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Medicinal plants used for neurological and mental disorders in Navarra and their validation from official sources
Journal of Ethnopharmacology 169 (2015) 263–268
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Medicinal plants used for neurological and mental disorders in Navarra and their validation from official sources María Isabel Calvo a,n, Rita Yolanda Cavero b a b
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain Department of Environmental Biology, Faculty of Sciences, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain
art ic l e i nf o
a b s t r a c t
Article history: Received 3 February 2015 Received in revised form 17 April 2015 Accepted 18 April 2015 Available online 25 April 2015
Ethnopharmacological relevance: This paper provides important ethnopharmacological information on plants used in neurological and mental disorders in Navarra. Material and methods: Information was collected using semi-structured ethnobotanical interviews with 667 informants in 265 locations. In order to confirm the pharmacological validation of the uses claimed by the informants, monographs from Official International Agencies (ESCOP, Commission E, WHO and EMA) were reviewed. A literature review was conducted focusing on the plants that were widely used but had no published monograph. Results: A total of 172 pharmaceutical uses were reported, for 46 plants and 26 families, mainly represented by Lamiaceae (15%), Asteraceae (13%), Rosaceae and Rutaceae (7%, each one), and Clusiaceae, Malvaceae, Papaveraceae and Urticaceae (4%, each one). The most frequently used parts were inflorescence (39%), flowered aerial parts (16%), and aerial parts (13%), followed by inflorescence bract (8%) and leaves (7%). Nine out of 46 plants (20%) and 81 of 172 uses (47%), have already been pharmacologically validated. The remaining 37 plants (of total 46, 80%) have been reported for neurological and mental disorders and need to be screened through standard pharmacological and clinical procedures for their activities. The most used species are Chamaemelum nobile (L.) All., Jasonia glutinosa (L.) DC., and Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman, in all cases the administration as infusion. Conclusions: Data indicate a high degree of plants knowledge in Navarra regarding neurological and mental disorders. The present study constitutes a good basis for further phytochemical and pharmacological research of C. nobile, J. glutinosa and S. chamaecyparissus, which could be of interest in the design of new inexpensive, effective and safe drugs. & 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Nervous system Ethnopharmacology Chamaemelum nobile Jasonia glutinos Santolina chamaecyparissus Spain
1. Introduction Traditional medicine is used worldwide and it is of great economic importance in the 21st century (Bussmann, 2013). Among the positive aspects of traditional medicine, researchers have mentioned diversity, flexibility, accessibility, relevance in developing countries, increasing popularity in developed countries, relative low cost, few side effects of medicinal plants (Payyappallimana, 2010). The World Health Organization (WHO) estimates that over one billion people worldwide suffer from illnesses of the central nervous system. Besides injuries of the brain and the spinal cord, these include a large number of neurological or mental illnesses. Neurological disorders are diseases of the central and peripheral nervous system. These disorders include epilepsy, Alzheimer disease and other dementias, migraine and other headache disorders, n
Corresponding author. Tel.: þ 34 948425600x806239; fax: þ 34 948425740. E-mail address: [email protected] (M.I. Calvo).
http://dx.doi.org/10.1016/j.jep.2015.04.035 0378-8741/& 2015 Elsevier Ireland Ltd. All rights reserved.
multiple sclerosis, Parkinson's disease, neuroinfections, brain tumors and traumatic disorders of the nervous system. Mental disorders, on the other hand, are psychiatric illnesses or diseases, (i.e. anxiety, depressive and schizophrenia), which appear primarily as abnormalities of thought, feeling or behavior, producing either distress or impairment of function. These illnesses not only cause great human suffering, but are also linked with enormous costs – stays in hospital, loss of working hours, early retirement and, in many cases, life-long care. These social, ethical and economic reasons call for the urgent improvement of medical research in this field (WHO, 2001). The investigation carried out by our research group in Navarra began in 2003 and continues to the present. The high number of plants collected to date has allowed the publication of several manuscripts for various affections: digestive (Calvo et al., 2013), dermatological (Cavero et al., 2013), cardiovascular (Calvo and Cavero, 2014), respiratory (Cavero and Calvo, 2014) and musculoskeletal diseases (Cavero and Calvo, 2015). Following on from this, the aims of the present paper are: i) to collect information
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M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 169 (2015) 263–268
about plant species used for problems associated with the nervous system; ii) to analyze these ethnopharmacological data; iii) to look for coincidences of the reported uses in the literature in order to validate them from a pharmacological viewpoint; and, iv) to propose highly plants reported without bibliographic validation.
2. Material and methods 2.1. Study area Navarra is a territory of 10,421 km2 placed to the North of the Iberian Peninsula, where three zones can be differed: the Mountain on the North, the Riverside on the South, and both separated by a zone of transition, the Middle Navarra. There are two macrobioclimates, Temperate and Mediterranean. These factors provide a great diversity of plant communities and a rich flora (2,650 vascular plants) (Cavero et al., 2013).
study, medicinal plants used for neurological and mental disorders were analyzed. To confirm the reported uses by participants in the study, the literature was reviewed in order to carry out a pharmacological validation in reported plants, using monographs (sometimes linked to databases) from official sources: the European Scientific Cooperative on Phytotherapy (ESCOP, 2003–2009), German Commission E (Blumenthal et al., 2000), World Health Organization (WHO, 1999–2010), European Medicines Agency (www.ema. europa.eu/ema/index), European Pharmacopoeia (2013) and Real Farmacopea Española (Real Farmacopea Española, 2015) monographs. These monographs are responsible for evaluating the quality, safety and efficacy of herbs. A literature review was carried out for the plants that were reported to be in widespread use, for which no monograph exists.
2.2. Methodology
3. Results and discussion
Information was collected using semi-structured ethnobotanical interviews as a technique for data collection from informants. Interviews were practiced from 2003 to 2014. Native people, 667 informants (mean age470 years) of 265 locations, were interviewed in Basque and Castilian language, both official languages of Navarra. In the field work we noted for each species the local name, place and collection method, drying and preservation system, parts or organs used and method of preparation, dosage and administration. Voucher samples are kept in the PAMP Herbarium at the Faculty of Science (University of Navarra). In the present
3.1. Botanical information A total of 172 pharmaceutical uses were reported, belonging to 46 plants (78% native and 22% introduced species from other continents, or other European regions). The complete catalog of the ethnoflora of the surveyed territory is given in Akerreta (2009). The 46 medicinal plants belong to 26 families, mainly represented by Lamiaceae (15%), Asteraceae (13%), Rosaceae and Rutaceae (7%, each one), and Clusiaceae, Malvaceae, Papaveraceae and Urticaceae (4%, each one).
Table 1 Plants with validation from official sources. Plant (Family, voucher specimen)
Popular name
Crataegus monogyna Jacq. (Rosaceae, 18723) Humulus lupulus L. (Cannabaceae, 21144)
Ph Administration Preparation
Popular use (number of use FU Monograph reports)
Ellori zuria, espino, Flower espino blanco
A, B
Internal (I)
Infusion
Lupibelarra, lúpulo
Female inflorescence
A
External (D)
To put inside the pillow.
Anxiety, for nerves, tranquilizer and relaxing (5), for sadness (1) To sleep better (3)
San Juan belarra, hipérico, hierba de San Juan Lavandula angustifolia Mill Espliego, lavanda ssp.angustifolia (Lamiaceae, 21575) Melissa officinalis L. Melisa (Lamiaceae, 18688) Rosmarinus officinalis L. Romero (Lamiaceae, 21655)
Flowered aerial part, flower Flowed aerial part
A, B
Internal (D) Internal (D)
Infusion Infusion
A, B
Internal (D)
Leaf, aerial part Flower Aerial part, flowered aerial part
A, B A, B
Sambucus nigra L. ssp. Astunpa, intsusa, nigra (Adoxaceae, 18661) sabuko, saúco
Internal bark, leaf
A, B
Inflorescence Inflorescence
Hypericum perforatum L. (Clusiaceae, 21559)
Tilia cordata Mill. Tilo (Tiliaceae, 22028) Tilia platyphyllos Scop. ssp. Tilo platyphyllos (Tiliaceae, 18752)
Part used
Inflorescence bract, inflorescence
6 1,3,4
3 2,4
To lift the spirits, depression (6)
6 1,2,3,4
Infusion
Tranquilizer (2)
2 1,2,3,4
Internal (I)
Infusion
6 1,4
External (I)
5 3
Internal (I) External (I)
To rub with the macerated in wine or alcohol, or with wine decoction, vapors. Infusion or maceration in wine Ointment with lard and wax, roasted in poultice Poultice or ointment with lard and wax.
Tranquilizer and relaxing (5), depression (1) Analgesic (3)
Stimulant (2) Analgesic (2)
3 4 3a
A
Internal (I) Internal (D)
Smoke inhalation Infusion
Analgesic (2) For nerves and to relax (4)
3 4 4
A
Internal (D)
Infusion
For nerves, tranquilizer and 45 4 relaxing, to sleep better (45)
Ph: Pharmacopeia; A: European Pharmacopoeia; B: Real Farmacopea Española; F: fresh; D: dry; I: without distinction; 1: ESCOP monograph; 2: German Commission E monograph; 3. WHO monograph; 4: EMA monograph. a
Different part used; FU: frequency of uses.
M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 169 (2015) 263–268
The most frequently used parts were inflorescence (39%), flowered aerial parts (16%), aerial parts (13%), inflorescence bract (8%), leaves (7%), flowers (5%), fruits (3%) and petals (2%). Plants were used dry (61%), fresh (19%), or either (18%) and lost knowledge (2%) for administration in different forms. The percentage of internal uses was five times higher than that for external uses (84% and 16%, respectively), and the most important forms of preparation were infusion (86%), decoction (9%), and in lower proportions, maceration (3%), and vapors (2%); for external uses, the most important form were poultices (43%), maceration (29%), and ointment (11%) 3.2. Pharmacopoeias references Nine out of 46 plants (20%) and 81 of 172 total uses (47%), have already been pharmacologically validated for neurological and mental diseases by ESCOP, Commission E, WHO and EMA Monographs (Table 1). It is important to highlight that Hypericum perforatum L., and Lavandula angustifolia Mill ssp.angustifolia (two of nine plants, 22%) have monographs in the four agencies taken into consideration. All of plants cited in Table 1 have monograph in the European Pharmacopoeia and/or Real Farmacopea Española. 3.3. Futher pharmacological data The remaining 37 of 46 plants (80%) and 91 of 172 uses (53%) were reported for nervous system troubles and need to be screened through standard scientific procedures for their actions (Table 2). We found that the most widely treated affections fell into six pathological categories: analgesic (14%), antidepressant (5%), to clear the mind (7%), headache (41%), insomnia (10%) and nervousness (23%). In this study, the results showed 9 plants as analgesic (agents that alleviate pain without causing anesthesia), being the most cited Malva sylvestris L. (3 uses of 91 total uses, 3%) and Urtica dioica L. (2 uses, 2%). The infusion of flowered aerial part from Hypericum androsaemum L. was cited as antidepressant for sadness (emotional pain associated with, or characterized by feelings of disadvantage, loss, despair, helplessness and sorrow) or “to lift up the spirit” (2 uses, 2%). With the same therapeutic indication, the maceration in anisette from Prunus spinosa L. was also recopilated (2 uses, 2%). The most reported application to clear the mind (4 uses, 4%) was the infusion of flowered aerial part from Jasonia glutinosa (L.) DC. Headache or cephalagia is a pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The most widely cited plants for this affection were J. glutinosa (12 uses of 91 total uses, 13%), Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (11 uses, 12%), Chamaemelum nobile (L.) All. (5 uses, 5%) and Verbena officinalis L. (2 uses, 2%). The first three plants were administered internally in infusion and the last one, V. officinalis, a poultice using white egg as excipient. Eight plants were reported to sleep aid or insomnia. The inflorescence of Lavandula latifolia Medicus was the most important plant (2 uses, 2%) in two different form of administration, infusion or introduced into the pillow overnight to smell it. It is important to highlight the importance of infusions from C. nobile (4 uses, 4%), S. chamaecyparissus (3 uses, 3%) and U. dioica (2 uses, 2%) as tranquilizers for nervousness. In summary, the most widely cited plants for nervous system problems belong to the Asteraceae family: C. nobile (10 uses, 11%), J. glutinosa (16 uses, 18%) and S. chamaecyparissus ssp. squarrosa (14 uses, 15%).
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C. nobile, commonly known as ‘manzanilla’ or ‘kamamila’, is a perennial herb. It is native to Southwest Europe (France, Spain and Portugal) but the plant is present all over Europe, North Africa and Southwest Asia. The plant is cultivated mainly in England, Belgium, France, Germany, Hungary, Poland, Bulgaria, Egypt and Argentina. Although ‘manzanilla’ flowerheads are described as antiseptic, antibiotic, disinfectant, bactericidal, fungicidal and vermifuge. It has been used for centuries as anti-inflammatory, antioxidant, mild astringent, mild sedative, antispasmodic, antibacterial and healing medicine (Guimarães et al., 2013), the European Medicines Agency (EMA-HMPC, 2011) has only approved the traditional use of oral dosage forms (decoctions and infusions) for the symptomatic treatment of mild gastrointestinal spasmodic affections such as bloating and flatulence, and for the inflammation of the oropharyngeal cavity. The uses of ‘manzanilla’ that are described in the Commission E monograph (Blumenthal et al., 1998) are similar. Regarding neurological and mental affections, a review of literature from etnopharmacological studies has showed that C. nobile is used in different regions of Spain: Basque Country, Cantabria, Navarra and Principality of Asturias (Akerreta, 2009, and references cited therein; Cavero et al., 2011a; MenendezBaceta et al., 2014). Additionally, one ethnopharmacological references was found in Portuguese Republic (Camejo-Rodrigues, 2001). Different classes of bioactive constituents are present in ‘manzanilla’, including volatile oil and sesquiterpenes (Farhoudi, 2013), hydroperoxides (Rucker et al., 1989), flavonoids, catechins, phenolic acids and coumarins (Tschan et al., 1996), polyacetylenes (Ma et al., 2007), triterpenes and steroids (Fauconnier et al., 1996). This chemical composition may be responsible for spasmolytic, anxiolitic and vascular effect of ethanolic and aqueous extract (Dooraghi et al., 2010; Zeggwagh et al., 2013), which could explain its applications in nervous system problems, like as nervousness and headaches (Carnat et al., 2004). Jasonia glutinosa is very popular as a stomachic as well as a component in preparations showing beneficial effects such as antispasmodic and anti-inflammatory drug in relation to nervous system problems Iberian Peninsula, Spain: Andalusia, Aragon, Cantabria, Catalonia, Navarra and Valencian Community (Akerreta, 2009 and references cited therein; Calvo et al., 2011; Cavero et al., 2011a, 2011b). Nonsteroidal anti-inflammatory drugs (NSAIDs), along with analgesics, are considered a first-line treatment for sufferers of mild to moderate headache pain. NSAIDs, such as ibuprofen and naproxen, relieve pain by inhibiting prostaglandins, compounds implicated in the inflammatory responses. These drugs help reduce the swelling associated with the pain of headaches. In various phytochemical studies performed on J. glutinosa it was found to contain essential oils (Guillen and Ibargoitia, 1996; Romero et al., 2003), flavonoids (Rubio et al., 1995) and sesquiterpenoids (Bermejo et al., 2002; Sanchez-Martinez et al., 2000). Sesquiterpenes and flavonoids are secondary metabolites widely distributed in the higher plant kingdom and are known to show diverse biological and pharmacological actions. For this reason, these compounds have been evaluated for their in vitro antiinflammatory activity in cellular systems generating cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) metabolites. Both types of compounds showed a significant effect on thromboxane B2 (TXB2)-release induced by calcium ionophore in human platelets, although with less potency than the reference drug ibuprofen (Villaescusa et al., 1996). In addition, the sesquiterpenes, such as lucinone, glutinone, epi-kutdtriol and kutdtriol, showed antiinflammatory properties in a previous work with peritoneal mice macrophages (Bermejo et al., 2002). All sesquiterpenes exerted
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Table 2 Plant without validation from official sources. Affection
Plant (Family, voucher specimen)
Popular name
Part used
Administration Preparation (number of use reports)
Analgesic
Allium sativum L. (Liliaceae, 21718)
Ajo
Bulb
Internal (F)
Citrus limon (L.) Burm. (Rutaceae, 21189)
Limón
Fruit
External (F)
Juglans regia L. (Juglandaceae, 18683)
Noguera, nogal
External (F)
Laurus nobilis L. (Lauraceae, 21715) Malva sylvestris L. (Malvaceae, 18748)
Laurel Malva
Plantago lanceolata L. (Plantaginaceae, 18716) Triticum aestivum L. (Poaceae, 18797) Urtica dioica L. (Urticaceae, 19652)
External bark, leaf Leaf Aerial part, flower Leaf
Plantinabelarra, cincovenas, llantén Trigo Fruit (Seed) Auxina, oxina, ortiga Aerial part
Vitis vinifera L. (Vitaceae, 21809)
Ardoaegosite, uva, vid Milazulo haundi, hipérico Elorri beltza, patxaran, arañones Berbenabelarra, kolpebelarra, verbena Armuelle
Antidepressant Hypericum androsaemum L. (Clusiaceae, 21551) Prunus spinosa L. (Rosaceae, 21969) Verbena officinalis L. (Verbenaceae, 21770) Clear the mind Atriplex patula L. (Amaranthaceae, 21168) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Jasonia glutinosa (L.) DC. (Asteraceae, 21252) Headache Bidens aurea (Aiton) Sherff (Asteraceae, 19675) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Jasonia glutinosa (L.) DC. (Asteraceae, 21252) Jasonia tuberosa (L.) DC. (Asteraceae, 18772) Parietaria judaica L. (Urticaceae, 21723) Petroselinum crispum (Mill.) Fuss (Apiaceae, 22061) Polygonum lapathifolium L. (Polygonaceae, 21908) Rosa sp. (Rosaceae, 18726) Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (Asteraceae, 18775) Thymus vulgaris L. (Lamiaceae, 21713) Verbena officinalis L. (Verbenaceae, 21770) Insomnia
Nervousness
Centranthus ruber (L.) DC. ssp. ruber (Caprifoliaceae, 21765) Citrus sinensis (L.) Osbeck (Rutaceae, 22514) Lavandula latifolia Medicus (Lamiacaea, 21579) Nerium oleander L. ssp. oleander (Apocynaceae, 18785) Papaver rhoeas L. (Papaveraceae, 21881) Pinus sylvestris L. (Pinaceae, 18798) Rosa sp. (Rosaceae, 18726) Ruta montana (L.) L. (Rutaceae, 21997) Alcea rosea L. (Malvaceae, 21821) Calamintha nepeta (L.) Savi ssp. nepeta (Lamiaceae, 21572) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Centranthus ruber (L.) DC. ssp. ruber (Caprifoliaceae, 21765)
2
1
1
Boiled in poultice with olive oil (1) Boiled in poultice or ointment with lard and wax (3) Boiled in poultice (1)
1 3
External (I) Internal (F), external (I) Internal (F)
Poultice with egg or olive oil (1) Infusion for 3 days (1), to rub (1)
1 2
Burn wine and take (1)
1 13
Flowered aerial part Fruit
Internal (F, I)
Infusion (2)
2
Internal (F)
Maceration in anisette (2)
2
Flowered aerial part
Internal (I)
Infusion (1)
1
Leaf
Internal (F)
Infusion or comestible (1)
1
Inflorescence
Internal (D)
Infusión (1)
1
Flowered aerial part Aerial part
Internal (D)
Infusion (4)
4
Internal (F)
Infusión (1)
1
Inflorescence
Internal (D)
Infusion (5)
5
Internal (D)
Infusion (12)
12
Internal (D)
Decoction (1)
1
Paretabelarra, parietaria, rompepiedras Perejil
Flowered aerial part Flowered aerial part Aerial part
Internal (F)
Decoction and take a gulp for 20 days (1)
1
Leaf
External (F)
1
Pimienta acuática
Aerial part
Internal (I)
Poultice with decoction for three days, three times daily (1) Infusion for 3 times/day (1)
Rosa Manzanilla, manzanilla del monte Tomillo
Fruit, petal Inflorescence
Internal (D) Internal (D)
Decoction (1) Infusion (11)
Flowered aerial part Aerial part
External (I)
Soak the head with the decoction (1)
1
Berbenabelarra, kolpebelarra, verbena Milamores, valeriana Inflorescence
External (F)
Poultice with white of eggs (2)
2 37
Internal (Lk)
Infusion (1)
1
Naranjo
Fruit
Internal (F)
Decoction and taken before bedtime (1)
1
Espliego, lavanda
Inflorescence
Infusion (1), to put inside the pillow (1)
2
Adelfa
Leaf
Internal (I), external (D) External (F)
Rub the head with two leaves (1)
1
Amapola
Petal
Internal (D)
Infusion (1)
1
Pino Rosa Ruda Malva real Calaminta, hierba buena de pastor Kamamila, manzanilla Milamores, valeriana
Bud Petal Aerial part Aerial part Flowered aerial part Inflorescence
Internal (F) Internal (D) Internal (D) External (I) Internal (I)
Decoction Decoction Decoction Bath with Decoction
1 1 1 1 1
Internal (D)
Infusion (4)
4
Aerial part
Internal (Lk)
Infusion (1)
1
Kamamila, manzanilla Té de las peñas, té de roca Té, té de la reina Kamamila, manzanilla Té de las peñas, té de roca Te, té de tierra
Fruit
External (F) External (F)
Maceration with alcohol for 1 mounth, and take 15–20 drops three times a day every day (2) Maceration with alcohol for 9 days and then massage or put cloths soaked in this alcohol (1) Boiled in poultice (1)
FU TFU
External (F)
(1) (1) (1) decoction (1) (1)
1
5
6
1 1 11
9
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Table 2 (continued ) Affection
Plant (Family, voucher specimen)
Popular name
Part used
Administration Preparation (number of use reports)
Chelidonium majus L. (Papaveraceae, 18711) Cynoglossum officinale L. (Boraginaceae, 21119) Galium verum L. ssp. verum (Rubiaceae, 21992) Helichrysum stoechas (L.) Moench ssp. stoechas (Asteraceae, 21250)
Iodobelarra, celidonia Lengua de perro
Stem, leaf
Internal (F)
Infusion (1)
1
Aerial part
Internal (I)
Decoction for 3 times/day (1)
1
Whole plant
Internal (I)
Decoction (1)
1
Inflorescence
Internal (D)
Infusion (1)
1
Inflorescence, leaf Whole plant Leaf
Internal (I)
Infusion (1)
1
Internal (I) Internal (F)
Decoction or comestible (1) Infusion (1)
1 1
Gineceo
Internal (D)
Infusion (1)
1
Pino
Leaf
Internal (F)
1
Manzanilla, manzanilla del monte Auxina, oxina
Inflorescence
Internal (D)
Go to a pine forest and breathe or vapor with decoction (1) Infusion (3)
3
Aerial part
Internal (F)
Infusion (2)
2 21
Lavandula latifolia Medicus (Lamiaceae, 21579) Malva sylvestris L. (Malvaceae, 18748) Mentha suaveolens Ehrh. (Lamiaceae, 18803) Papaver rhoeas L. (Papaveraceae, 21881) Pinus sylvestris L. (Pinaceae, 18798) Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (Asteraceae, 18775) Urtica dioica L. (Urticaceae, 19652)
Galium oloroso, mata de miel Hierba tripera, manzanilla, manzanilla fina Espliego, lavanda Malva Kukuxobelarra, menda, menta Amapola
FU TFU
F: fresh; D: dry; I: without distinction; FU: frequency of uses; TFU: Total of frequency of uses.
COX-1 inhibiting properties, decreasing the production of PGE2 in cells. Natural antioxidants have an important role in human health as they are considered molecules that exert protective effects against oxidative stress, inflammation and neurodegenerative diseases. In relation with this, a study on antioxidant capacity of sixteen plants from Spanish traditional medicine showed that alcoholic and aqueous extracts of aerial parts of J. glutinosa had free radical scavenging effects in terms of reducing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (Lopez et al., 2008). Some compounds detected in J. glutinosa previously demonstrated antioxidant properties in other studies involving other plant species; that is the case of the monoterpene borneol (Horvathova et al., 2012). Other authors verified that borneol reversed oxygen-glucose deprivation followed by reperfusion induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential dissipation in cortical neurons (Liu et al., 2011). Several studies have also demonstrated that flavonoids are metabolites with antioxidant properties (Rubio et al., 1995; Villaescusa et al., 1995). For instance, kaempferol showed protective effects against endothelial damage and its mechanism may be associated with an improvement in nitric oxide production and a decrease in asymmetric dimethylarginin levels (Xiao et al., 2009). These compounds, along with pharmacological spectrum mentioned above, could support the use of infusion from J. glutinosa for the treatment of headache and to clear the mind. S. chamaecyparissus ssp. squarrosa is an aromatic dwarf shrub, native to the western and central Mediterranean and commonly known as ‘manzanilla del monte’. The flowerheads are used in traditional medicine because of its antispasmodic, analgesic, antiinflammatory, neurological problems and psychiatric diseases Spain: Andalusia, Castile-La Mancha, Catalonia, Navarra, and Valencian Community (Akerreta, 2009 and references cited therein). In the same way as J. glutinosa, many scientific articles have confirmed these pharmacological activities, such as analgesic (Almeida et al., 2001), anti-inflammatory (Giner et al., 1986, 1998; Rios et al., 1989; Sala et al., 2000), CNS depressant effect (Giner et al., 1988), spasmogen agonist, and antioxidant (Lopez et al., 2008), and their correlation with the phytochemical composition: acetylenes, flavonoids, essential oils, monoterpenoids, sesquiterpenoids and triterpenoids (Calvo et al., 2013).
S. chamaecyparissus hexanic extracts have a spasmolytic effect on a variety of smooth muscle preparations (Giner et al., 1989). The antagonism to histamine and to serotonin of chloroformic and polar extracts could explain, in part, the anti-inflammatory effects on carrageenan-induced rat paw edema, because both agonists are known mediators of the inflammatory process (Giner et al., 1896). The non-polar extracts of S. chamaecyparissus were potent antagonists of the thermic analgesia test; the former extract being also active in the mechanical analgesia test. The chloroformic extract and, to a lesser extent, the ethyl acetate extract and lyophilized infusion demonstrated noteworthy activity as antiinflammatory agents (Giner et al., 1988). Alemida et al. (2001) published a global review on plant analgesic activity, with special emphasis on those found in different parts of the world, which act on the central nervous system. One hundred and sixty six plants belonging to 79 families were reported, including among them, the dried aerial parts of S. chamaecyparissus from Spain. Pharmacological and phytochemical studies described above could provide the basis to validate the safety and efficacy of the infusion for headache and nervousness and its subsequent approval for approval by Official International Agencies.
4. Concluding remarks The present study is the first one in Navarra to focus on plants for neurological and mental disorders. This is the first step in pharmaceutical bioprospection, and these data may be the starting point for further research aimed at obtaining products for therapeutical uses. Twenty percent of the medicinal plants used in Navarra for neurological and mental disorders have been pharmacologically validated by Official International Organisms. Of the remaining 80%, the authors highlight Chamaemelum nobile, Jasonia glutinosa, and Santolina chamaecyparissus ssp. squarrosa for its validation. Numerous ethnobotanical, phytochemical and pharmacological studies suggest that these medicinal plants have proved to be effective for neurological and mental disorders. The evidence of these folk uses could be the key information in simplified procedures established by the European Union for the registration of herbal medicinal products based on traditionally used plants,
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Giner, R.M., Ríos, J.L., Villar, A., 1988. CNS depressant effects, anti-inflammatory activity and anti-cholinergic actions of Santolina chamaecyparissus extracts. Phytother. Res. 2, 37–41. Giner, R.M., Ríos, J.L., Villar, A., 1989. Inhibitory effects of Santolina chamaecyparissus extracts against spasmogen agonists. J. Ethnopharmacol. 27, 1–6. Guillen, M.D., Ibargoitia, M.L., 1996. Volatile components obtained from the leaves of Jasonia glutinosa. Food Chem. 56, 155–158. Guimarães, R., Barros, L., Dueñas, M., Calhelha, R.C., Carvalho, A.M., Santos-Buelga, C., Queiroz, M.J.R.P., Ferreira, I.C.F.R., 2013. Nutrients, phytochemicals and bioactivity of wild Roman chamomile: a comparison between the herb and its preparations. Food Chem. 136, 718–725. Horvathova, E., Kozics, K., Srancikova, A., Hunakova, L., Galova, E., Sevcovicova, A., Slamenova, D., 2012. Borneol administration protects primary rat hepatocytes against exogenous oxidative DNA damage. Mutagenesis 27, 581–588. Liu, R., Zhang, L., Lan, X., Li, L., Zhang, T.T., Sun, J.H., Du, G.H., 2011. Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor kappB signaling pathway. Neuroscience 176, 408–419. Lopez, V., Akerreta, S., Casanova, E., Garcia-Mina, J.M., Cavero, R.Y., Calvo, M.I., 2008. Screening of spanish medicinal plants for antioxidant and antifungal activities. Pharm. Biol. 46, 602–609. Ma, C., Winsor, L., Daneshtalab, M., 2007. Quantification of spiroether isomers an herniarin of different parts of Matricaria matricarioides and flowers of Chamaemelum nobile. Phytochem. Anal. 18, 42–49. Menendez-Baceta, G., Aceituno-Mata, L., Molina, M., Reyes-García, V., Tardío, J., Pardo-de-Santayana, M., 2014. Medicinal plants traditionally used in the northwest of the Basque Country (Biscay and Alava), Iberian Peninsula. J. Ethnopharmacol. 152, 113–134. Payyappallimana, U., 2010. Role of traditional medicine in primary health care: an overview of perspectives and challenges. Yokohama J. Soc. Sci. 14, 57–77. Real Farmacopea Española 5th edition. Ministerio de Sanidad y Consumo. Madrid. 2015. Rios, J.L., Giner, R.M., Villar, A., 1989. Isolation and identification of an antiinflammatory principle from Santolina chamaecyparissus. Phytother. Res. 3, 212–214. Romero, M.A.G., Castillo, L.V., Lanza, A.M.D., Bricio, J.M.A., Monzon, C.A.S., Perucha, J.S., 2003. Volatile composition of Jasonia glutinosa D.C. Z. Naturforschung C 58, 804–806. Rubio, B., Villaescusa, L., Diaz, A.M., Fernandez, L., Martin, T., 1995. Flavonol glycosides from Scolymus hispanicus and Jasonia glutinosa. Planta Med. 61, 583. Rucker, G., Mayer, R., Kang, R.L., 1989. Hydroperoxides from the blossoms of Roman camomile (Anthemis nobilis L.). Arch. Pharm. 322, 821–826. Sala, A., Recio, M.C., Giner, R.M., Máñez, S., Rios, J.L., 2000. Anti-phospholipase A2 and anti-inflammatory activity of Santolina chamaecyparissus. Life Sci. 66, 35–40. Sanchez-Martinez, R., Villaescusa-Castillo, L., Bernabe, M., Diaz-Lanza, A.M., 2000. Two new eudesmane alcohols from Jasonia glutinosa. Z. Naturforschung C 55, 693–696. Tschan, G.M., Konig, G.M., Wright, A.D., Stichert, O., 1996. Chamaemeloside, a new flavonoid glycoside from Chamaemelum nobile. Phytochemistry 41, 643–646. Villaescusa, L., Díaz, A.M., Martín, T., Gasquet, M., Delmas, F., Balansard, G., 1996. Preliminary screening of antiprotozoal activity of Jasonia glutinosa aerial parts. Pharm. Biol. 34, 303–304. WHO, 1999–2010. WHO Monographs on Selected Medicinal Plants, Vol. 1–5. World Health Organization, Geneva. WHO, 2001. 〈www.who.int/whr/2001/media_centre/en/whr01_fact_sheet1_en. pdf〉. Xiao, H.B., Jun, F., Lu, X.Y., Chen, X.J., Chao, T., Sun, Z.L., 2009. Protective effects of kaempferol against endothelial damage by an improvement in nitric oxide production and a decrease in asymmetric dimethylarginine level. Eur. J. Pharmacol. 616, 213–222. Zeggwagh, N.A., Michel, J.B., Eddouks, M., 2013. Vascular effects of aqueous extract of Chamaemelum nobile: in vitro pharmacological studies in rats. Clin. Exp. Hypertens. 35, 200–206.
Contents lists available at ScienceDirect
Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep
Medicinal plants used for neurological and mental disorders in Navarra and their validation from official sources María Isabel Calvo a,n, Rita Yolanda Cavero b a b
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain Department of Environmental Biology, Faculty of Sciences, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain
art ic l e i nf o
a b s t r a c t
Article history: Received 3 February 2015 Received in revised form 17 April 2015 Accepted 18 April 2015 Available online 25 April 2015
Ethnopharmacological relevance: This paper provides important ethnopharmacological information on plants used in neurological and mental disorders in Navarra. Material and methods: Information was collected using semi-structured ethnobotanical interviews with 667 informants in 265 locations. In order to confirm the pharmacological validation of the uses claimed by the informants, monographs from Official International Agencies (ESCOP, Commission E, WHO and EMA) were reviewed. A literature review was conducted focusing on the plants that were widely used but had no published monograph. Results: A total of 172 pharmaceutical uses were reported, for 46 plants and 26 families, mainly represented by Lamiaceae (15%), Asteraceae (13%), Rosaceae and Rutaceae (7%, each one), and Clusiaceae, Malvaceae, Papaveraceae and Urticaceae (4%, each one). The most frequently used parts were inflorescence (39%), flowered aerial parts (16%), and aerial parts (13%), followed by inflorescence bract (8%) and leaves (7%). Nine out of 46 plants (20%) and 81 of 172 uses (47%), have already been pharmacologically validated. The remaining 37 plants (of total 46, 80%) have been reported for neurological and mental disorders and need to be screened through standard pharmacological and clinical procedures for their activities. The most used species are Chamaemelum nobile (L.) All., Jasonia glutinosa (L.) DC., and Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman, in all cases the administration as infusion. Conclusions: Data indicate a high degree of plants knowledge in Navarra regarding neurological and mental disorders. The present study constitutes a good basis for further phytochemical and pharmacological research of C. nobile, J. glutinosa and S. chamaecyparissus, which could be of interest in the design of new inexpensive, effective and safe drugs. & 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Nervous system Ethnopharmacology Chamaemelum nobile Jasonia glutinos Santolina chamaecyparissus Spain
1. Introduction Traditional medicine is used worldwide and it is of great economic importance in the 21st century (Bussmann, 2013). Among the positive aspects of traditional medicine, researchers have mentioned diversity, flexibility, accessibility, relevance in developing countries, increasing popularity in developed countries, relative low cost, few side effects of medicinal plants (Payyappallimana, 2010). The World Health Organization (WHO) estimates that over one billion people worldwide suffer from illnesses of the central nervous system. Besides injuries of the brain and the spinal cord, these include a large number of neurological or mental illnesses. Neurological disorders are diseases of the central and peripheral nervous system. These disorders include epilepsy, Alzheimer disease and other dementias, migraine and other headache disorders, n
Corresponding author. Tel.: þ 34 948425600x806239; fax: þ 34 948425740. E-mail address: [email protected] (M.I. Calvo).
http://dx.doi.org/10.1016/j.jep.2015.04.035 0378-8741/& 2015 Elsevier Ireland Ltd. All rights reserved.
multiple sclerosis, Parkinson's disease, neuroinfections, brain tumors and traumatic disorders of the nervous system. Mental disorders, on the other hand, are psychiatric illnesses or diseases, (i.e. anxiety, depressive and schizophrenia), which appear primarily as abnormalities of thought, feeling or behavior, producing either distress or impairment of function. These illnesses not only cause great human suffering, but are also linked with enormous costs – stays in hospital, loss of working hours, early retirement and, in many cases, life-long care. These social, ethical and economic reasons call for the urgent improvement of medical research in this field (WHO, 2001). The investigation carried out by our research group in Navarra began in 2003 and continues to the present. The high number of plants collected to date has allowed the publication of several manuscripts for various affections: digestive (Calvo et al., 2013), dermatological (Cavero et al., 2013), cardiovascular (Calvo and Cavero, 2014), respiratory (Cavero and Calvo, 2014) and musculoskeletal diseases (Cavero and Calvo, 2015). Following on from this, the aims of the present paper are: i) to collect information
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about plant species used for problems associated with the nervous system; ii) to analyze these ethnopharmacological data; iii) to look for coincidences of the reported uses in the literature in order to validate them from a pharmacological viewpoint; and, iv) to propose highly plants reported without bibliographic validation.
2. Material and methods 2.1. Study area Navarra is a territory of 10,421 km2 placed to the North of the Iberian Peninsula, where three zones can be differed: the Mountain on the North, the Riverside on the South, and both separated by a zone of transition, the Middle Navarra. There are two macrobioclimates, Temperate and Mediterranean. These factors provide a great diversity of plant communities and a rich flora (2,650 vascular plants) (Cavero et al., 2013).
study, medicinal plants used for neurological and mental disorders were analyzed. To confirm the reported uses by participants in the study, the literature was reviewed in order to carry out a pharmacological validation in reported plants, using monographs (sometimes linked to databases) from official sources: the European Scientific Cooperative on Phytotherapy (ESCOP, 2003–2009), German Commission E (Blumenthal et al., 2000), World Health Organization (WHO, 1999–2010), European Medicines Agency (www.ema. europa.eu/ema/index), European Pharmacopoeia (2013) and Real Farmacopea Española (Real Farmacopea Española, 2015) monographs. These monographs are responsible for evaluating the quality, safety and efficacy of herbs. A literature review was carried out for the plants that were reported to be in widespread use, for which no monograph exists.
2.2. Methodology
3. Results and discussion
Information was collected using semi-structured ethnobotanical interviews as a technique for data collection from informants. Interviews were practiced from 2003 to 2014. Native people, 667 informants (mean age470 years) of 265 locations, were interviewed in Basque and Castilian language, both official languages of Navarra. In the field work we noted for each species the local name, place and collection method, drying and preservation system, parts or organs used and method of preparation, dosage and administration. Voucher samples are kept in the PAMP Herbarium at the Faculty of Science (University of Navarra). In the present
3.1. Botanical information A total of 172 pharmaceutical uses were reported, belonging to 46 plants (78% native and 22% introduced species from other continents, or other European regions). The complete catalog of the ethnoflora of the surveyed territory is given in Akerreta (2009). The 46 medicinal plants belong to 26 families, mainly represented by Lamiaceae (15%), Asteraceae (13%), Rosaceae and Rutaceae (7%, each one), and Clusiaceae, Malvaceae, Papaveraceae and Urticaceae (4%, each one).
Table 1 Plants with validation from official sources. Plant (Family, voucher specimen)
Popular name
Crataegus monogyna Jacq. (Rosaceae, 18723) Humulus lupulus L. (Cannabaceae, 21144)
Ph Administration Preparation
Popular use (number of use FU Monograph reports)
Ellori zuria, espino, Flower espino blanco
A, B
Internal (I)
Infusion
Lupibelarra, lúpulo
Female inflorescence
A
External (D)
To put inside the pillow.
Anxiety, for nerves, tranquilizer and relaxing (5), for sadness (1) To sleep better (3)
San Juan belarra, hipérico, hierba de San Juan Lavandula angustifolia Mill Espliego, lavanda ssp.angustifolia (Lamiaceae, 21575) Melissa officinalis L. Melisa (Lamiaceae, 18688) Rosmarinus officinalis L. Romero (Lamiaceae, 21655)
Flowered aerial part, flower Flowed aerial part
A, B
Internal (D) Internal (D)
Infusion Infusion
A, B
Internal (D)
Leaf, aerial part Flower Aerial part, flowered aerial part
A, B A, B
Sambucus nigra L. ssp. Astunpa, intsusa, nigra (Adoxaceae, 18661) sabuko, saúco
Internal bark, leaf
A, B
Inflorescence Inflorescence
Hypericum perforatum L. (Clusiaceae, 21559)
Tilia cordata Mill. Tilo (Tiliaceae, 22028) Tilia platyphyllos Scop. ssp. Tilo platyphyllos (Tiliaceae, 18752)
Part used
Inflorescence bract, inflorescence
6 1,3,4
3 2,4
To lift the spirits, depression (6)
6 1,2,3,4
Infusion
Tranquilizer (2)
2 1,2,3,4
Internal (I)
Infusion
6 1,4
External (I)
5 3
Internal (I) External (I)
To rub with the macerated in wine or alcohol, or with wine decoction, vapors. Infusion or maceration in wine Ointment with lard and wax, roasted in poultice Poultice or ointment with lard and wax.
Tranquilizer and relaxing (5), depression (1) Analgesic (3)
Stimulant (2) Analgesic (2)
3 4 3a
A
Internal (I) Internal (D)
Smoke inhalation Infusion
Analgesic (2) For nerves and to relax (4)
3 4 4
A
Internal (D)
Infusion
For nerves, tranquilizer and 45 4 relaxing, to sleep better (45)
Ph: Pharmacopeia; A: European Pharmacopoeia; B: Real Farmacopea Española; F: fresh; D: dry; I: without distinction; 1: ESCOP monograph; 2: German Commission E monograph; 3. WHO monograph; 4: EMA monograph. a
Different part used; FU: frequency of uses.
M.I. Calvo, R.Y. Cavero / Journal of Ethnopharmacology 169 (2015) 263–268
The most frequently used parts were inflorescence (39%), flowered aerial parts (16%), aerial parts (13%), inflorescence bract (8%), leaves (7%), flowers (5%), fruits (3%) and petals (2%). Plants were used dry (61%), fresh (19%), or either (18%) and lost knowledge (2%) for administration in different forms. The percentage of internal uses was five times higher than that for external uses (84% and 16%, respectively), and the most important forms of preparation were infusion (86%), decoction (9%), and in lower proportions, maceration (3%), and vapors (2%); for external uses, the most important form were poultices (43%), maceration (29%), and ointment (11%) 3.2. Pharmacopoeias references Nine out of 46 plants (20%) and 81 of 172 total uses (47%), have already been pharmacologically validated for neurological and mental diseases by ESCOP, Commission E, WHO and EMA Monographs (Table 1). It is important to highlight that Hypericum perforatum L., and Lavandula angustifolia Mill ssp.angustifolia (two of nine plants, 22%) have monographs in the four agencies taken into consideration. All of plants cited in Table 1 have monograph in the European Pharmacopoeia and/or Real Farmacopea Española. 3.3. Futher pharmacological data The remaining 37 of 46 plants (80%) and 91 of 172 uses (53%) were reported for nervous system troubles and need to be screened through standard scientific procedures for their actions (Table 2). We found that the most widely treated affections fell into six pathological categories: analgesic (14%), antidepressant (5%), to clear the mind (7%), headache (41%), insomnia (10%) and nervousness (23%). In this study, the results showed 9 plants as analgesic (agents that alleviate pain without causing anesthesia), being the most cited Malva sylvestris L. (3 uses of 91 total uses, 3%) and Urtica dioica L. (2 uses, 2%). The infusion of flowered aerial part from Hypericum androsaemum L. was cited as antidepressant for sadness (emotional pain associated with, or characterized by feelings of disadvantage, loss, despair, helplessness and sorrow) or “to lift up the spirit” (2 uses, 2%). With the same therapeutic indication, the maceration in anisette from Prunus spinosa L. was also recopilated (2 uses, 2%). The most reported application to clear the mind (4 uses, 4%) was the infusion of flowered aerial part from Jasonia glutinosa (L.) DC. Headache or cephalagia is a pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The most widely cited plants for this affection were J. glutinosa (12 uses of 91 total uses, 13%), Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (11 uses, 12%), Chamaemelum nobile (L.) All. (5 uses, 5%) and Verbena officinalis L. (2 uses, 2%). The first three plants were administered internally in infusion and the last one, V. officinalis, a poultice using white egg as excipient. Eight plants were reported to sleep aid or insomnia. The inflorescence of Lavandula latifolia Medicus was the most important plant (2 uses, 2%) in two different form of administration, infusion or introduced into the pillow overnight to smell it. It is important to highlight the importance of infusions from C. nobile (4 uses, 4%), S. chamaecyparissus (3 uses, 3%) and U. dioica (2 uses, 2%) as tranquilizers for nervousness. In summary, the most widely cited plants for nervous system problems belong to the Asteraceae family: C. nobile (10 uses, 11%), J. glutinosa (16 uses, 18%) and S. chamaecyparissus ssp. squarrosa (14 uses, 15%).
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C. nobile, commonly known as ‘manzanilla’ or ‘kamamila’, is a perennial herb. It is native to Southwest Europe (France, Spain and Portugal) but the plant is present all over Europe, North Africa and Southwest Asia. The plant is cultivated mainly in England, Belgium, France, Germany, Hungary, Poland, Bulgaria, Egypt and Argentina. Although ‘manzanilla’ flowerheads are described as antiseptic, antibiotic, disinfectant, bactericidal, fungicidal and vermifuge. It has been used for centuries as anti-inflammatory, antioxidant, mild astringent, mild sedative, antispasmodic, antibacterial and healing medicine (Guimarães et al., 2013), the European Medicines Agency (EMA-HMPC, 2011) has only approved the traditional use of oral dosage forms (decoctions and infusions) for the symptomatic treatment of mild gastrointestinal spasmodic affections such as bloating and flatulence, and for the inflammation of the oropharyngeal cavity. The uses of ‘manzanilla’ that are described in the Commission E monograph (Blumenthal et al., 1998) are similar. Regarding neurological and mental affections, a review of literature from etnopharmacological studies has showed that C. nobile is used in different regions of Spain: Basque Country, Cantabria, Navarra and Principality of Asturias (Akerreta, 2009, and references cited therein; Cavero et al., 2011a; MenendezBaceta et al., 2014). Additionally, one ethnopharmacological references was found in Portuguese Republic (Camejo-Rodrigues, 2001). Different classes of bioactive constituents are present in ‘manzanilla’, including volatile oil and sesquiterpenes (Farhoudi, 2013), hydroperoxides (Rucker et al., 1989), flavonoids, catechins, phenolic acids and coumarins (Tschan et al., 1996), polyacetylenes (Ma et al., 2007), triterpenes and steroids (Fauconnier et al., 1996). This chemical composition may be responsible for spasmolytic, anxiolitic and vascular effect of ethanolic and aqueous extract (Dooraghi et al., 2010; Zeggwagh et al., 2013), which could explain its applications in nervous system problems, like as nervousness and headaches (Carnat et al., 2004). Jasonia glutinosa is very popular as a stomachic as well as a component in preparations showing beneficial effects such as antispasmodic and anti-inflammatory drug in relation to nervous system problems Iberian Peninsula, Spain: Andalusia, Aragon, Cantabria, Catalonia, Navarra and Valencian Community (Akerreta, 2009 and references cited therein; Calvo et al., 2011; Cavero et al., 2011a, 2011b). Nonsteroidal anti-inflammatory drugs (NSAIDs), along with analgesics, are considered a first-line treatment for sufferers of mild to moderate headache pain. NSAIDs, such as ibuprofen and naproxen, relieve pain by inhibiting prostaglandins, compounds implicated in the inflammatory responses. These drugs help reduce the swelling associated with the pain of headaches. In various phytochemical studies performed on J. glutinosa it was found to contain essential oils (Guillen and Ibargoitia, 1996; Romero et al., 2003), flavonoids (Rubio et al., 1995) and sesquiterpenoids (Bermejo et al., 2002; Sanchez-Martinez et al., 2000). Sesquiterpenes and flavonoids are secondary metabolites widely distributed in the higher plant kingdom and are known to show diverse biological and pharmacological actions. For this reason, these compounds have been evaluated for their in vitro antiinflammatory activity in cellular systems generating cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) metabolites. Both types of compounds showed a significant effect on thromboxane B2 (TXB2)-release induced by calcium ionophore in human platelets, although with less potency than the reference drug ibuprofen (Villaescusa et al., 1996). In addition, the sesquiterpenes, such as lucinone, glutinone, epi-kutdtriol and kutdtriol, showed antiinflammatory properties in a previous work with peritoneal mice macrophages (Bermejo et al., 2002). All sesquiterpenes exerted
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Table 2 Plant without validation from official sources. Affection
Plant (Family, voucher specimen)
Popular name
Part used
Administration Preparation (number of use reports)
Analgesic
Allium sativum L. (Liliaceae, 21718)
Ajo
Bulb
Internal (F)
Citrus limon (L.) Burm. (Rutaceae, 21189)
Limón
Fruit
External (F)
Juglans regia L. (Juglandaceae, 18683)
Noguera, nogal
External (F)
Laurus nobilis L. (Lauraceae, 21715) Malva sylvestris L. (Malvaceae, 18748)
Laurel Malva
Plantago lanceolata L. (Plantaginaceae, 18716) Triticum aestivum L. (Poaceae, 18797) Urtica dioica L. (Urticaceae, 19652)
External bark, leaf Leaf Aerial part, flower Leaf
Plantinabelarra, cincovenas, llantén Trigo Fruit (Seed) Auxina, oxina, ortiga Aerial part
Vitis vinifera L. (Vitaceae, 21809)
Ardoaegosite, uva, vid Milazulo haundi, hipérico Elorri beltza, patxaran, arañones Berbenabelarra, kolpebelarra, verbena Armuelle
Antidepressant Hypericum androsaemum L. (Clusiaceae, 21551) Prunus spinosa L. (Rosaceae, 21969) Verbena officinalis L. (Verbenaceae, 21770) Clear the mind Atriplex patula L. (Amaranthaceae, 21168) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Jasonia glutinosa (L.) DC. (Asteraceae, 21252) Headache Bidens aurea (Aiton) Sherff (Asteraceae, 19675) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Jasonia glutinosa (L.) DC. (Asteraceae, 21252) Jasonia tuberosa (L.) DC. (Asteraceae, 18772) Parietaria judaica L. (Urticaceae, 21723) Petroselinum crispum (Mill.) Fuss (Apiaceae, 22061) Polygonum lapathifolium L. (Polygonaceae, 21908) Rosa sp. (Rosaceae, 18726) Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (Asteraceae, 18775) Thymus vulgaris L. (Lamiaceae, 21713) Verbena officinalis L. (Verbenaceae, 21770) Insomnia
Nervousness
Centranthus ruber (L.) DC. ssp. ruber (Caprifoliaceae, 21765) Citrus sinensis (L.) Osbeck (Rutaceae, 22514) Lavandula latifolia Medicus (Lamiacaea, 21579) Nerium oleander L. ssp. oleander (Apocynaceae, 18785) Papaver rhoeas L. (Papaveraceae, 21881) Pinus sylvestris L. (Pinaceae, 18798) Rosa sp. (Rosaceae, 18726) Ruta montana (L.) L. (Rutaceae, 21997) Alcea rosea L. (Malvaceae, 21821) Calamintha nepeta (L.) Savi ssp. nepeta (Lamiaceae, 21572) Chamaemelum nobile (L.) All. (Asteraceae, 21222) Centranthus ruber (L.) DC. ssp. ruber (Caprifoliaceae, 21765)
2
1
1
Boiled in poultice with olive oil (1) Boiled in poultice or ointment with lard and wax (3) Boiled in poultice (1)
1 3
External (I) Internal (F), external (I) Internal (F)
Poultice with egg or olive oil (1) Infusion for 3 days (1), to rub (1)
1 2
Burn wine and take (1)
1 13
Flowered aerial part Fruit
Internal (F, I)
Infusion (2)
2
Internal (F)
Maceration in anisette (2)
2
Flowered aerial part
Internal (I)
Infusion (1)
1
Leaf
Internal (F)
Infusion or comestible (1)
1
Inflorescence
Internal (D)
Infusión (1)
1
Flowered aerial part Aerial part
Internal (D)
Infusion (4)
4
Internal (F)
Infusión (1)
1
Inflorescence
Internal (D)
Infusion (5)
5
Internal (D)
Infusion (12)
12
Internal (D)
Decoction (1)
1
Paretabelarra, parietaria, rompepiedras Perejil
Flowered aerial part Flowered aerial part Aerial part
Internal (F)
Decoction and take a gulp for 20 days (1)
1
Leaf
External (F)
1
Pimienta acuática
Aerial part
Internal (I)
Poultice with decoction for three days, three times daily (1) Infusion for 3 times/day (1)
Rosa Manzanilla, manzanilla del monte Tomillo
Fruit, petal Inflorescence
Internal (D) Internal (D)
Decoction (1) Infusion (11)
Flowered aerial part Aerial part
External (I)
Soak the head with the decoction (1)
1
Berbenabelarra, kolpebelarra, verbena Milamores, valeriana Inflorescence
External (F)
Poultice with white of eggs (2)
2 37
Internal (Lk)
Infusion (1)
1
Naranjo
Fruit
Internal (F)
Decoction and taken before bedtime (1)
1
Espliego, lavanda
Inflorescence
Infusion (1), to put inside the pillow (1)
2
Adelfa
Leaf
Internal (I), external (D) External (F)
Rub the head with two leaves (1)
1
Amapola
Petal
Internal (D)
Infusion (1)
1
Pino Rosa Ruda Malva real Calaminta, hierba buena de pastor Kamamila, manzanilla Milamores, valeriana
Bud Petal Aerial part Aerial part Flowered aerial part Inflorescence
Internal (F) Internal (D) Internal (D) External (I) Internal (I)
Decoction Decoction Decoction Bath with Decoction
1 1 1 1 1
Internal (D)
Infusion (4)
4
Aerial part
Internal (Lk)
Infusion (1)
1
Kamamila, manzanilla Té de las peñas, té de roca Té, té de la reina Kamamila, manzanilla Té de las peñas, té de roca Te, té de tierra
Fruit
External (F) External (F)
Maceration with alcohol for 1 mounth, and take 15–20 drops three times a day every day (2) Maceration with alcohol for 9 days and then massage or put cloths soaked in this alcohol (1) Boiled in poultice (1)
FU TFU
External (F)
(1) (1) (1) decoction (1) (1)
1
5
6
1 1 11
9
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267
Table 2 (continued ) Affection
Plant (Family, voucher specimen)
Popular name
Part used
Administration Preparation (number of use reports)
Chelidonium majus L. (Papaveraceae, 18711) Cynoglossum officinale L. (Boraginaceae, 21119) Galium verum L. ssp. verum (Rubiaceae, 21992) Helichrysum stoechas (L.) Moench ssp. stoechas (Asteraceae, 21250)
Iodobelarra, celidonia Lengua de perro
Stem, leaf
Internal (F)
Infusion (1)
1
Aerial part
Internal (I)
Decoction for 3 times/day (1)
1
Whole plant
Internal (I)
Decoction (1)
1
Inflorescence
Internal (D)
Infusion (1)
1
Inflorescence, leaf Whole plant Leaf
Internal (I)
Infusion (1)
1
Internal (I) Internal (F)
Decoction or comestible (1) Infusion (1)
1 1
Gineceo
Internal (D)
Infusion (1)
1
Pino
Leaf
Internal (F)
1
Manzanilla, manzanilla del monte Auxina, oxina
Inflorescence
Internal (D)
Go to a pine forest and breathe or vapor with decoction (1) Infusion (3)
3
Aerial part
Internal (F)
Infusion (2)
2 21
Lavandula latifolia Medicus (Lamiaceae, 21579) Malva sylvestris L. (Malvaceae, 18748) Mentha suaveolens Ehrh. (Lamiaceae, 18803) Papaver rhoeas L. (Papaveraceae, 21881) Pinus sylvestris L. (Pinaceae, 18798) Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman (Asteraceae, 18775) Urtica dioica L. (Urticaceae, 19652)
Galium oloroso, mata de miel Hierba tripera, manzanilla, manzanilla fina Espliego, lavanda Malva Kukuxobelarra, menda, menta Amapola
FU TFU
F: fresh; D: dry; I: without distinction; FU: frequency of uses; TFU: Total of frequency of uses.
COX-1 inhibiting properties, decreasing the production of PGE2 in cells. Natural antioxidants have an important role in human health as they are considered molecules that exert protective effects against oxidative stress, inflammation and neurodegenerative diseases. In relation with this, a study on antioxidant capacity of sixteen plants from Spanish traditional medicine showed that alcoholic and aqueous extracts of aerial parts of J. glutinosa had free radical scavenging effects in terms of reducing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (Lopez et al., 2008). Some compounds detected in J. glutinosa previously demonstrated antioxidant properties in other studies involving other plant species; that is the case of the monoterpene borneol (Horvathova et al., 2012). Other authors verified that borneol reversed oxygen-glucose deprivation followed by reperfusion induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential dissipation in cortical neurons (Liu et al., 2011). Several studies have also demonstrated that flavonoids are metabolites with antioxidant properties (Rubio et al., 1995; Villaescusa et al., 1995). For instance, kaempferol showed protective effects against endothelial damage and its mechanism may be associated with an improvement in nitric oxide production and a decrease in asymmetric dimethylarginin levels (Xiao et al., 2009). These compounds, along with pharmacological spectrum mentioned above, could support the use of infusion from J. glutinosa for the treatment of headache and to clear the mind. S. chamaecyparissus ssp. squarrosa is an aromatic dwarf shrub, native to the western and central Mediterranean and commonly known as ‘manzanilla del monte’. The flowerheads are used in traditional medicine because of its antispasmodic, analgesic, antiinflammatory, neurological problems and psychiatric diseases Spain: Andalusia, Castile-La Mancha, Catalonia, Navarra, and Valencian Community (Akerreta, 2009 and references cited therein). In the same way as J. glutinosa, many scientific articles have confirmed these pharmacological activities, such as analgesic (Almeida et al., 2001), anti-inflammatory (Giner et al., 1986, 1998; Rios et al., 1989; Sala et al., 2000), CNS depressant effect (Giner et al., 1988), spasmogen agonist, and antioxidant (Lopez et al., 2008), and their correlation with the phytochemical composition: acetylenes, flavonoids, essential oils, monoterpenoids, sesquiterpenoids and triterpenoids (Calvo et al., 2013).
S. chamaecyparissus hexanic extracts have a spasmolytic effect on a variety of smooth muscle preparations (Giner et al., 1989). The antagonism to histamine and to serotonin of chloroformic and polar extracts could explain, in part, the anti-inflammatory effects on carrageenan-induced rat paw edema, because both agonists are known mediators of the inflammatory process (Giner et al., 1896). The non-polar extracts of S. chamaecyparissus were potent antagonists of the thermic analgesia test; the former extract being also active in the mechanical analgesia test. The chloroformic extract and, to a lesser extent, the ethyl acetate extract and lyophilized infusion demonstrated noteworthy activity as antiinflammatory agents (Giner et al., 1988). Alemida et al. (2001) published a global review on plant analgesic activity, with special emphasis on those found in different parts of the world, which act on the central nervous system. One hundred and sixty six plants belonging to 79 families were reported, including among them, the dried aerial parts of S. chamaecyparissus from Spain. Pharmacological and phytochemical studies described above could provide the basis to validate the safety and efficacy of the infusion for headache and nervousness and its subsequent approval for approval by Official International Agencies.
4. Concluding remarks The present study is the first one in Navarra to focus on plants for neurological and mental disorders. This is the first step in pharmaceutical bioprospection, and these data may be the starting point for further research aimed at obtaining products for therapeutical uses. Twenty percent of the medicinal plants used in Navarra for neurological and mental disorders have been pharmacologically validated by Official International Organisms. Of the remaining 80%, the authors highlight Chamaemelum nobile, Jasonia glutinosa, and Santolina chamaecyparissus ssp. squarrosa for its validation. Numerous ethnobotanical, phytochemical and pharmacological studies suggest that these medicinal plants have proved to be effective for neurological and mental disorders. The evidence of these folk uses could be the key information in simplified procedures established by the European Union for the registration of herbal medicinal products based on traditionally used plants,
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