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Indian Pennywort
C H A P T E R
32 Indian Pennywort Shahzia Yousaf1, Muhammad Asif Hanif1, Rafia Rehman1, Muhammad Waqar Azeem1, Anca Racoti2 1
Department of Chemistry, University of Agriculture, Faisalabad, Pakistan; 2 The National Institute for Research & Development in Chemistry and Petrochemistry e ICECHIM, Bucharest, Romania
O U T L I N E 1. Botany 1.1 Introduction 1.2 History/Origin 1.3 Location/Demography 1.4 Botany, Morphology, Ecology
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2. Chemistry
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3. Postharvest
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4. Processing
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5. Value Addition
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6. Uses
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7. Pharmacological Uses 7.1 Antitumor Activity 7.2 Memory Enhancing Effects 7.3 Cardioprotective Effects 7.4 Immunostimulating Effects 7.5 Mental Retardation Effects 7.6 Antitubercular and Antileprotic Activity
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Medicinal Plants of South Asia https://doi.org/10.1016/B978-0-08-102659-5.00032-X
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Copyright © 2020 Elsevier Ltd. All rights reserved.
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7.7 7.8 7.9 7.10 7.11 7.12 7.13 7.14 7.15 7.16
Wound Healing Effects Effects on Venous Insufficiency Sedative and Anxiolytic Properties Antidepressant Properties Antiepileptic Properties Cognitive and Antioxidant Properties Effects on Gastric Ulcer Antinociceptive and Antiinflammatory Properties Radioprotection Effects Antidiabetic Activity
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8. Side Effects and Toxicity
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References
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1. BOTANY 1.1 Introduction Indian pennywort (Centella asiatica) (Fig. 32.1) is a perennial, clonal, herbaceous plant belonging to Umbelliferae (Apiaceae) family that is found all over India, growing in damp areas up to an altitude of 1800 m. It occurs commonly in subtropical and tropical countries, including parts of Pakistan, India, Madagascar, Sri Lanka, Eastern Europe, South Africa, and
FIGURE 32.1
Dried Indian pennywort.
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the South Pacific. Twenty species that are closely resembled to C. asiatica propagate in most parts of the tropic or wet pantropical parts like rice paddies, also in rocky places and higher altitudes (Bown, 1995). It is a tasteless, weakly scented plant that more frequently flourishes in waterrich places. Its leaves are green, small, fan-shaped with white or light pink to purple flowers, and it has small, elliptical fruit. For medicinal purposes the entire plant is used. It is mostly used for blood purification as well as treating memory improvement (intellect), high blood pressure, and other similar problems. In Ayurveda, C. asiatica is one of the main herbs for activating the nerves and brain cells. To treat emotional disorders, such as depression, hakims use C. asiatica. In Western medicine, in the mid-20th century, C. asiatica and its alcohol extracts were used in the treatment of leprosy (Duggina et al., 2015). C. asiatica was confused earlier with Bacopa monnieri in the Indian market because both were sold by the “Brahmi” name. Later on, the problem was solved by giving a separate name: brahmi for B. monnieri and mandookaparni for C. Asiatic. Due to extensive use at a large scale along with little cultivation, wild species of the plant are disappearing from sight, and attempts have not been made for its revival (Larsen and Olsen, 2007). Due to the same reason, International Union for Conservation of Nature and Natural Resources enlisted it as a rare and threatened plant species. Region-wise common names are gotu kola in Urdu and thankuni in Bengali, mandookparni in Hindi, pegaga in Malay, bekaparanamu in Telgu, vallarai in Tamil, and kodagam in Malayalam.
1.2 History/Origin C. asiatica (Linn), native to Sri Lanka, South Africa, Madagascar, and Malaysia, has been used since ancient times by tribal groups and cultures as a medicinal herb. For about 2000 years, C. asiatic has been a part of Chinese herbal medicines and 3000 years in Indian Ayurvedic system of medicines (Gnanapragasam et al., 2004). In Ayurvedic medicines, mandukaparni is used for the treatment of skin diseases, leprosy, gastric catarrh, elephantiasis, kidney troubles, asthma, bronchitis, and leucorrhoea, while in Chinese herbal medicine, it is used for curing toxic fever and leucorrhoea. In Malaysia, C. Asiatic is used to cure anxiety, eczema, and mental fatigue. It is also eaten as salad when fresh (Goh et al., 1995). Fresh plant extracts have been used for many years by the people of Malay Peninsula and Java for healing wounds, internally and externally. The plant extracts are also an active part of brain tonics for mental impairment. The presence of pentacyclic triterpenes, madecassoside, madecassic acid, asiaticoside, and asiatic acid is responsible for these properties (Jamil et al., 2007).
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1.3 Location/Demography C. asiatic grows all over the tropical and subtropical areas of India up to 600 m altitude. It is also found at an altitude of 1200 m in Mount Abu (Rajasthan, India) and at even more altitude of 1550 m in Sikkim (northeastern Indian state). Sandy loam (60%) type of soil proved to be the utmost choice for regeneration of it, rather than clayey soil (Devkota and Jha, 2009). In the wild, Centella plant is found in wet or moist soils of marshes, swamp, bogs, and along the margins of ponds, lakes, irrigation, streams, and drainage canals of irrigated paddy fields. It is also found in wet pine savannas, flat woods, and palmetto flats, often forming meadows. It grows in water or on land (Hamid et al., 2002). The species is pantropic, found in the United States from Delaware to southern Florida, in West Indies, Mexico, central and southern America, Australia, Sri Lanka, and the Philippines.
1.4 Botany, Morphology, Ecology C. asiatic (L.) is a flat, creeping, stoloniferous, perennial herb, faintly aromatic that grows up to 15 cm height. Stem is glabrous, striated, rooting at nodes. Each node has one to three leaves with a width of 1.5e5 cm, petiole length 2e6 cm, leaves have crenate margins and both sides glabrous covering base leaf (George and Joseph, 2009). Flower coloring is white to purple or pink with three to four flowers at each umbel. April to June are the flowering months, and plant fruits throughout the growth. Fruits attain the length of 2 in. in spherical or rectangular shape with intensely thickened pericarp (Shukla et al., 1999). Seed embryo is horizontally compressed and pendulous. Flowers are in fascicled umbels, each umbel consisting of three to four white to purple or pink flowers. C. asiatica is found abundantly in secondary succession communities, but it can grow wild under a varied range of climatic conditions. There is a variety of factors that affect germination of plants, including the condition of the plant, size, the temperature, and duration of exposure to light. The smaller and more succulent the plant, the greater the vulnerability is to death or damage from temperatures that are too low or too high.
2. CHEMISTRY C. asiatica is an aromatic plant that has a sweet taste and major pentacyclic triterpenoids including asiatic acid, brahmic acid, or madecassic acid, asiaticoside, and brahmoside. Other products include centelloside, centellose, and madecassoside (Schaneberg et al., 2003). The main chemical constituents of Indian pennywort are shown in Fig. 32.2.
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(A)
(B)
(D)
(C)
FIGURE 32.2 Main chemical constituents of Indian pennywort. (A) Asiaticoside. (B) Asiatic Acid. (C) Madecassoside. (D) Madecassic Acid.
A diverse range of biochemical compounds or secondary metabolites are present in C. asiatic, as witnessed by the scientific investigations. Due to the presence of biologically active components of triterpenes saponin, Centella plant plays a vital role in nutraceuticals and medicines (Plohmann et al., 1997). The triterpenes of Centella are made up of various compounds including asiaticoside (Fig. 32.2A), asiatic acid (Fig. 32.2B), brahmocide (Fig. 32.2C), madecassic acid (Fig. 32.2D), brahminoside, brahmic acid, centic acid, centelloside, centellic acid, thankiniside, and isothankunisode (Brinkhaus et al., 2000). Madecassic acid, madecassoside, asiatic acid, and asiaticoside are most important active triterpenes among them, biologically (Jayathirtha and Mishra, 2004). Moreover, it contains total phenolic contents (TPC) due to the presence of catechin, naringin, apigenin, rutin, quercetin, kaempferol, and volatile oils like farnesol and caryophyllene. Centella is also a rich source of vitamins A, B1, B2, and C, and niacin and carotene. The total ash contains iron, sodium, magnesium, calcium, phosphate, sulfate, and chloride (Zheng, 1989). A hundred grams of Centella contained 37 Kcal energy, 391 mg of potassium, 171 mg of calcium, and 2 g of protein (Thomas et al., 2010). Based on its large medicinal uses, many phytochemical studies have been carried out on C. asiatica. Terpenoids, asiaticoside, and glucosides separated from plant were more active in treatment of leprosy. The
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primary chemical description of terpenoids fraction comprises the prime biologic active components (Tholon et al., 2002). The chemical composition of Centella plant plays a very important role in medicinal and nutraceutical applications, due to biologically active components of triterpenes saponins (Biradar and Rachetti, 2013). The presence of high concentrations of phytochemicals is found in leaves, compared to the petiole and roots. The most important biologically active compounds are madecassic acid, madecassosides, asiatic acid, and asiaticoside among these phytochemicals. These phytochemicals are the biomarkers for the quality of C. asiatica. Phytochemicals are found in higher concentrations in the leaves relative to the roots and petioles. Among these phytochemicals, triterpenes, the most significant biologically active compounds are the asiatic acid, madecassic acid, asiaticoside, and madecassoside. They have been used as the biomarker components for quality assessment of Centella (James et al., 2008). Moreover, it contains TPC due to the presence of catechin, naringin, apigenin, rutin, quercetin, kaempferol, and volatile oils like farnesol and caryophyllene (Thomas et al., 2010). Out of 15 different variants of Centella, found in Malaysia, there are only three recognized triterpenes (madecassoside, asiaticoside, and asiatic acid). The concentration of these triterpenes varies with conditions and environment in which it grows (James and Dubery, 2009).
3. POSTHARVEST Leaves of gotu kola can be picked during the summer months. The best harvesting time is the morning, because at higher temperatures, the essential oil content decreases due to evaporation, as essential oils have some very volatile compounds in their composition. Flowers are harvested in months of April to June. The fresh leaves have flavor complexity, and aroma is lost in dried leaves due to evaporation of volatiles. On drying, flowers and leaves should not be broken; otherwise, flavor will be reduced due to loss of essential oil.
4. PROCESSING Gotu kola (C. asiatica), like other herbs, is used in different ways for a variety of purposes. Its fresh leaves are used as a salad. In addition, dry leaves, powdered leaves, and essential oil are processed. Chopped leaves and the entire plant can be stored frozen in the dark with or without oil. It is dried in a dry medium or shade, to prevent oxidation or evaporation of essential oil. To avoid the loss of volatile compounds, the drying temperature should not exceed 40 C. The essential oil extracted from flowers is of good quality, and oil extracted from leaves is of poor quality. Hydro
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distillation process is used for extraction of essential oil from freshly harvested herb plant leaves (Kumar and Gupta, 2002).
5. VALUE ADDITION The plant’s young leaves can be used both as a salad and sandwiches for its spicy flavor and as a cooked food. It is also used in curries, soups, stir fries, and as a taste enhancer with fish and vegetables. Leaves are used in a decoction of milk and infusions in dried or fresh form. Gotu kola is utilized in Sri Lankan cuisine (Sastravaha et al., 2005). Centella is supposed to be a nutritious plant. Malluma contains coconut and gotu kola along with chili powder, turmeric powder, lemon juice, and crushed green chilis (Babu et al., 1995). In Sri Lanka, a nutritious rich porridge called kola kenda is used by the people. This porridge is prepared with boiled red rice fluid, crushed gotu kola, and coconut milk. Pennywort, a sweet drink, uses Centella leaves. Leaves are also used in Thailand and Vietnam as a salad and in drinks (Wang et al., 2003).
6. USES C. asiatica is known as a common medicinal plant in different medicinal systems. In the Indian system of medicine called Ayurveda, it is used in compound formulations for curing gastrointestinal disorders and the diseases of the central nervous system and skin (Sharma and Kumar, 1998). It is one of the ingredients of the Indian summer drink thandaayyee. In Bangladesh, mashed Centella is eaten with rice. Dried leaves of Centella are used in tea and are recommended at a 0.33e0.68 g dosage three times a day. There is no evidence found for its side effects when staying within recommended limits. In oral application, asiaticoside 1 g/kg body weight has good tolerance and is nontoxic. It has a sweet aroma, so it is used in cosmetics (Pragada et al., 2004). Many investigators have described different biologic actions of C. asiatica. These activities are wound healing, antidepressant, antiaging, anticancer, etc. Madecassol, an extract of the plant having the constituents of asiatic acid, madecassic acid, and asiaticoside accelerates healing of grafted wounds by promoting fibroblast proliferation and extracellular matrix synthesis (Pandey et al., 1993).
7. PHARMACOLOGICAL USES 7.1 Antitumor Activity Crude extract of C. asiatica, orally administered in mice, and its partly purified fractions produced apoptosis in solid tumors and improved the
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life span of these tumor-bearing mice. Asiatic acid has anticancer activity against skin cancer (Gupta et al., 2003).
7.2 Memory Enhancing Effects An aqueous extract of this herb had major effects on enhancing memory and learning and reduced the levels of 5-hydroxytryptamine, dopamine, and norepinephrine. It also decreased the metabolites of these chemicals of neurotransmitter in brain (Nalini et al., 1992). C. asiatica is composed of brahmoside, isobrahmic acid, brahmic acid, and brahminoside, which has anticonvulsant, psychotropic, and sedative properties. It is beneficial in anxiety, dementia, and mental disorders too. Thus, in mental construction, the entire herb in a synergistic way produces the enhancement of attention, memory, and awareness in children who have a learning disability (Saha et al., 2002).
7.3 Cardioprotective Effects The alcoholic extract of the entire plant exhibited strong cardioprotective action in controlling ischemia reperfusioneinduced myocardial infraction in rats (Pragada et al., 2004).
7.4 Immunostimulating Effects Immunomodulating pectin extracted from C. asiatica possesses triterpenoids saponins and methanol extracts that have initial immunomodulatory influence. Alcoholic extract of the whole plant exhibited antiprotozoal lactenin contradiction of Entamoeba histolytica (Dhar et al., 1968).
7.5 Mental Retardation Effects Mentally retarded children who were orally given tablets of C. asiatica showed a substantial growth in behavior patterns and general ability (Dhanasekaran et al., 2009).
7.6 Antitubercular and Antileprotic Activity In the treatment of different kinds of tuberculosis and leprosy, asiaticoside is very useful (Rao et al., 2005). Clinical trials performed on normal adult mice exposed that the drug improved the level of serum cholesterol, red blood cells, total protein, blood sugar, and blood urea. It maintains the central nervous system and has a soothing effect on the body (Appa Rao et al., 1967).
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7.7 Wound Healing Effects Asiaticoside in C. asiatica has wound curative ability by increasing angiogenesis and collagen formation. The asiaticoside enhances the stretching strength of the newly formed skin and promotes the wound’s healing. It also prevents the inflammatory process, which may increase the capillary permeability and provoke hypertrophy in abrasions (Incandela et al., 2001). In the laboratory, antioxidant levels were observed on one animal to study the effects of asiaticoside, and the antioxidants played a key role in the healing of injuries (Shukla et al., 1999). The investigator studied the effects of asiaticoside on delayed as well as normal wound healing. In studies, it was observed that topical uses of 0.2% solution of asiaticoside resulted in an increase in collagen content, 57% in tensile strength, 56% in hydroxyproline, and well epithelization in guinea pig punch wounds. But healing is delayed in streptozotocin diabetic rats, so topical application of 0.4% solution of asiaticoside on punch injuries increased tensile strength, epithelization, hydroxyproline, and collagen contents there by smoothing the healing. Oral and topical administration of an alcoholic extract of C. asiatica was studied in the laboratory. Asiaticoside was more active orally at a 1 mg/kg dose in the guinea pig punch and 40 mg/disk in chick wound. The wounds treated by extract were observed to epithelialize quicker and the speed of wound contraction was greater, as compared to the control. These results showed that C. asiatica produced different actions on the different stages of scar repair in normal as well as delayed healing models (Shukla et al., 1999).
7.8 Effects on Venous Insufficiency It was postulated that C. asiatica helps in connective tissue maintenance by strengthening the weakened veins. In the cure of scleroderma, it can also assist in soothing connective tissue development, decreasing its formation by stimulating the formation of chondroitin sulfate and hyaluronidase. C. asiatica acts on the vascular wall of the connective tissues, being active in venous insufficiency and hypertensive microangiopathy. It also reduces the rate of capillary filtration by refining microcirculatory parameters (Cesarone et al., 1992).
7.9 Sedative and Anxiolytic Properties The effect of C. asiatica on the central nervous system was studied in the Indian literature for sedative, rejuvenant, stimulatory-nervine tonic, and intelligence- and tranquilizer-enhancing properties (Kumar and Gupta, 2002). It has been used conventionally as a sedative mediator in many Eastern cultures; the effect is primarily due to the brahminoside and
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brahmoside components. The anxiolytic activity is due to binding to cholecystokinin receptors, a group of gastrin protein joined receptors that fix the gastrin or the peptide hormones cholecystokinin. These receptors play a vital role in modulation of hunger, nociception, anxiety, and memory in humans and animals (Sairam et al., 2001).
7.10 Antidepressant Properties The antidepressant activities of entire triterpenes from C. asiatica on the immobility periods in forced swimming mice and amount of amino acid in brain tissue of mice was detected (Chen et al., 2005; Gohil et al., 2010; Young and Jewell, 1996).
7.11 Antiepileptic Properties Asian C. asiatica raises the cerebral levels of gamma aminobutyric acid, which is traditionally used as an anticonvulsant and anxiolytic. The steroids extracted from the plant are used for the treatment of leprosy. It also reduces the formation of spontaneous motor activity, lipid per oxidation products, hypothermia, potentiation in diazepam withdrawal-induced hyperactivity, and potentiation of pentobarbitone resting instant. The extract (200 mg/kg body weight) totally blocks pentylenetetrazolinduced convulsions. These conclusions suggest its probability as a central nervous system depressant, as well as antioxidant and anticonvulsant actions (Gnanapragasam et al., 2004).
7.12 Cognitive and Antioxidant Properties C. asiatica is recognized to increase the nervous system, brain, attention span, concentration, and to combat aging (Brinkhaus et al., 2000). An investigation showed Centella has cognitive-enhancing and antioxidant properties in normal rats. Aqueous extracts of C. asiatica (300, 200, and 100 mg/kg for 21 days) were analyzed for their effect in intracerebroventricular, oxidative stress and streptozotocin-induced cognitive injury in rats (Kumar and Gupta, 2002). The rats cured with C. asiatica had a dose-dependent rise in plus-maze paradigms, cognitive behavior, and passive avoidance. To give more information about the mechanism of this neuroprotection by C. asiatica, one study described that the phosphorylation of cyclic adenosine mono phosphate (AMP) response constituent binding protein was increased in both a neuroblastoma cell line showing amyloid beta and embryonic cortical prime cell culture in rats (Xu et al., 2008). Furthermore, the involvement of two major constituents to the enhanced phosphorylation was studied. In one more study, oral treatment
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with 50 mg/kg/day of rough methanol extract of C. asiatica for 14 days meaningfully improved the antioxidant enzymes, like catalase, superoxide dismutase, and glutathione peroxidase in lymphoma-bearing mice. The antioxidants like ascorbic acid and glutathione were reduced in the animals. Derivatives of asiatic acid exert the main neuroprotective effects on cultured cortical cells by defense mechanism. Therefore, these components were proved to be effective in defending neurons from the oxidative harm produced by exposure to excess glutamate (Lee et al., 1999).
7.13 Effects on Gastric Ulcer C. asiatica aqueous extract was found effective in curing gastric injuries caused by ethanol intake (Cheng and Koo, 2000). It also strengthened the gastric mucosal barrier and reduced free radical harmful effects. Animal studies in rats showed antiulcer prevention induced by cold and resistant stress. This property was associated with famotidine and sodium valproate. The reduction in gastric ulceration depends on the dose of herb extract or drug (Chatterjee et al., 1992). It was suggested that C. asiatica extract increased gamma-aminobutyric acid levels in the brain and made rats resistant to cold restraint ulceration (Zivkovic et al., 1982). In another study, C. asiatic fresh juice was tested in rats for its antiulcer activity against ethanol, cold restraint stress, aspirin, and pyrrolic ligatione induced gastric ulcer. The oral dose of 200 and 600 mg/kg twice a day for 5 days showed substantial protection against said experimental ulcer models, and results were comparable with those elicited by sucralfate. C. asiatica extracts showed little or no effect on offensive acid pepsin secretion. However, at 600 mg/kg, it significantly increased gastric juice mucin secretion and increased the mucosal cell glycoproteins, signifying an increase in cellular mucus (Sairam et al., 2001). One study presented that C. asiatica and its elements, asiaticosides, have an antiinflammatory property that carried out inhibition of nitric oxide and consequently assisted ulcer healing (Guo et al., 2004). Some other investigators also displayed the efficiency of C. asiatica by clinical and preclinical studies for curing gastric ulcers (Chen et al., 2005). C. asiatica has also been examined to prove its part in periodontal therapy (Sastravaha et al., 2005).
7.14 Antinociceptive and Antiinflammatory Properties The effects of C. asiatica upon inflammation and pain in rodent models were described. The antinociceptive action of the aqueous C. asiatica extract (300, 100, 30, and 10 mg/kg) was determined by means of acetic acideinduced hot plate and writhing technique in mice, while the
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antiinflammatory activity of C. asiatica was calculated through prostaglandin E2-induced foot edema in rats (Somchit et al., 2004). The aqueous C. asiatica extract exposed important antinociceptive activity with both the models analogous to aspirin but is less effective than morphine and has more antiinflammatory activity similar to mefenamic acid (Bateman et al., 1998). Currently, antirheumatic arthritis influence of madecassoside in type II collagen-induced arthritis (CIA) in mice was conducted to examine the healing potential and mechanisms of madecassoside on CIA. Madecassoside dose (40, 20, and 10 mg/kg), orally directed from the day of the antigen test for 20 consecutive days, reduced strictness of the disease on mice (Liu et al., 2008).
7.15 Radioprotection Effects It was proposed that C. asiatica might be valuable in inhibiting radiation-induced behavioral variations during clinical radiotherapy. The plant extracts were also used as a radioprotective at a sublethal dose of Co 60 gamma radiation (Sharma and Sharma, 2002). At 100 mg/kg dose, the survival period of the mice was significantly enlarged. Reduction in body weight of drug-treated group animals was significantly smaller in comparison with the animals that were only given radiation (Shobi and Goel, 2001).
7.16 Antidiabetic Activity To check the antidiabetic effects of C. asiatic, methanolic and ethanolic extracts were prepared, and their antidiabetic action on the alloxaninduced diabetic rats was checked. Alcoholic extracts significantly reduced the blood glucose level (Emran et al., 2015).
8. SIDE EFFECTS AND TOXICITY Indian pennywort is safe for pregnant women when applied on the skin. People suffering from liver diseases should not use Indian pennywort, as it enhances liver damage. Also, stop using this plant 2 weeks before surgery.
References Appa Rao, M., Usha, S., Rajagopalan, S., Sarangan, R., 1967. Six Months Results of a Double Blind Trial to Study the Effect of Mandookaparni and Punarnava on Normal Adults. Babu, T., Kuttan, G., Padikkala, J., 1995. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) urban. Journal of Ethnopharmacology 48, 53e57.
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Bateman, J., Chapman, R., Simpson, D., 1998. Possible toxicity of herbal remedies. Scottish Medical Journal 43, 7e15. Biradar, S.R., Rachetti, B.D., 2013. Extraction of some secondary metabolites & thin layer chromatography from different parts of Centella asiatica L.(URB). American Journal of Life Sciences 1, 243e247. Bown, D., 1995. Encyclopedia of Herbs and Their Uses, vol. 165. Dorling Kindersley Limited, New York, p. 289. Brinkhaus, B., Lindner, M., Schuppan, D., Hahn, E., 2000. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella aslatica. Phytomedicine 7, 427e448. Cesarone, M., Laurora, G., De Sanctis, M., Belcaro, G., 1992. Activity of Centella asiatica in venous insufficiency. Minerva Cardioangiologica 40, 137e143. Chatterjee, T., Chakraborty, A., Pathak, M., Sengupta, G., 1992. Effects of plant extract Centella asiatica (Linn.) on cold restraint stress ulcer in rats. Indian Journal of Experimental Biology 30, 889e891. Chen, Y., Han, T., Rui, Y., Yin, M., Qin, L., Zheng, H., 2005. Effects of total triterpenes of Centella asiatica on the corticosterone levels in serum and contents of monoamine in depression rat brain. Zhong Yao Cai¼ Zhongyaocai¼ Journal of Chinese Medicinal Materials 28, 492e496. Cheng, C., Koo, M., 2000. Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats. Life Sciences 67, 2647e2653. Devkota, A., Jha, P.K., 2009. Variation in growth of Centella asiatica along different soil composition. Botany Research International 2, 55e60. Dhanasekaran, M., Holcomb, L.A., Hitt, A.R., Tharakan, B., Porter, J.W., Young, K.A., Manyam, B.V., 2009. Centella asiatica extract selectively decreases amyloid b levels in hippocampus of Alzheimer’s disease animal model. Phytotherapy Research 23, 14e19. Dhar, M., Dhar, M., Dhawan, B., Mehrotra, B., Ray, C., 1968. Screening of Indian plants for biological activity: Part I. Indian Journal of Experimental Biology 6, 232e247. Duggina, P., Kalla, C.M., Varikasuvu, S.R., Bukke, S., Tartte, V., 2015. Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action. Journal of Physiology and Biochemistry 71, 435e454. Emran, T.B., Dutta, M., Uddin, M.M.N., Nath, A.K., Uddin, M.Z., 2015. Antidiabetic potential of the leaf extract of Centella asiatica in alloxaninduced diabetic rats. Jahangirnagar University Journal of Biological Sciences 4 (1), 51e59. George, M., Joseph, L., 2009. Anti-allergic, anti-pruritic, and anti-inflammatory activities of Centella asiatica extracts. African Journal of Traditional, Complementary and Alternative Medicines 6. Gnanapragasam, A., Ebenezar, K.K., Sathish, V., Govindaraju, P., Devaki, T., 2004. Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats. Life Sciences 76, 585e597. Goh, S.H., Chuah, C., Mok, J., Soepadmo, E., 1995. Malaysian Medicinal Plants for the Treatment of Cardiovascular Diseases. Petaling Jaya: Pelanduk Publications, ISBN 1089850565, 162pp. Gohil, K.J., Patel, J.A., Gajjar, A.K., 2010. Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian Journal of Pharmaceutical Sciences 72, 546. Guo, J.S., Cheng, C.L., Koo, M.W., 2004. Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats. Planta Medica 70, 1150e1154. Gupta, Y., Kumar, M.V., Srivastava, A., 2003. Effect of Centella asiatica on pentylenetetrazoleinduced kindling, cognition and oxidative stress in rats. Pharmacology Biochemistry and Behavior 74, 579e585.
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Hamid, A.A., Shah, Z.M., Muse, R., Mohamed, S., 2002. Characterisation of antioxidative activities of various extracts of Centella asiatica (L) urban. Food Chemistry 77, 465e469. Incandela, L., Cesarone, M., Cacchio, M., De Sanctis, M., 2001. Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy. Angiology 52, S9. James, J.T., Dubery, I.A., 2009. Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) urban. Molecules 14, 3922e3941. James, J.T., Meyer, R., Dubery, I.A., 2008. Characterisation of two phenotypes of Centella asiatica in Southern Africa through the composition of four triterpenoids in callus, cell suspensions and leaves. Plant Cell Tissue and Organ Culture 94, 91e99. Jamil, S.S., Nizami, Q., Salam, M., 2007. Centella asiatica (Linn.) urban: a review. Natural Product Radiance 6, 158e170. Jayathirtha, M., Mishra, S., 2004. Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica. Phytomedicine 11, 361e365. Kumar, M.V., Gupta, Y., 2002. Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats. Journal of Ethnopharmacology 79, 253e260. Larsen, H.O., Olsen, C.S., 2007. Unsustainable collection and unfair trade? Uncovering and assessing assumptions regarding Central Himalayan medicinal plant conservation. In: Plant Conservation and Biodiversity. Springer, pp. 105e123. Lee, M.K., Kim, S.R., Sung, S.H., Lim, D., Kim, H., Choi, H., Park, H.K., Je, S., Ki, Y., 1999. Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Research Communications in Molecular Pathology and Pharmacology 108, 75e86. Liu, M., Dai, Y., Yao, X., Li, Y., Luo, Y., Xia, Y., Gong, Z., 2008. Anti-rheumatoid arthritic effect of madecassoside on type II collagen-induced arthritis in mice. International Immunopharmacology 8, 1561e1566. Nalini, K., Aroor, A., Rao, A., Karanth, K., 1992. Effect of Centella asiatica fresh leaf aqueous extract on learning and memory and biogenic amine turnover in albino rats. Fitoterapia 63, 231e238. Pandey, N., Tewari, K., Tewari, R., Joshi, G., Pande, V., Pandey, G., 1993. Medicinal plants of Kumaon Himalaya: strategies for conservation. Himalayan Biodiversity Conservation Strategies 3, 293e302. Plohmann, B., Bader, G., Hiller, K., Franz, G., 1997. Immunomodulatory and antitumoral effects of triterpenoid saponins. Die Pharmazie 52, 953e957. Pragada, R., Veeravalli, K., Chowdary, K., Routhu, K., 2004. Cardioprotective activity of Hydrocotyle asiatica L. in ischemia-reperfusion induced myocardial infarction in rats. Journal of Ethnopharmacology 93, 105e108. Rao, S.B., Chetana, M., Devi, P.U., 2005. Centella asiatica treatment during postnatal period enhances learning and memory in mice. Physiology & Behavior 86, 449e457. Saha, A., Bhatia, B., Kulkarni, K.S., 2002. Evaluation of the Efficacy of Mentat in Children with Learning Disability: A Placebo-Controlled Double-Blind Clinical Trial. Sairam, K., Rao, C.V., Goel, R., 2001. Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats. Indian Journal of Experimental Biology 39, 137e142. Sastravaha, G., Gassmann, G., Sangtherapitikul, P., Grimm, W.-D., 2005. Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts in supportive periodontal therapy. Journal of the International Academy of Periodontology 7, 70e79. Schaneberg, B., Mikell, J., Bedir, E., Khan, I., Nachname, V., 2003. An improved HPLC method for quantitative determination of six triterpenes in Centella asiatica extracts and commercial products. Die PharmazieeAn International Journal of Pharmaceutical Sciences 58, 381e384.
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Sharma, B., Kumar, A., 1998. Biodiversity of medicinal plants of Triyugi Narain (Garhwal Himalaya) and their conservation. In: National Conference on Recent Trends in Spices and Medicinal Plant Research, Calcutta, WB, India, p. 78. Sharma, J., Sharma, R., 2002. Radioprotection of Swiss albino mouse by Centella asiatica extract. Phytotherapy Research 16, 785e786. Shobi, V., Goel, H., 2001. Protection against radiation-induced conditioned taste aversion by Centella asiatica. Physiology & Behavior 73, 19e23. Shukla, A., Rasik, A., Jain, G., Shankar, R., Kulshrestha, D., Dhawan, B., 1999. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. Journal of Ethnopharmacology 65, 1e11. Somchit, M., Sulaiman, M., Zuraini, A., Samsuddin, L., Somchit, N., Israf, D., Moin, S., 2004. Antinociceptive and antiinflammatory effects of Centella asiatica. Indian Journal of Pharmacology 36, 377. Tholon, L., Neliat, G., Chesne, C., Saboureau, D., Perrier, E., Branka, J.-E., 2002. An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of slimming liposomes: An unexpected a2 -adrenergic antagonism. Journal of Cosmetic Science 53, 209e218. Thomas, M.T., Kurup, R., Johnson, A.J., Chandrika, S.P., Mathew, P.J., Dan, M., Baby, S., 2010. Elite genotypes/chemotypes, with high contents of madecassoside and asiaticoside, from sixty accessions of Centella asiatica of south India and the Andaman Islands: for cultivation and utility in cosmetic and herbal drug applications. Industrial Crops and Products 32, 545e550. Wang, X.-S., Dong, Q., Zuo, J.-P., Fang, J.-N., 2003. Structure and potential immunological activity of a pectin from Centella asiatica (L.) urban. Carbohydrate Research 338, 2393e2402. Xu, Y., Cao, Z., Khan, I., Luo, Y., 2008. Gotu Kola (Centella asiatica) extract enhances phosphorylation of cyclic AMP response element binding protein in neuroblastoma cells expressing amyloid beta peptide. Journal of Alzheimer’s Disease: JAD 13, 341e349. Young, G., Jewell, D., 1996. Creams for Preventing Stretch Marks in Pregnancy. The Cochrane Library. Zheng, M., 1989. An experimental study of the anti-HSV-II action of 500 herbal drugs. Journal of Traditional Chinese Medicine 9, 113. Zivkovic, B., Scatton, B., Dedek, J., Bartholini, G., 1982. GABA influence on noradrenergic and serotonergic transmissions: implications in mood regulation. In: New Vistas in Depression, vol. 40. Pergamon Press, Oxford, pp. 195e201.
32 Indian Pennywort Shahzia Yousaf1, Muhammad Asif Hanif1, Rafia Rehman1, Muhammad Waqar Azeem1, Anca Racoti2 1
Department of Chemistry, University of Agriculture, Faisalabad, Pakistan; 2 The National Institute for Research & Development in Chemistry and Petrochemistry e ICECHIM, Bucharest, Romania
O U T L I N E 1. Botany 1.1 Introduction 1.2 History/Origin 1.3 Location/Demography 1.4 Botany, Morphology, Ecology
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1. BOTANY 1.1 Introduction Indian pennywort (Centella asiatica) (Fig. 32.1) is a perennial, clonal, herbaceous plant belonging to Umbelliferae (Apiaceae) family that is found all over India, growing in damp areas up to an altitude of 1800 m. It occurs commonly in subtropical and tropical countries, including parts of Pakistan, India, Madagascar, Sri Lanka, Eastern Europe, South Africa, and
FIGURE 32.1
Dried Indian pennywort.
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the South Pacific. Twenty species that are closely resembled to C. asiatica propagate in most parts of the tropic or wet pantropical parts like rice paddies, also in rocky places and higher altitudes (Bown, 1995). It is a tasteless, weakly scented plant that more frequently flourishes in waterrich places. Its leaves are green, small, fan-shaped with white or light pink to purple flowers, and it has small, elliptical fruit. For medicinal purposes the entire plant is used. It is mostly used for blood purification as well as treating memory improvement (intellect), high blood pressure, and other similar problems. In Ayurveda, C. asiatica is one of the main herbs for activating the nerves and brain cells. To treat emotional disorders, such as depression, hakims use C. asiatica. In Western medicine, in the mid-20th century, C. asiatica and its alcohol extracts were used in the treatment of leprosy (Duggina et al., 2015). C. asiatica was confused earlier with Bacopa monnieri in the Indian market because both were sold by the “Brahmi” name. Later on, the problem was solved by giving a separate name: brahmi for B. monnieri and mandookaparni for C. Asiatic. Due to extensive use at a large scale along with little cultivation, wild species of the plant are disappearing from sight, and attempts have not been made for its revival (Larsen and Olsen, 2007). Due to the same reason, International Union for Conservation of Nature and Natural Resources enlisted it as a rare and threatened plant species. Region-wise common names are gotu kola in Urdu and thankuni in Bengali, mandookparni in Hindi, pegaga in Malay, bekaparanamu in Telgu, vallarai in Tamil, and kodagam in Malayalam.
1.2 History/Origin C. asiatica (Linn), native to Sri Lanka, South Africa, Madagascar, and Malaysia, has been used since ancient times by tribal groups and cultures as a medicinal herb. For about 2000 years, C. asiatic has been a part of Chinese herbal medicines and 3000 years in Indian Ayurvedic system of medicines (Gnanapragasam et al., 2004). In Ayurvedic medicines, mandukaparni is used for the treatment of skin diseases, leprosy, gastric catarrh, elephantiasis, kidney troubles, asthma, bronchitis, and leucorrhoea, while in Chinese herbal medicine, it is used for curing toxic fever and leucorrhoea. In Malaysia, C. Asiatic is used to cure anxiety, eczema, and mental fatigue. It is also eaten as salad when fresh (Goh et al., 1995). Fresh plant extracts have been used for many years by the people of Malay Peninsula and Java for healing wounds, internally and externally. The plant extracts are also an active part of brain tonics for mental impairment. The presence of pentacyclic triterpenes, madecassoside, madecassic acid, asiaticoside, and asiatic acid is responsible for these properties (Jamil et al., 2007).
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1.3 Location/Demography C. asiatic grows all over the tropical and subtropical areas of India up to 600 m altitude. It is also found at an altitude of 1200 m in Mount Abu (Rajasthan, India) and at even more altitude of 1550 m in Sikkim (northeastern Indian state). Sandy loam (60%) type of soil proved to be the utmost choice for regeneration of it, rather than clayey soil (Devkota and Jha, 2009). In the wild, Centella plant is found in wet or moist soils of marshes, swamp, bogs, and along the margins of ponds, lakes, irrigation, streams, and drainage canals of irrigated paddy fields. It is also found in wet pine savannas, flat woods, and palmetto flats, often forming meadows. It grows in water or on land (Hamid et al., 2002). The species is pantropic, found in the United States from Delaware to southern Florida, in West Indies, Mexico, central and southern America, Australia, Sri Lanka, and the Philippines.
1.4 Botany, Morphology, Ecology C. asiatic (L.) is a flat, creeping, stoloniferous, perennial herb, faintly aromatic that grows up to 15 cm height. Stem is glabrous, striated, rooting at nodes. Each node has one to three leaves with a width of 1.5e5 cm, petiole length 2e6 cm, leaves have crenate margins and both sides glabrous covering base leaf (George and Joseph, 2009). Flower coloring is white to purple or pink with three to four flowers at each umbel. April to June are the flowering months, and plant fruits throughout the growth. Fruits attain the length of 2 in. in spherical or rectangular shape with intensely thickened pericarp (Shukla et al., 1999). Seed embryo is horizontally compressed and pendulous. Flowers are in fascicled umbels, each umbel consisting of three to four white to purple or pink flowers. C. asiatica is found abundantly in secondary succession communities, but it can grow wild under a varied range of climatic conditions. There is a variety of factors that affect germination of plants, including the condition of the plant, size, the temperature, and duration of exposure to light. The smaller and more succulent the plant, the greater the vulnerability is to death or damage from temperatures that are too low or too high.
2. CHEMISTRY C. asiatica is an aromatic plant that has a sweet taste and major pentacyclic triterpenoids including asiatic acid, brahmic acid, or madecassic acid, asiaticoside, and brahmoside. Other products include centelloside, centellose, and madecassoside (Schaneberg et al., 2003). The main chemical constituents of Indian pennywort are shown in Fig. 32.2.
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(A)
(B)
(D)
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FIGURE 32.2 Main chemical constituents of Indian pennywort. (A) Asiaticoside. (B) Asiatic Acid. (C) Madecassoside. (D) Madecassic Acid.
A diverse range of biochemical compounds or secondary metabolites are present in C. asiatic, as witnessed by the scientific investigations. Due to the presence of biologically active components of triterpenes saponin, Centella plant plays a vital role in nutraceuticals and medicines (Plohmann et al., 1997). The triterpenes of Centella are made up of various compounds including asiaticoside (Fig. 32.2A), asiatic acid (Fig. 32.2B), brahmocide (Fig. 32.2C), madecassic acid (Fig. 32.2D), brahminoside, brahmic acid, centic acid, centelloside, centellic acid, thankiniside, and isothankunisode (Brinkhaus et al., 2000). Madecassic acid, madecassoside, asiatic acid, and asiaticoside are most important active triterpenes among them, biologically (Jayathirtha and Mishra, 2004). Moreover, it contains total phenolic contents (TPC) due to the presence of catechin, naringin, apigenin, rutin, quercetin, kaempferol, and volatile oils like farnesol and caryophyllene. Centella is also a rich source of vitamins A, B1, B2, and C, and niacin and carotene. The total ash contains iron, sodium, magnesium, calcium, phosphate, sulfate, and chloride (Zheng, 1989). A hundred grams of Centella contained 37 Kcal energy, 391 mg of potassium, 171 mg of calcium, and 2 g of protein (Thomas et al., 2010). Based on its large medicinal uses, many phytochemical studies have been carried out on C. asiatica. Terpenoids, asiaticoside, and glucosides separated from plant were more active in treatment of leprosy. The
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primary chemical description of terpenoids fraction comprises the prime biologic active components (Tholon et al., 2002). The chemical composition of Centella plant plays a very important role in medicinal and nutraceutical applications, due to biologically active components of triterpenes saponins (Biradar and Rachetti, 2013). The presence of high concentrations of phytochemicals is found in leaves, compared to the petiole and roots. The most important biologically active compounds are madecassic acid, madecassosides, asiatic acid, and asiaticoside among these phytochemicals. These phytochemicals are the biomarkers for the quality of C. asiatica. Phytochemicals are found in higher concentrations in the leaves relative to the roots and petioles. Among these phytochemicals, triterpenes, the most significant biologically active compounds are the asiatic acid, madecassic acid, asiaticoside, and madecassoside. They have been used as the biomarker components for quality assessment of Centella (James et al., 2008). Moreover, it contains TPC due to the presence of catechin, naringin, apigenin, rutin, quercetin, kaempferol, and volatile oils like farnesol and caryophyllene (Thomas et al., 2010). Out of 15 different variants of Centella, found in Malaysia, there are only three recognized triterpenes (madecassoside, asiaticoside, and asiatic acid). The concentration of these triterpenes varies with conditions and environment in which it grows (James and Dubery, 2009).
3. POSTHARVEST Leaves of gotu kola can be picked during the summer months. The best harvesting time is the morning, because at higher temperatures, the essential oil content decreases due to evaporation, as essential oils have some very volatile compounds in their composition. Flowers are harvested in months of April to June. The fresh leaves have flavor complexity, and aroma is lost in dried leaves due to evaporation of volatiles. On drying, flowers and leaves should not be broken; otherwise, flavor will be reduced due to loss of essential oil.
4. PROCESSING Gotu kola (C. asiatica), like other herbs, is used in different ways for a variety of purposes. Its fresh leaves are used as a salad. In addition, dry leaves, powdered leaves, and essential oil are processed. Chopped leaves and the entire plant can be stored frozen in the dark with or without oil. It is dried in a dry medium or shade, to prevent oxidation or evaporation of essential oil. To avoid the loss of volatile compounds, the drying temperature should not exceed 40 C. The essential oil extracted from flowers is of good quality, and oil extracted from leaves is of poor quality. Hydro
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distillation process is used for extraction of essential oil from freshly harvested herb plant leaves (Kumar and Gupta, 2002).
5. VALUE ADDITION The plant’s young leaves can be used both as a salad and sandwiches for its spicy flavor and as a cooked food. It is also used in curries, soups, stir fries, and as a taste enhancer with fish and vegetables. Leaves are used in a decoction of milk and infusions in dried or fresh form. Gotu kola is utilized in Sri Lankan cuisine (Sastravaha et al., 2005). Centella is supposed to be a nutritious plant. Malluma contains coconut and gotu kola along with chili powder, turmeric powder, lemon juice, and crushed green chilis (Babu et al., 1995). In Sri Lanka, a nutritious rich porridge called kola kenda is used by the people. This porridge is prepared with boiled red rice fluid, crushed gotu kola, and coconut milk. Pennywort, a sweet drink, uses Centella leaves. Leaves are also used in Thailand and Vietnam as a salad and in drinks (Wang et al., 2003).
6. USES C. asiatica is known as a common medicinal plant in different medicinal systems. In the Indian system of medicine called Ayurveda, it is used in compound formulations for curing gastrointestinal disorders and the diseases of the central nervous system and skin (Sharma and Kumar, 1998). It is one of the ingredients of the Indian summer drink thandaayyee. In Bangladesh, mashed Centella is eaten with rice. Dried leaves of Centella are used in tea and are recommended at a 0.33e0.68 g dosage three times a day. There is no evidence found for its side effects when staying within recommended limits. In oral application, asiaticoside 1 g/kg body weight has good tolerance and is nontoxic. It has a sweet aroma, so it is used in cosmetics (Pragada et al., 2004). Many investigators have described different biologic actions of C. asiatica. These activities are wound healing, antidepressant, antiaging, anticancer, etc. Madecassol, an extract of the plant having the constituents of asiatic acid, madecassic acid, and asiaticoside accelerates healing of grafted wounds by promoting fibroblast proliferation and extracellular matrix synthesis (Pandey et al., 1993).
7. PHARMACOLOGICAL USES 7.1 Antitumor Activity Crude extract of C. asiatica, orally administered in mice, and its partly purified fractions produced apoptosis in solid tumors and improved the
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life span of these tumor-bearing mice. Asiatic acid has anticancer activity against skin cancer (Gupta et al., 2003).
7.2 Memory Enhancing Effects An aqueous extract of this herb had major effects on enhancing memory and learning and reduced the levels of 5-hydroxytryptamine, dopamine, and norepinephrine. It also decreased the metabolites of these chemicals of neurotransmitter in brain (Nalini et al., 1992). C. asiatica is composed of brahmoside, isobrahmic acid, brahmic acid, and brahminoside, which has anticonvulsant, psychotropic, and sedative properties. It is beneficial in anxiety, dementia, and mental disorders too. Thus, in mental construction, the entire herb in a synergistic way produces the enhancement of attention, memory, and awareness in children who have a learning disability (Saha et al., 2002).
7.3 Cardioprotective Effects The alcoholic extract of the entire plant exhibited strong cardioprotective action in controlling ischemia reperfusioneinduced myocardial infraction in rats (Pragada et al., 2004).
7.4 Immunostimulating Effects Immunomodulating pectin extracted from C. asiatica possesses triterpenoids saponins and methanol extracts that have initial immunomodulatory influence. Alcoholic extract of the whole plant exhibited antiprotozoal lactenin contradiction of Entamoeba histolytica (Dhar et al., 1968).
7.5 Mental Retardation Effects Mentally retarded children who were orally given tablets of C. asiatica showed a substantial growth in behavior patterns and general ability (Dhanasekaran et al., 2009).
7.6 Antitubercular and Antileprotic Activity In the treatment of different kinds of tuberculosis and leprosy, asiaticoside is very useful (Rao et al., 2005). Clinical trials performed on normal adult mice exposed that the drug improved the level of serum cholesterol, red blood cells, total protein, blood sugar, and blood urea. It maintains the central nervous system and has a soothing effect on the body (Appa Rao et al., 1967).
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7.7 Wound Healing Effects Asiaticoside in C. asiatica has wound curative ability by increasing angiogenesis and collagen formation. The asiaticoside enhances the stretching strength of the newly formed skin and promotes the wound’s healing. It also prevents the inflammatory process, which may increase the capillary permeability and provoke hypertrophy in abrasions (Incandela et al., 2001). In the laboratory, antioxidant levels were observed on one animal to study the effects of asiaticoside, and the antioxidants played a key role in the healing of injuries (Shukla et al., 1999). The investigator studied the effects of asiaticoside on delayed as well as normal wound healing. In studies, it was observed that topical uses of 0.2% solution of asiaticoside resulted in an increase in collagen content, 57% in tensile strength, 56% in hydroxyproline, and well epithelization in guinea pig punch wounds. But healing is delayed in streptozotocin diabetic rats, so topical application of 0.4% solution of asiaticoside on punch injuries increased tensile strength, epithelization, hydroxyproline, and collagen contents there by smoothing the healing. Oral and topical administration of an alcoholic extract of C. asiatica was studied in the laboratory. Asiaticoside was more active orally at a 1 mg/kg dose in the guinea pig punch and 40 mg/disk in chick wound. The wounds treated by extract were observed to epithelialize quicker and the speed of wound contraction was greater, as compared to the control. These results showed that C. asiatica produced different actions on the different stages of scar repair in normal as well as delayed healing models (Shukla et al., 1999).
7.8 Effects on Venous Insufficiency It was postulated that C. asiatica helps in connective tissue maintenance by strengthening the weakened veins. In the cure of scleroderma, it can also assist in soothing connective tissue development, decreasing its formation by stimulating the formation of chondroitin sulfate and hyaluronidase. C. asiatica acts on the vascular wall of the connective tissues, being active in venous insufficiency and hypertensive microangiopathy. It also reduces the rate of capillary filtration by refining microcirculatory parameters (Cesarone et al., 1992).
7.9 Sedative and Anxiolytic Properties The effect of C. asiatica on the central nervous system was studied in the Indian literature for sedative, rejuvenant, stimulatory-nervine tonic, and intelligence- and tranquilizer-enhancing properties (Kumar and Gupta, 2002). It has been used conventionally as a sedative mediator in many Eastern cultures; the effect is primarily due to the brahminoside and
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brahmoside components. The anxiolytic activity is due to binding to cholecystokinin receptors, a group of gastrin protein joined receptors that fix the gastrin or the peptide hormones cholecystokinin. These receptors play a vital role in modulation of hunger, nociception, anxiety, and memory in humans and animals (Sairam et al., 2001).
7.10 Antidepressant Properties The antidepressant activities of entire triterpenes from C. asiatica on the immobility periods in forced swimming mice and amount of amino acid in brain tissue of mice was detected (Chen et al., 2005; Gohil et al., 2010; Young and Jewell, 1996).
7.11 Antiepileptic Properties Asian C. asiatica raises the cerebral levels of gamma aminobutyric acid, which is traditionally used as an anticonvulsant and anxiolytic. The steroids extracted from the plant are used for the treatment of leprosy. It also reduces the formation of spontaneous motor activity, lipid per oxidation products, hypothermia, potentiation in diazepam withdrawal-induced hyperactivity, and potentiation of pentobarbitone resting instant. The extract (200 mg/kg body weight) totally blocks pentylenetetrazolinduced convulsions. These conclusions suggest its probability as a central nervous system depressant, as well as antioxidant and anticonvulsant actions (Gnanapragasam et al., 2004).
7.12 Cognitive and Antioxidant Properties C. asiatica is recognized to increase the nervous system, brain, attention span, concentration, and to combat aging (Brinkhaus et al., 2000). An investigation showed Centella has cognitive-enhancing and antioxidant properties in normal rats. Aqueous extracts of C. asiatica (300, 200, and 100 mg/kg for 21 days) were analyzed for their effect in intracerebroventricular, oxidative stress and streptozotocin-induced cognitive injury in rats (Kumar and Gupta, 2002). The rats cured with C. asiatica had a dose-dependent rise in plus-maze paradigms, cognitive behavior, and passive avoidance. To give more information about the mechanism of this neuroprotection by C. asiatica, one study described that the phosphorylation of cyclic adenosine mono phosphate (AMP) response constituent binding protein was increased in both a neuroblastoma cell line showing amyloid beta and embryonic cortical prime cell culture in rats (Xu et al., 2008). Furthermore, the involvement of two major constituents to the enhanced phosphorylation was studied. In one more study, oral treatment
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with 50 mg/kg/day of rough methanol extract of C. asiatica for 14 days meaningfully improved the antioxidant enzymes, like catalase, superoxide dismutase, and glutathione peroxidase in lymphoma-bearing mice. The antioxidants like ascorbic acid and glutathione were reduced in the animals. Derivatives of asiatic acid exert the main neuroprotective effects on cultured cortical cells by defense mechanism. Therefore, these components were proved to be effective in defending neurons from the oxidative harm produced by exposure to excess glutamate (Lee et al., 1999).
7.13 Effects on Gastric Ulcer C. asiatica aqueous extract was found effective in curing gastric injuries caused by ethanol intake (Cheng and Koo, 2000). It also strengthened the gastric mucosal barrier and reduced free radical harmful effects. Animal studies in rats showed antiulcer prevention induced by cold and resistant stress. This property was associated with famotidine and sodium valproate. The reduction in gastric ulceration depends on the dose of herb extract or drug (Chatterjee et al., 1992). It was suggested that C. asiatica extract increased gamma-aminobutyric acid levels in the brain and made rats resistant to cold restraint ulceration (Zivkovic et al., 1982). In another study, C. asiatic fresh juice was tested in rats for its antiulcer activity against ethanol, cold restraint stress, aspirin, and pyrrolic ligatione induced gastric ulcer. The oral dose of 200 and 600 mg/kg twice a day for 5 days showed substantial protection against said experimental ulcer models, and results were comparable with those elicited by sucralfate. C. asiatica extracts showed little or no effect on offensive acid pepsin secretion. However, at 600 mg/kg, it significantly increased gastric juice mucin secretion and increased the mucosal cell glycoproteins, signifying an increase in cellular mucus (Sairam et al., 2001). One study presented that C. asiatica and its elements, asiaticosides, have an antiinflammatory property that carried out inhibition of nitric oxide and consequently assisted ulcer healing (Guo et al., 2004). Some other investigators also displayed the efficiency of C. asiatica by clinical and preclinical studies for curing gastric ulcers (Chen et al., 2005). C. asiatica has also been examined to prove its part in periodontal therapy (Sastravaha et al., 2005).
7.14 Antinociceptive and Antiinflammatory Properties The effects of C. asiatica upon inflammation and pain in rodent models were described. The antinociceptive action of the aqueous C. asiatica extract (300, 100, 30, and 10 mg/kg) was determined by means of acetic acideinduced hot plate and writhing technique in mice, while the
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antiinflammatory activity of C. asiatica was calculated through prostaglandin E2-induced foot edema in rats (Somchit et al., 2004). The aqueous C. asiatica extract exposed important antinociceptive activity with both the models analogous to aspirin but is less effective than morphine and has more antiinflammatory activity similar to mefenamic acid (Bateman et al., 1998). Currently, antirheumatic arthritis influence of madecassoside in type II collagen-induced arthritis (CIA) in mice was conducted to examine the healing potential and mechanisms of madecassoside on CIA. Madecassoside dose (40, 20, and 10 mg/kg), orally directed from the day of the antigen test for 20 consecutive days, reduced strictness of the disease on mice (Liu et al., 2008).
7.15 Radioprotection Effects It was proposed that C. asiatica might be valuable in inhibiting radiation-induced behavioral variations during clinical radiotherapy. The plant extracts were also used as a radioprotective at a sublethal dose of Co 60 gamma radiation (Sharma and Sharma, 2002). At 100 mg/kg dose, the survival period of the mice was significantly enlarged. Reduction in body weight of drug-treated group animals was significantly smaller in comparison with the animals that were only given radiation (Shobi and Goel, 2001).
7.16 Antidiabetic Activity To check the antidiabetic effects of C. asiatic, methanolic and ethanolic extracts were prepared, and their antidiabetic action on the alloxaninduced diabetic rats was checked. Alcoholic extracts significantly reduced the blood glucose level (Emran et al., 2015).
8. SIDE EFFECTS AND TOXICITY Indian pennywort is safe for pregnant women when applied on the skin. People suffering from liver diseases should not use Indian pennywort, as it enhances liver damage. Also, stop using this plant 2 weeks before surgery.
References Appa Rao, M., Usha, S., Rajagopalan, S., Sarangan, R., 1967. Six Months Results of a Double Blind Trial to Study the Effect of Mandookaparni and Punarnava on Normal Adults. Babu, T., Kuttan, G., Padikkala, J., 1995. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) urban. Journal of Ethnopharmacology 48, 53e57.
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