175–182. Jouad, H., Lacaille-Dubois, M.A., Eddouks, M., 2001b. Chronic diuretic effect of the water extract of Spergularia purpurea in normal rats. Journal of Ethnopharmacology 75, 219–223. Jouad, H., Lacaille-Dubois, M.A., Lyoussi, B., Eddouks, M., 2001c. Effects of the flavonoids extracted from Spergularia purpurea Pers. on arterial blood pressure and renal function in normal and hypertensive rats. Journal of Ethnopharmacology 76, 159–163. Kim, D., Yokozawa, T., Hattori, M., Kadota, S., Namba, T., 2000. Effects of aqueous extracts of Apocynum venetum leaves on spontaneously hypertensive, renal hypertensive and NaCl-fed-hypertensive rats. Journal of Ethnopharmacology 72, 53–59. King, S.E., Grace, J.B., 2000. The effects of gap size and disturbance type on invasion of wet pine savanna by cogongrass, Imperata cylindrica (Poaceae). American Journal of Botany 87, 1279–1286. Koch, E., 2001. Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms. Planta Medica 67, 489–500. Kreydiyyeh, S.I., Usta, J., 2002. Diuretic effect and mechanism of action of parsley. Journal of Ethnopharmacology 79, 353–357. Lahlou, S., Tahraoui, A., Israili, Z., Lyoussi, B., 2006. Diuretic activity of the aqueous extracts of Carum carvi and Tanacetum vulgare in normal rats. Journal of Ethnopharmacology 110 (3), 458–463. Laranja, S.M., Bergamaschi, C.M., Schor, N., 1991. Evaluation of acute administration of natural products with potential diuretic effects, in humans. Mem´orias do Instituto Oswaldo Cruz 86 (suppl. 2), 237– 240. Lemus, I., Garcia, R., Erazo, S., Pena, R., Parada, M., Fuenzalida, M., 1996. Diuretic activity of an Equisetum bogotense tea (Platero herb): evaluation in healthy volunteers. Journal of Ethnopharmacology 54, 55–58. Leuschner, J., 1995. Anti-inflammatory, spasmolytic and diuretic effects of a commercially available Solidago gigantea Herb. extract. Arzneimittelforschung 45, 165–168. Lu, G.W., Miura, K., Yukimura, T., Yamamoto, K., 1994. Effects of extract from Clerodendron trichotomum on blood pressure and renal function in rats and dogs. Journal of Ethnopharmacology 42, 77–82. Maghrani, M., Zeggwagh, N.A., Haloui, M., Eddouks, M., 2005a. Acute diuretic effect of aqueous extract of Retama raetam in normal rats. Journal of Ethnopharmacology 99, 31–35. Maghrani, M., Zeggwagh, N.A., Lemhadri, A., El Amraoui, M., Michel, J.B., Eddouks, M., 2004. Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus. Journal of Ethnopharmacology 91, 309–316.

30

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31

Maghrani, M., Zeggwagh, N.A., Michel, J.B., Eddouks, M., 2005b. Antihypertensive effect of Lepidium sativum L. in spontaneously hypertensive rats. Journal of Ethnopharmacology 100, 193–197. Maksimovic, Z., Dobric, S., Kovacevic, N., Milovanovic, Z., 2004. Diuretic activity of Maydis stigma extract in rats. Pharmazie 59, 967–971. Martin, K.W., Ernst, E., 2003. Antiviral agents from plants and herbs: a systematic review. Antiviral Therapy 8, 77–90. Martinez, C.S., Carricajo, F.C., Perez-Fernandez, R., 2004. Effect of an integral suspension of Lepidium latifolium on prostate hyperplasia in rats. Fitoterapia 75, 187–191. Materson, B.J., 1983. Insights into intrarenal sites and mechanisms of action of diuretic agents. Americal Heart Journal 106, 188–208. Matsubara, T., Bohgaki, T., Watarai, M., Suzuki, H., Ohashi, K., Shibuya, H., 1999. Antihypertensive actions of methylripariochromene A from Orthosiphon aristatus, an Indonesian traditional medicinal plant. Biological and Pharmaceutical Bulletin 22, 1083–1088. Mekhfi, H., El Haouari, M., Legssyer, A., Bnouham, M., Aziz, M., Atmani, F., Remmal, A., Ziyyat, A., 2004. Platelet anti-aggregant property of some Moroccan medicinal plants. Journal of Ethnopharmacology 94, 317– 322. Melis, M.S., 1992a. Influence of calcium on the blood pressure and renal effects of stevioside. Brazilian Journal of Medical and Biological Research 25, 943–949. Melis, M.S., 1992b. Renal excretion of stevioside in rats. Journal of Natural Products 55, 688–690. Melis, M.S., 1992c. Stevioside effect on renal function of normal and hypertensive rats. Journal of Ethnopharmacology 36, 213–217. Melis, M.S., 1995. Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects. Journal of Ethnopharmacology 47, 129–134. Melis, M.S., 1996. A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats. Brazilian Journal of Medical and Biological Research 29, 669–675. Melis, M.S., 1999. Effect of crude extract of Stevia rebaudiana on renal water and electrolytes excretion. Phytomedicine 6, 247–250. Melis, M.S., Sainati, A.R., 1991a. Effect of calcium and verapamil on renal function of rats during treatment with stevioside. Journal of Ethnopharmacology 33, 257–262. Melis, M.S., Sainati, A.R., 1991b. Participation of prostaglandins in the effect of stevioside on rat renal function and arterial pressure. Brazilian Journal of Medical and Biological Research 24, 1269–1276. Musabayane, C.T., Munjeri, O., Mdege, N.D., 2003. Effects of Helichrysum ceres extracts on renal function and blood pressure in the rat. Renal Failure 25, 5–14. Naik, V.R., Agshikar, N.V., Abraham, G.J., 1980. Analgesic and antiinflammatory activity in alcoholic extracts of Cucumis trigonus Roxburghii. A preliminary communication. Pharmacology 20, 52–56. Naik, V.R., Agshikar, N.V., Abraham, G.J., 1981. Cucumis trigonus Roxb. II. Diuretic activity. Journal of Ethnopharmacology 3, 15–19. Navarro, E., Alonso, J., Rodriguez, R., Trujillo, J., Boada, J., 1994. Diuretic action of an aqueous extract of Lepidium latifolium L. Journal of Ethnopharmacology 41, 65–69. Navarro, E., Alonso, P.J., Alonso, S.J., Trujillo, J., Perez, C., Toro, M.V., Ayuso, M.J., 2000. Cardiovascular activity of a methanolic extract of Digitalis purpurea spp. heywoodii. Journal of Ethnopharmacology 71, 437–442. Nedi, T., Mekonnen, N., Urga, K., 2004. Diuretic effect of the crude extracts of Carissa edulis in rats. Journal of Ethnopharmacology 95, 57–61. Neuhauser, B., Beine, S., Verwied, S.C., Luhrmann, P.M., 1997. Coffee consumption and total body water homeostasis as measured by fluid balance and bioelectrical impedance analysis. Annals of Nutrition and Metabolism 41, 29–36. Odigie, I.P., Ettarh, R.R., Adigun, S.A., 2003. Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats. Journal of Ethnopharmacology 86, 181–185. Olah, N.K., Radu, L., Mogosan, C., Hanganu, D., Gocan, S., 2003. Phytochemical and pharmacological studies on Orthosiphon stamineus Benth. (Lamiaceae) hydroalcoholic extracts. Journal of Pharmaceutical and Biomedical Analysis 33, 117–123.

Onyenekwe, P.C., Ajani, E.O., Ameh, D.A., Gamaniel, K.S., 1999. Antihypertensive effect of roselle (Hibiscus sabdariffa) calyx infusion in spontaneously hypertensive rats and a comparison of its toxicity with that in Wistar rats. Cell Biochemistry and Function 17, 199–206. Ozsoy-Sacan, O., Yanardag, R., Orak, H., Ozgey, Y., Yarat, A., Tunali, T., 2006. Effects of parsley (Petroselinum crispum) extract versus glibornuride on the liver of streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 104, 175–181. Pantoja, C.V., Chiang, L.C., Norris, B.C., Concha, J.B., 1991. Diuretic, natriuretic and hypotensive effects produced by Allium sativum (garlic) in anaesthetized dogs. Journal of Ethnopharmacology 31, 325– 331. Pantoja, C.V., Martin, N.T., Norris, B.C., Contreras, C.M., 2000. Purification and bioassays of a diuretic and natriuretic fraction from garlic (Allium sativum). Journal of Ethnopharmacology 70, 35–40. Pantoja, C.V., Norris, B.C., Contreras, C.M., 1996. Diuretic and natriuretic effects of chromatographically purified fraction of garlic (Allium sativum). Journal of Ethnopharmacology 52, 101–105. Passmore, A.P., Kondowe, G.B., Johnston, G.D., 1987. Renal and cardiovascular effects of caffeine: a dose-response study. Clinical Science 72, 749– 756. Perez Gutierrez, R.M., Laguna, G.Y., Walkowski, A., 1985. Diuretic activity of Mexican Equisetum. Journal of Ethnopharmacology 14, 269–272. Poli, A., Nicolau, M., Simoes, C.M., Nicolau, R.M., Zanin, M., 1992. Preliminary pharmacologic evaluation of crude whole plant extracts of Elephantopus scaber. Part I: In vivo studies. Journal of Ethnopharmacology 37, 71–76. Puschett, J.B., 1994. Pharmacological classification and renal actions of diuretics. Cardiology 84 (suppl. 2), 4–13. Rabbia, F., Martini, G., Cat, G.G., Milan, A., Chiandussi, L., Veglio, F., 2001. Antihypertensive drugs and sympathetic nervous system. Clinical and Experimental Hypertension 23, 101–111. Racz-Kotilla, E., Racz, G., Solomon, A., 1974. The action of Taraxacum officinale extracts on the body weight and diuresis of laboratory animals. Planta Medica 26, 212–217. Rahman, K., Lowe, G.M., 2006. Garlic and cardiovascular disease: a critical review. The Journal of Nutrition 136, 736S–740S. Ratnasooriya, W.D., Pieris, K.P., Samaratunga, U., Jayakody, J.R., 2004. Diuretic activity of Spilanthes acmella flowers in rats. Journal of Ethnopharmacology 91, 317–320. Reyes, A.J., Taylor, S.H., 1999. Diuretics in cardiovascular therapy: the new clinicopharmacological bases that matter. Cardiovascular Drugs and Therapy 13, 371–398. Rhiouani, H., Settaf, A., Lyoussi, B., Cherrah, Y., Lacaille-Dubois, M.A., Hassar, M., 1999. Effects of saponins from Herniaria glabra on blood pressure and renal function in spontaneously hypertensive rats. Therapie 54, 735– 739. Ribeiro, R.A., de Barros, F., de Melo, M.M., Muniz, C., Chieia, S., Wanderley, M.D., Gomes, C., Trolin, G., 1988. Acute diuretic effects in conscious rats produced by some medicinal plants used in the state of Sao Paulo, Brasil. Journal of Ethnopharmacology 24, 19–29. Rocha, M.J., Fulgencio, S.F., Rabetti, A.C., Nicolau, M., Poli, A., Simoes, C.M., Ribeiro-do-Valle, R.M., 1994. Effects of hydroalcoholic extracts of Portulaca pilosa and Achyrocline satureioides on urinary sodium and potassium excretion. Journal of Ethnopharmacology 43, 179–183. Schutz, K., Carle, R., Schieber, A., 2006. Taraxacum—a review on its phytochemical and pharmacological profile. Journal of Ethnopharmacology 107, 313–323. Selvam, R., Kalaiselvi, P., Govindaraj, A., Bala, M.V., Sathish Kumar, A.S., 2001. Effect of Aerva lanata leaf extract and Vediuppu chunnam on the urinary risk factors of calcium oxalate urolithiasis during experimental hyperoxaluria. Pharmacological Research 43, 89–93. Sharafatullah, T., Khan, M.I., Ahmad, S.I., 1986. Diuretic action of garlic extract in anaesthetised normotensive dogs. The Journal of the Pakistan Medical Association 36, 280–282. Sharifi, A.M., Darabi, R., Akbarloo, N., 2003. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity. Life Sciences 73, 2963–2971.

C.I. Wright et al. / Journal of Ethnopharmacology 114 (2007) 1–31 Shirwaikar, A., Issac, D., Malini, S., 2004. Effect of Aerva lanata on cisplatin and gentamicin models of acute renal failure. Journal of Ethnopharmacology 90, 81–86. Singh, I., Mok, M., Christensen, A.M., Turner, A.H., Hawley, J.A., 2007. The effects of polyphenols in olive leaves on platelet function. Nutrition, Metabolism and Cardiovascular diseases. Singh, R.C., Sisodia, C.S., 1970. Pharmacodynamic investigations into the diuretic activity of Cucumis melo seed (ether extract). Indian Journal of Medical Research 58, 505–512. Singh, R.C., Sisodia, C.S., 1971. Effect of Tribulus terrestris fruit extracts on chloride and creatinine renal clearances in dogs. Indian Journal of Physiology and Pharmacology 15, 93–96. Somova, L.I., Shode, F.O., Moodley, K., Govender, Y., 2001. Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica and Alepidea amatymbica. Journal of Ethnopharmacology 77, 165–174. Somova, L.I., Shode, F.O., Ramnanan, P., Nadar, A., 2003. Antihypertensive, antiatherosclerotic and antioxidant activity of triterpenoids isolated from Olea europaea, subspecies africana leaves. Journal of Ethnopharmacology 84, 299–305. Sripanidkulchai, B., Wongpanich, V., Laupattarakasem, P., Suwansaksri, J., Jirakulsomchok, D., 2001. Diuretic effects of selected Thai indigenous medicinal plants in rats. Journal of Ethnopharmacology 75, 185–190. Sriplang, K., Adisakwattana, S., Rungsipipat, A., Yibchok-Anun, S., 2007. Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 109, 510–514. Srividya, N., Periwal, S., 1995. Diuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus. Indian Journal of Experimental Biology 33, 861–864. Tahraoui, A., El Hilaly, J., Israili, Z.H., Lyoussi, B., 2007. Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province). Journal of Ethnopharmacology 110, 105–117. Tahri, A., Yamani, S., Legssyer, A., Aziz, M., Mekhfi, H., Bnouham, M., Ziyyat, A., 2000. Acute diuretic, natriuretic and hypotensive effects of a continuous perfusion of aqueous extract of Urtica dioica in the rat. Journal of Ethnopharmacology 73, 95–100. Taufiq-Ur-Rahman, M., Shilpi, J.A., Ahmed, M., Faiz, H.C., 2005. Preliminary pharmacological studies on Piper chaba stem bark. Journal of Ethnopharmacology 99, 203–209. Thole, J.M., Kraft, T.F., Sueiro, L.A., Kang, Y.H., Gills, J.J., Cuendet, M., Pezzuto, J.M., Seigler, D.S., Lila, M.A., 2006. A comparative evaluation of the anticancer properties of European and American elderberry fruits. Journal of Medicinal Food 9, 498–504.

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Twaij, H.A., Kery, A., Al Khazraji, N.K., 1983. Some pharmacological, toxicological and phytochemical investigations on Centaurea phyllocephala. Journal of Ethnopharmacology 9, 299–314. Udupihille, M., Jiffry, M.T., 1986. Diuretic effect of Aerva lanata with water, normal saline and coriander as controls. Indian Journal of Physiology and Pharmacology 30, 91–97. Unander, D.W., Venkateswaran, P.S., Millman, I., Bryan, H.H., Blumberg, B.S., 1990. Phyllanthus species: sources of new antiviral compounds. In: Janick, J., Simon, J.E. (Eds.), Advances in New Crops. Timber Press, Portland, USA, pp. 518–521. Uzun, E., Sariyar, G., Adsersen, A., Karakoc, B., Otuk, G., Oktayoglu, E., Pirildar, S., 2004. Traditional medicine in Sakarya province (Turkey) and antimicrobial activities of selected species. Journal of Ethnopharmacology 95, 287–296. Vargas, R., Perez, R.M., Perez, S., Zavala, M.A., Perez, C., 1999. Antiurolithiatic activity of Raphanus sativus aqueous extract on rats. Journal of Ethnopharmacology 68, 335–338. Vargas, S.R., Perez Gutierrez, R.M., 2002. Diuretic and urolithiatic activities of the aqueous extract of the fruit of Randia echinocarpa on rats. Journal of Ethnopharmacology 83, 145–147. Velazquez, D.V., Xavier, H.S., Batista, J.E., Castro-Chaves, C., 2005. Zea mays L. extracts modify glomerular function and potassium urinary excretion in conscious rats. Phytomedicine 12, 363–369. Vered, Y., Grosskopf, I., Palevitch, D., Harsat, A., Charach, G., Weintraub, M.S., Graff, E., 1997. The influence of Vicia faba (broad bean) seedlings on urinary sodium excretion. Planta Medica 63, 237–240. Vetrichelvan, T., Jegadeesan, M., 2002. Anti-diabetic activity of alcoholic extract of Aerva lanata (L.) Juss. ex Schultes in rats. Journal of Ethnopharmacology 80, 103–107. Vouldoukis, I., Lacan, D., Kamate, C., Coste, P., Calenda, A., Mazier, D., Conti, M., Dugas, B., 2004. Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity. Journal of Ethnopharmacology 94, 67–75. Williams, B., Poulter, N.R., Brown, M.J., Davis, M., McInnes, G.T., Potter, J.F., Sever, P.S., Thom, S.M., 2004. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. British Medical Journal 328, 634–640. Wright, C.I., Kroner, C.I., Draijer, R., 2005. Raynaud’s phenomenon and the possible use of foods. Journal of Food Science 70, R67–R75. Xu, G., Liang, Q., Gong, Z., Yu, W., He, S., Xi, L., 2006. Antitumor activities of the four sesquiterpene lactones from Elephantopus scaber L. Experimental Oncology 28, 106–109. Yarnell, E., 2002. Botanical medicines for the urinary tract. World Journal of Urology 20, 285–293.