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Current updates on Centella asiatica: Phytochemistry, pharmacology and


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Medicinal Plant Research 2013, Vol.3, No.4, 20-36
http://mpr.sophiapublisher.com

Review Open Access


Current Updates on Centella asiatica: Phytochemistry, Pharmacology and
Traditional Uses
Dipankar Chandra Roy , Shital Kumar Barman , Md. Munan Shaik
Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia-7003, Bangladesh
Corresponding author email: munanbt2004@gmail.com; mmshaik@btge.iu.ac.bd; Authors
Medicinal Plant Research, 2013, Vol.3, No.4 doi: 10.5376/mpr.2013.03.0004
Received: 14 Jan., 2013
Accepted: 23 Jan., 2013
Published: 28 Jan., 2013
Copyright © 2012 Dipankar et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:
Dipankar C.R., et al., 2013, Current Updates on Centella asiatica: Phytochemistry, Pharmacology and Traditional Uses, Medicinal Plant Research, Vol.3, No.4
20-36 (doi: 10.5376/mpr.2013.03.0004)

Abstract Plants have been demonstrated extraordinary source of medicine, and recently focus on medicinal plant research has
increased. Centella asiatica is well known for its traditional uses and medicinal properties for the treatment of many diseases. The
published literatures mention the use of this plant as whole and bioactive compounds isolated are widely used in the treatment of
various human ailments. C. asiatica reported to possess various pharmacological activities: antimicrobial activity, anticancer activity,
wound healing activity, neuroprotechtive activity, immunomodulatory activity, anti-inflammatory activity, hepatoprotective activity,
insecticidal activity, and antioxidant activity. C. asiatica is also rich in flavonoids and terpenoids compounds among them asiatic acid,
asiaticoside, madecassoside is well characterized for its pharmacological value. The present review summarized widespread
information on phytochemistry, isolated and characterized bioactive compounds, pharmacological properties, in vitro propagation and
traditional uses of the important medicinal plant C. asiatica.
Keywords Centella asiatica; Medicinal Plants; Triterpenes; Terpenoids phytochemistry; Pharmacology; Neuroprotechtive activity;
Wound healing actitivty; Anti-inflammatory activity; Anticancer activity

Background
Medicinal plants are an important episode in the internodes (Jamil et al., 2007; Koh et al., 2009).
medical sector. Around 5 000 species have specific Glabrous leaves, 1-3 arising from each node of the
therapeutic value among 250 000 higher plant species stems, are green, fan-shaped or round renifrom,
on earth (Joy et al., 1998). Centella asiatica has a long 1.4 cm by 1.7 cm with crenate or dentate margin
history in ancient Ayurvedic remedy, used in wound (Jamil et al., 2007; Koh et al., 2009). Flowers
healing, cleansing for skin problem and digestive occurring in July- September are umbels with 3-4
disorders (Chevallier, 2001) and effective in treatment white or light purple-to-pink petals bearing 4mm long
of stomach ulcers, mental fatigue, diarrhea, epilepsy, oval to globular shaped fruit (Chauhan, 1999; Jamil et
hepatitis, syphilis and asthma (Goldstein and al., 2007; Koh et al., 2009). The most used part for
Goldstein, 2012). Such traditional uses and reputation medicinal purposes is dried whole plant, leaves and
of this species cross over the boundary limit of stems. C. asiatica plant is indigenous to Bangladesh,
Bangladesh, India, and Srilanka and now extensively India, West Pakistan, China, Japan, America and the
used in the West (Chevallier, 2001; Meulenbeld and pacific (Koh et al., 2009). This plant is commonly
Wujastyk, 2001). C. asiatica and Hydrocotyle asiatica, seen in moist, sandy or clayey soils waste places
belongs to family Apiaceae (Umbelliferae) are used (Jamil et al., 2007).
synonymously and commonly known as Thankuni
(Bengali), Bemgsag/Brahma-Manduki/Gotukola/Khu- Phytochemistry
lakhudi/Mandookaparni (Hindi), Indian Pennywort/ C. asiatica is a rich source of amino acids, flavonoids,
Marsh Pennywort/ Gotu kola (English) (Singh et al., terpenoids, essential oils, alkaloids etc. (Table 1).
2010). C. asiatica is creeping, perennial herb with up Most of the phytochemical studies concentrated on
to 2m long slender and tender horizontal reddish leaves and the constituents vary depending upon the
prostrate stolons, characterized by long rooting geographical distribution (Chong and Aziz, 2011).

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Table 1 Chemical constituents of C. asiatica


Main groups Constituents References
Amino acids Alanine and serine (major components), aminobutyrate, aspartate, glutamate, (Barnes et al., 2007;
histidine, lysine, threonine, arginine, leucine, iso-leucine, valine, methionine, Chong NJ and Aziz,
tyrosine, phenylalanine, proline, cystine, glycine. 2011),
Carbohydrates Glucose, mesoinositol, centellose, pectin, arabinogalactan (Chong NJ and Aziz,
2011)
Phenols Flavonoids: Kaempferol, kaempferol-3-o-β-d-glucuronide, castilliferol, quercetin, (Bhandari et al., 2007;
quercetin-3-o-β-d-glucuronide, castillicetin, apigenin, rutin, luteolin, naringin Zheng and Qin, 2007;
Chong NJ and Aziz,
2011)
Phenylpropanoids: Rosmarinic acid, chlorogenic acid, 3,4-di-o-caffeoyl quinic acid, (Chong NJ and Aziz,
1,5-di-o-caffeoyl quinic acid, 3,5-di-o-caffeoyl quinic acid, 4,5-di-o-caffeoyl quinic 2011)
acid, isochlorogenic acid
Tannin: Tannin, phlobatannin (Chong NJ and Aziz,
2011)
Terpenoids Triterpenes, asiaticoside, centelloside, madecassoside, brahmoside, brahminoside (Barnes et al., 2007;
(saponin glycosides), asiaticentoic acid, centellic acid, centoic acid, madecassic Jamil et al., 2007)
acid, terminolic acid and betulic acid.
Volatile oils and Various terpenoids: β-caryophyllene, trans β-farnesene and germacrene D (Barnes et al., 2007;
fatty oils (sesquiterpenes), α-pinene and β-pinene. Jamil et al., 2007)
Fatty acids: linoleic acid, linolenic acid, lignocene, oleic acid, palmitic acid, stearic
acid.
Vitamins Ascorbic acid, nicotinic acid, β-carotene (Chong NJ and Aziz,
2011)
Mineral Calcium, phosphorus, iron, potassium, magnesium, manganese, zinc, sodium, (Chong NJ and Aziz,
copper 2011)
Other constituents Hydrocotylin (an alkaloid), vallerine (a bitter principle), phytosterols (e.g. (Barnes et al., 2007;
campesterol, sitosterol, stigmasterol), resin. ~14 different polyacetylenes Chong NJ and Aziz,
(8-acetoxycentellynol, cadiyenol, dotriacont-8-en-1-oic acid, 11-oxoheneicosanyl 2011)
cyclohexane).

Bioactive compounds equiseti CGMCC 3.3658, and Streptomyces griseus


C. asiatica is being used as a natural source of CGMCC 4.18 strains was investigated and structure
medicine for long time. The main active constitients were deduced for all new derivaties (Guo et al., 2012).
of C. asitica are pentacyclic triterpenes (asiatic acid, The ELISA method was investigated as an analytical
madecassic acid, asiaticoside, and madecassoside, etc.) tool for quality control and standardization of
(Puttarak and Panichayupakaranant, 2012b). Two new pharmaceutical products containing asiaticoside and
dammarane monodesmosides centellosides A (1) and madecassoside (Juengwatanatrakul et al., 2011;
B (2), and two new natural products ginsenosides Mc Tassanawat et al., 2012). Bioactive compounds
(10) and Y (11), were reported recently (Weng et al., isolated and characterized from C. asiatica are
2011; Han et al., 2012). An efficient microwave- summarized in Table 2 with their physical properties.
assisted extraction method was developed for asiatic
Pharmacological Activity
acid and a sensitive method for quantification of it and
The primary constituents of C. asiatica is the
madecassoside in rat plasma also reported (Han et al.,
triterpenic fractions which showed wide range of
2012; Nasir et al., 2012; Puttarak and Panicha-
defensive and therapeutic effects, most prominently
yupakaranant, 2012a). Asiatic acid has shown
influencing of collagen production and deposition in
numerous therapeutic activities and biotransformation
wound healing. Titrated Extract of Centella asiatica
of it by Penicillium lilacinum ACCC 31890, Fusarium
(TECA) is used to treat several microcirculatory problems,
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Table 2 Structure and biological activities of bioactive compounds isolated from C. asiatica
Name of the compounds Structure Biological activity References

Asiatic acid (C 30 H 48 O 5 ; Aids in generation of neuroglia; promotes wound (Huang et al.,


mw=488.71) healing, promotes cuticle cornification; stimulates 2011; Nasir et
granulation; induces gene expression changes, al., 2011a,
enhancing learning and memory properties, 2012; Zhou et
antinociceptive activity, anti-inflammation activity, al., 2011; Song
acetylcholinesterase inhibitory activity, anti apoptotic et al., 2012;
activity Zhang et al.,
2012)
Asiaticoside (C 48 H 78 O 19 ; Anti-inflammatory; antioxidant induces gene (Tang et al.,
mw=959.15) expression changes, wound healing, reduces scar 2011a; Zhou et
formation, neuroprotective activity, improve collagen al., 2011; Lee
biosynthesis et al., 2012;
Nowwarote et
al., 2012;
Paolino et al.,
2012; Wan et
al., 2012; Xu
et al., 2012a)
Madecassic acid Induces gene expression changes, (Zhou et al.,
(C 30 H 48 O 6 ; 2011; Song et
mw=504.71) al., 2012)

Madecassoside Induces gene expression changes, protection of (Zhou et al.,


(C 48 H 78 O 20 ; endothelial cells from oxidative injury. 2011; Bian et
mw=975.14) al., 2012)

Quercetin (C 15 H 10 O 7 ; Anti-HIV-1, antiasthmatic, antibacterial, (Chong NJ and


mw=302.24) antihepatotoxin, antihypertensive, anti-inflammatory, Aziz, 2011;
antitussive, antiviral, coronary vasodilator, Zhou et al.,
antihypercholesterolemic, 5-HT inhibitor, smooth 2011)
muscle relaxant, platelet aggregation inhibitor,
3’,5’-cAMP-phosphodiesterase inhibitor, fatty acid
synthetase inhibitor, aldose reductase inhibitor (eye
lens), protein kinase C inhibitor; antihypertensive,
reduces blood capillary brittleness, antioxidant

Kaempferol (C 15 H 10 O 6 ; Anti-HIV-1, antibacterial; anti-inflammatory, (Chong NJ and


mw=286.24) antitussive to cure trachitis, antioxidant, ∆5 Aziz, 2011;
-lipoxygenase inhibitor; iodinate thyronine Zhou et al.,
deiodinase inhibitor; aldose reductase inhibitor 2011)

Apigenin (C15H10O5; Antibacterial, antiulcerative, antispasmodic (smooth (Bhandari et


mw=270.24) muscle), diuretic, aldose reductase inhibitor, al., 2007; Zhou
antihypertensive, anti-inflammatory, antioxidant, et al., 2011)
nodulation signal for metabiosis of pea and
Rhizobium leguminosarum,

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Continuing table 2
Name of the compounds Structure Biological activity References

Rutin (C 27 H 30 O 16 ; Anti-inflammatory, antiviral, aldose reductase (Bhandari et


mw=610.53) Inhibitor, insect antifeedant (Heliothis zea), insect al., 2007; Zhou
phagostimulant (Gastrophysa atrocynea), et al., 2011)
antioxidant, inhibits cancer cell invasion, reduces
blood capillary permeability and brittleness

Luteolin (C 15 H 10 O 6 ; Antiallergic, antibacterial, antifungal, cytotoxic, (Bhandari et


mw=286.24) anti-inflammatory, antispasmodic, antitussive, al., 2007; Zhou
antiviral, enhances arterial tension and lowers et al., 2011)
intravenous tension, enhances blood capillary
permeability, immunoenhancer, increases coronary
flow; dihydrocoenzyme I (NADH) oxidase inhibitor,
iodine-induced thyronine deiodinase inhibitor, aldose
reductase inhibitor, anti-inflammatory, anti-HIV
activity

Quercitrin (C 21 H 20 O 11 ; Antibacterial, antineoplastic, antihepatotoxin, (Bhandari et


mw=448.39) anti-inflammatory, antimutagenic, antiviral, diuretic, al., 2007; Zhou
Hemostatic, aldose reductase inhibitor, antioxidant, et al., 2011)
insect antifeedant (Bombyx mor), insect
phagostimulant (Gastrophysa atriocyaea),
hepatoprotective

Naringin (C 27 H 32 O 14 ; Antibacterial, anti-inflammatory, antiviral, aldose (Zheng and


mw=580.55) reductase inhibitor, passive cutaneous anaphylaxis Qin, 2007;
inhibitor Zhou et al.,
2011)

Betulic acid (C 30 H 48 O 3 ; Antineoplastic, cytotoxic, antitubercular, antibacterial (Jamil et al.,


Mw=456.72) 2007; Zhou et
al., 2011)

α-Pinene (C 10 H 16 ; Antifungal, antitussive, irritant. (Barnes et al.,


mw=136.24; 2007; Zhou et
al., 2011)

β-Pinene (C 10 H 16 ; Antifungal, anti-inflammatory, antitussive (Barnes et al.,


mw=136.24; 2007; Zhou et
al., 2011)

Β-caryophyllene (C 15 H 24 ; Flavorant (Barnes et al.,


mw=204.36); 2007; Zhou et
al., 2011)

Linolenic acid Nutrient, inhibits cancer cell invasion, 5α-reductase (Jamil et al.,
(C 18 H 30 O 2 ; inhibitor 2007; Zhou et
mw=278.44) al., 2011)

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Continuing table 2
Name of the compounds Structure Biological activity References

Oleic acid (C 18 H 34 O 2 ; Increases absorption through skin, dermatitis, inhibits (Jamil et al.,
mw=282.47) cancer cell invasion 2007; Zhou et
al., 2011)

Stigmasterol (C 29 H 48 O; Antihypercholesterolemic, antimutagenic, cytotoxic (Barnes et al.,


mw=412.71) inactive, antileishmanial, antimalarial, 2007; Zhou et
antitrypanosomal, platelet aggregation inhibitor, al., 2011)
antiviral

Ascorbic acid (C 6 H 8 O 6 ; Antioxidant, antibacterial, anti-infective, antidote, (Chong NJ and


mw=176.13) antihypercholesterolemic, inhibits production of Aziz, 2011;
Carcinogen, induces tissue to produce collagen, Zhou et al.,
hematopoietic activity 2011)

Nicotinic acid (C 6 H 5 NO 2 ; Antihypercholesterolemic, vasodilator (peripheral) (Chong NJ and


mw=123.11) Aziz, 2011;
Zhou et al.,
2011)

β-Carotene (C 40 H 56 ; EBV-EA activation inhibitor, anti-tumor promoter, (Chong NJ and


mw=536.89) ultraviolet screen, pigment, food additive Aziz, 2011;
Zhou et al.,
2011)
Alanine (C 3 H 7 NO 2 ; Food additive, reverses glucopenia and ketosis (Barnes et al.,
mw=89.09) caused by starvation, glucagon secretion promotor 2007; Zhou et
al., 2011)

Chlorogenic acid Antioxidant, antineoplastic, cytotoxic, antimutagenic, (Chong NJ and


(C 16 H 18 O 9 ; mw=354.32) antiviral, choleretic, hemostatic, leukopoietic, Aziz, 2011;
antimalarial, Zhou et al.,
2011)

Irbic acid Strong radical scavenging, collagenase inhibitory (Antognoni et


(C 28 H 26 O 15 ; mw=602) activity al., 2011)

skin inflammation (eczema, atopic dermatitis, leprosy, asiatica exerts diverse pharmacological activities such
varicose ulcers, etc.) fever, intestinal problems and as antibacterial, antidepresent, antiemetic, antineo-
genitourinary conditions (Belcaro et al., 2011). C. plastic, antioxidant, antithrombotic, anxiolytic,
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gastroprotective, immunomodulatory, antigenotoxic, the proliferation of human gastric adenocarcinoma


nerve regenerative, reproductive, wound healing etc. (MK-1), human uterine carcinoma (HeLa), and murine
due to the presence of several saponin constituents, melanoma (B16F10) cells (Yoshida et al., 2005).
including asiaticoside, asiatic acid, madecassic acid
Anticonvulsant activity: Oral administration of
and some other bioactive compounds (Craker and
different extracts from C. asiatica for 1 week at a dose
Simon, 1986; Koh et al., 2009; Kim et al., 2011).
of 200 mg/kg of body weight of in pentylenetetrazol
Anti-inflammatory activity: Asiatic acid and (induces seizure) induced rats increased the level of
madecassic acid showed anti-inflammatory effect by acetylcholine (neurotransmitter) and decreased the
the inhibition of enzymes (iNOS, cyclooxygenase-2 activity of acetylcholinesterase, causes perceptible
(COX-2)), interleukins (IL-6, IL-1β), cytokine tumor changes in the cholinergic system which indicates the
necrosis factor (TNF-α) expression through the anticonvulsant activity (Visweswari et al., 2010).
down-regulation of NF-κB activation in lipopoly-
Antidepressant activity: Total triterpenes from C.
saccharide (LPS) induced RAW 264.7 murine
asiatica showed reduced immobility time and
macrophage cells (Yun et al., 2008; Won et al., 2010).
ameliorating the imbalance of amino acid levels in
Madecassoside prevented collagen II (CII)-induced
forced swimming mice indicate antidepressant activity
arthritis (CIA) in mice (Liu et al., 2008). Ethanolic
(Chen et al., 2003). Total triterpenes from C. asiatica
extract of C. aiatica at dose 100 mg/kg of body weight
also ameliorated the function of hypothalamic-
showed anti-inflammatory activity in rats similar to
pituitary-adrenal axis (HPA axis), increased the
standard Ibuprofen (George et al., 2009).
contents of monoamine neurotransmitters in rat brain
3,5-dicaffeoyl-4-malonylquinic acid, extract from C.
and reduced the corticosterone level in serum (Chen et
asiatica demonstrated beneficial effect on
al., 2005).
inflammatory bowel disease in rats (Di Paola et al.,
2010). In experimental animal asiaticoside dose Antioxidant activity: C. asiatica possesses potent
inhibited LPS induced fever and inflammatory antioxidant activity, which can exerted neuropro-
response, including serum TNF-α and IL-6 production, tective effect and effect against age related oxidative
liver myeloperoxidase (MPO) activity, brain COX-2 damage in rats brain (Subathra et al., 2005). The
protein expression and prostaglandin E(2) (PGE(2) ) anti-oxidant enzymes, like superoxide dismutase
production (Wan et al., 2012). Asiaticoside G was also (SOD), catalase and glutathione peroxidase (GSHPx)
reported having anti-inflammatory property in were significantly increased, and anti-oxidants like
LPS-stimulated RAW 264.7 cells (Nhiem et al., 2011). glutathione (GSH) and ascorbic acid were decreased
in lymphoma-bearing mice after oral treatment with
Anticancer activity: A large number of experimental
50mg/kg of body weight per day of crude methanol
reports proved that different solvent extracts of C.
extract of C. asiatica for 14 days (Jayashree et al.,
asiatica has anti-cancerous activity. In vitro study on
2003). Administration of aqueous extracts of C.
HeLa, HepG2, SW480 and MCF-7 cell lines showed
asiatica showed to counteract lead-induced oxidative
that methanolic extract had induced apoptosis in
stress male rats (Sainath et al., 2011). Flavonoid
human breast cancerous MCF-7 cells (Babykutty et al.,
compounds were present in aqueous extract of C.
2009). Water extracts induced apoptosis in colonic
asiatica, showed highest antioxidant property (Pittella
crypts and exerted chemopreventive effect on colon
et al., 2009). The antioxidant properties of essential
tumorigenesis in male F344 rats (Bunpo et al., 2004).
oils and various extracts of this plant may be a great
Asiatic acid induced apoptosis in human melanoma
interest in food industry, since their possible use as
SK-MEL-2 cells (responsible for skin cancer) and
natural additives. To study the antioxidant properties
SW480 human colon cancer cells (Park et al., 2005;
and phenolic compounds present in C. asiatica, the
Tang et al., 2009). Asiaticoside enhanced anti-tumor
optimum brewing procedure was studied to use as
activity of vincristine in cancer cells (Huang et al.,
herbal teas (Ariffin et al., 2011).
2004). Constituents in the methanol extract inhibited
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Antiulcer activity: C. asiatica showed significant al., 2010).


protection against ethanol, aspirin, cold restraint stress
Effect on Skin: Asiaticoside stimulated skin aging
and pyloric ligation induced gastric ulcers in rats when
inhibitor type 1 collagen synthesis in human dermal
200 mg/kg and 600 mg/kg of body weight of fresh
fibroblast cells and potential use in the treatment
juice was given orally twice daily for five days
and/or prevention of hypertrophic scars and keloids
(Sairam et al., 2001). Water extract of C. asiatica
was recommended (Lee et al., 2006; Tang et al.,
containing asiaticoside were found to reduce the size
2011b). Alcoholic extract of C. asiatica showed useful
of the acetic acid induced gastric ulcers in rats (Guo et
effects in pruritis and other skin disease (Gohil et al.,
al., 2004).
2010). Hydroalcoholic extract of C. asiatica was used
Anxiolytic activity: 12 g oral single dose of C. to be made herbal creams along with four medicinal
asiatica after 60 minutes significantly attenuated the plants (Curcuma caesia, Areca catechu, Cinnamon
acoustic startle response (ASR) in human (Bradwejn zeylanicum and Tamarindus indica) which showed
et al., 2000). The elevated plus maze (EPM) test for increased skin hydration, sebum levels, viscoelasticity,
5 minutes revealed that administration of standardized and decreased melanin content (Saraf et al., 2012).
extract, methanol and ethyl acetate extracts as well as Asiaticoside promotes skin cell behaviours involved
pure asiaticoside had imparted anxiolytic activity in in wound healing by increasing migration rates of skin
rats (Wijeweera et al., 2006; Wanasuntronwong et al., cells, enhancing the initial skin cell adhesion, inducing
2012). Medication of 500 mg/capsule (concentrated an increase in the number of normal human dermal
lyophilized of 70% hydro-ethanolic extract of C. fibroblasts (Lee et al., 2012). Aqueous extract of C.
asiatica), twice daily, after meal for 60 days in 33 asiatica was nano-encapsulated with gelatin and
patient (18 male and 15 female; average age 33 efficiently reduced the expression of matrix
years) in Kolkata (India) demonstrated that C. metalloproteinase (MMP)-1 in UV-irradiated cells and
asiatica not only significantly had attenuated inhibited hyaluronidase expression in mouse skin
anxiety related disorders but it also significantly (Kwon et al., 2012).
had reduced stress phenomenon and its correlated
Immunomodulating activity: Triterpenoid saponins
depression (Jana et al., 2010).
of C. asiatica showed immunomodulatory effect
Cardioprotective activity: Administration of alcoholic (Plohmann et al., 1997). Methanolic extract of C.
extract of C. asiatica at a dose of 1000 mg/kg of body asiatica dramatically increased phagocytic index and
weight in Laboratory bred Sprague–Dawley rats total WBC in Swiss Albino mice (Jayathirtha and
significantly reduced the necrosis of the myocardium Mishra, 2004). Administration of water extract of C.
(Pragada et al., 2004). C. asiatica extract asiatica significantly increased proliferation and the
demonstrated the cardioprotective effect at a dose of production of IL-2 and TNF-α in human peripheral
200 mg/kg of body weight in adult male albino rats of blood mononuclear cells (PBMCs) but ethanol extract
Wistar strain on antioxidant tissue defense system had inhibitory effect (Punturee et al., 2005). Asiatic
during adriamycin induced cardiac damage (Gnana- acid and C. asiatica ethanol and dichloromethane
pragasam et al., 2004). Madecassoside showed protective extracts showed inhibitory effect on three major
effect on myocardial ischemiareperfusion injury in cDNA, which expressed human cytochrome P450
rabbits and rats (Li et al., 2007; Bian et al., 2008). (CYP2C9, CYP2D6 and CYP3A4) isoforms (Pan et
al., 2010).
Hepatoprotective activity: Total glucosides extract of
C. asiatica showed significant anti-liver fibrosis effect Radioprotective activity: Aqueous extract C. asiatica
in dimethylnitrosamine induced liver fibrosis in rats showed more radioprotective effect than standard drug
(Ming et al., 2004). Asiaticoside revealed hepatopro- “ondansetron” against conditioned taste aversion
tective effect against acute liver injury induced by (behavioural perturbation) induced by 60Co-γ
lipopolysaccharide/D-galactosamine in mice (Zhang et irradiation at low dose 2Gy in male rats (Shobi and
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Goel, 2001). Administration of 100 mg/kg of body pure substance) were prepared and evaluated for
weight of aqueous extract of C. asiatica, just 1 hour wound dressings and loaded herbal substances were
before irradiation with 8Gy 60Co- γ rays was found found stable up to 4 months, promotes proliferation
most radioprotective in Swiss Albino Mouse (Sharma and upregulating the production of collagen of the
and Sharma, 2002) and further study revealed that seeded (Suwantong et al., 2010). The clinical efficacy
100mg/kg of body weight of dried powdered extract and side effects of the oral C. asiatica extract capsule
of C. asiatica had found to be effective against in the diabetic wound healing was investigated
modified 60Co-γ irradiation induced damage in the (Paocharoen, 2010). Madecassoside showed enhance
mouse liver (Sharma and Sharma, 2005). 70% wound-healing and diminish keloid formation in
ethanolic extract of C. asiatica significantly reduced primary keloid-derived fibroblasts, originating from
radiation-induced damage to DNA (Joy and Nair, human earlobe keloids (Song et al., 2012).
2009). microRNA (miRNA) expression profiling
Memory enhancing Activity: Since the ancient time,
analysis was used to evaluate the protective effects of
C. asiatica is used to enhance intelligence and
C. asiatica against Ultraviolet B damage in human
improve cognitive function. Oral administration with
keratinocytes, disclosed that miRNAs with altered
200 mg/kg of body weight aqueous extract during
expression were functionally related with cell
postnatal development stage increased brain function
proliferation and inhibition of apoptosis, may prevent
in juvenile and young adult mice (Rao et al., 2005).
the skin damage (An et al., 2012).
Enhanced working memory and improved self-rated
Wound healing activity: A large number of reports mood were observed in 28 patients after higher dose
have been found about the wound healing activity of administration of C. asiatiac extract preparations
C. asiatica (Temrangsee et al., 2011). Aqueous extract (Wattanathorn et al., 2008). Asiatic acids isolated from
of C. asiatica was used to formulate ointment, cream C. asiatica showed enhancing learning and memory
and gel, which evaluate for wound healing in rats properties in male Spraque–Dawley rats (Nasir et al.,
showed faster epithelialisation and higher rate of 2011b).
wound contraction (Sunilkumar et al., 1998).
Burns: C. asiatica extract and its active constituents
Dexamethasone suppressed wound in Wistar Albino
are very effective against burns caused by boiling
rats could be healed by ethanolic leaf extracts as like
water, electric current or gas exploitation.
as normal model (Shetty et al., 2006). In a recent
Combination of C. asiatica extract with an antibiotic
study in 200 diabetic patients revealed positive result
was anti-infectious beside healing burns (Salas et al.,
with C. asiatica extracted capsule without any adverse
2005). Low dose 10−8% to 10−12% (w/w) of
effect in the department of Surgery, Thammasat
asiaticoside application facilitated repairing in mice
University Hospital (Paocharoen, 2010). Wound
burned wound (Kimura et al., 2008).
healing activity of asiaticoside was also reported in
guinea pig model at dose 1 mg/kg of body weight and Anti-psoriatic Activity: C. asiatica shows anti-
in the chick chorioallantoic membrane model at psoriatic effect on SVK-14 keratinocyte due to the
concentration 40 µg/disk (Shukla et al., 1999). The presence of triterpenoid glycosides (Sampson et al.,
effects of asiaticoside in human periodontal ligament 2001).
cells (HPDLs) proliferation, protein synthesis, and
osteogenic differentiation were investigated and Antimicrobial Activity: C. asiatica shows
showed enhanced periodontal tissue healing antibacterial activity on both Gram positive and Gram
(Nowwarote et al., 2012). At low concentrations negative bacteria. Growth inhibition of Gram positive
aqueous extract of C. asiatica promote epithelium Bacillus subtilis and Gram negative Pseudomonas
wound healing in rabbit corneal epithelial (RCE) cells aeruginosa, P. cichorii and Escherichia coli was
(Ruszymah et al., 2012). Ultra-fine cellulose acetate observed in the disc diffusion test of hexane and ethyl
fiber mats containing asiaticoside (in crude extract or acetate extracts of C. asiatica (Escop and

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Phytotherapy, 2003). 1 000 µg/disc of hot methanolic which could be significantly improved in six weeks by
extract is moderately effective on Staphylococcus administration of C. asiatica (150 and 300 mg/kg of
aureus and Methicillin Resistant S. aureus (Wild Type) body weight) (Kumar et al., 2011). Chronic aluminum
(Zaidan et al., 2005). Micobacterium tuberculosis and exposure in rat induce cognitive dysfunction, apoptosis,
M. leprae were reported to be more sensitive to oxidative stress and mitochondrial enzyme alteration
liposomal asiatocoside than free asiatocoside (Fugh- and administration of C. asiatica found significantly
Berman, 2003). Higher antiviral activity was also decreased aluminum concentration, improved memory
reported with aqueous extract of C. asiatica against performance, oxidative defense, acetylcholinestrease
type 2 Herpes simplex virus (Escop and Phytotherapy, activity, caspase-3 and reversal of mitochondrial
2003). enzyme activity as compared to control (Prakash and
Kumar, 2012). The psychoactive and antioxidant role
Lervicidal Activity: Haemaphysalis bispinosa (the
of ethanolic extract of C. asiatica in middle cerebral
adult cattle tick), Paramphistomum cervi (sheep fluke),
artery occlusion (MCAO) in rats was evaluated and
Anopheles subpictus and Culex tritaeniorhynchus
revealed that administration of C. asiatica extract
showed sensitivity to hexane, chloroform, ethyl
restored histological morphology of brain, diminished
acetate, acetone, methanol extract of C. asiatica but
infarction volume, greatly improved the
methanol extract was the most effective on P. cervi
neurobehavioral activity (Tabassum et al., 2012).
and A. subpictus (Bagavan et al., 2009). 3-O-[a-L-
arabinopyranosyl] 2 a, 3 ß, 6 ß, 23-a tetrahydroxyurs- Asiatic acid possess neuroprotective effects in vitro
12-ene-28-oic acid, a triterpenoid glycoside, exhibited and in vivo (Xu et al., 2012b), nootropic activity with
inhibitory activity against larvae of Spilarctia oblique therapeutic implications for patients with memory loss
(Shukla et al., 2000). (Shinomol et al., 2011). Increased dendritic length and
branches was observed in rat after fresh leaves extract
Anti-hyperglycemic effect: Oral administration of
administration (Mohandas Rao et al., 2006). Three
asiatic acid and glibenclamide to streptozotocin
derivatives of asiatic acid were significantly effective
induced diabetic rats for 45 days prevented the altered
in protecting excess glutamate exposed neurons on
activities of key enzymes (glucose-6-phosphatase and
cultured cortical cells (Lee et al., 2000; Xu et al.,
fructose-1,6-bisphosphatase) related with hypergly-
2012b). Non-polar fraction of ethanolic extract
cemia (Ramachandran and Saravanan, 2012).
containing asiatic acid which found to be increased in
Neuroprotective Activity: Aqueous extract showed neurite outgrowth in human SH-SY5Y cells in the
neuroprotective effect by increasing the antioxidant presence of nerve growth factor and administration of
enzyme level in mice corpus striatum and ethanolic extract through drinking water demonstrated
hippocampus (Haleagrahara and Ponnusamy, 2010). axonal regeneration in Male Sprague-Dawley rats
Fresh leaf extract of C. asiatica was investigated on (Soumyanath et al., 2005). Asiatic acid was reported
dendritic morphology of amygdaloid neurons on adult for the treatment of cerebral ischemia in mice
rats, one of the regions concerned with learning and (Krishnamurthy et al., 2009). Asiatic acid showed
memory, showed a significant increase in the dendritic potential neuroprotective activity against
length and branching points (Rao et al., 2012). Water C2-ceramides-induced cell death in primary cultured
extract of C. asiatica inhibit the activity of subtypes of rat cortical neuronal cells (Zhang et al., 2012) and
phospholipase A2 (PLA2), which is related with asiaticoside significantly attenuated 1-methyl-4-
neurodegenerative disease (Defillipo et al., 2012). phenyl-1,2,3,6-tetrahydropyridine (MPTP) induce
n-hexane, chloroform, ethyl acetate, n-butanol extract Parkinsonism in rat model (Xu et al., 2012a).
of C. asiatica showed anticonvulsant and neuropro- Asiaticoside was recommended for epilepsy, stroke,
tective activity in male albino rats (Visweswari et al., multiple sclerosis and other neuropsychiatric disorders
2010). D-galactose induced oxidative and mitochon- (Barbosa et al., 2008).
drial dysfunction and cognitive impairment in mice,
Venous insufficiency Activity: Patients suffering
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from venous hypertension were positively effective to In vitro propagation


an oral preparation of total triterpenic fraction of C. Optimum shoots development of C. asiatica were
asiatica (TTFCA) in the improvement of microcir- achieved in Duchefa medium supplemented with
culation and edema (leg volume) in venous 2 mg/L 6 benzylaminopurine (BAP) and 0.1 mg/L
microangiopathy (Cesarone et al., 2001). C. asiatica 1-naphthaleneacetic acid (NAA) (Moghaddam et al.,
exract regulated mucopolysachharide metabolism in 2011), Murashige and Skoog medium supplemented
connective tissue in patient with varicose veins with 2.5 mg/L kinetin (Prasad et al., 2012). Rooting
(Arpaia et al., 1990). However, a large number of can be done on full-strength MS medium containing
similar studies were reported on venous insufficiency. 0.5 mg/L indole-3-butyric acid (IBA) (Moghaddam et
al., 2011). Varying level of asiaticoside content in
Others: Asiaticoside was revealed as protective
shoot could be achieved with the varying ratio of
against cecal ligation and puncture (CLP) induced
NH4+-N:NO3--N or Cu2+ concentration in the medium
lung injury in mice (Zhang et al., 2010). This plant
(Prasad et al., 2012).
also increases vigority (Mato et al., 2011). C. asiatica
extract in combination with Punica granatum Conclusion
significantly improved clinical signs of chronic Since the time of immemorial C. asiatica is being
periodontitis in 15 patients (Sastravaha et al., 2005). used for the treatment of wide range of maladies. So
Whole gene expression level were analyzed using far, the reports on bioactivity and clinical trials in
microarrays in human dermal fibroblasts (HDFs) to different models and human concern the asiaticoside
determine whether H 2 O 2 -induced senescence is and its derivatives. Recent studies have confirmed the
affected by C. asiatica extracts to characterized the efficacy of this plant and its constituents and extracts
activity of extract in stress-induced premature to injury, leprosy, tuberculosis, cancer, aging,
senescence (SIPS) and found that 39 mRNAs are gastrointestinal disease, skin disease, neurological
expressed differentially includes genes that regulate disorder, cardiovascular problems, ulcer, radiation,
cell growth, apoptosis, DNA replication, transcription, respiratory problems and so on. However, further
gene silencing, senescence and the spindle checkpoint clinical research are essential which can establish the
(Kim et al., 2011). Oral administration of water extract C. asiatica as a potential source of standard drugs.
of C. asiatica protected the toxicity induced by
Reference
exogenously added and endogenously generated An I.S., An S., Kang S.M., Choe T.B., Lee S.N., Jang H.H., and
β-amyloid in the Tg2576 mouse, which is a murine Bae S., 2012, Titrated extract of Centella asiatica provides
model of Alzheimer’s disease with high β-amyloid a UVB protective effect by altering microRNA expression
burden in SH-SY5Y cells and MC65 human profiles in human dermal fibroblasts, International Journal
neuroblastoma cells from (Soumyanath et al., 2012). of Molecular Medicine, 30: 1194–1202
Antognoni F., Perellino N.C., Crippa S., Dal Toso R., Danieli
Contradictions: Clinical study in patients suffering B., Minghetti A., Poli F., and Pressi G., 2011, Irbic acid, a
from jaundice showed that all patients had improved dicaffeoylquinic acid derivative from Centella asiatica
cell cultures, Fitoterapia, 82: 950-954, http://dx.doi.org/10.
with C. asiatica discontinuation and deteriorated after
1016/ j.fitote. 2011.05.008
retaking due to having hepatotoxic effect (Jorge and Ariffin F., Heong Chew S., Bhupinder K., Karim A.A., and
Jorge, 2005). This plant is not applicable for children, Huda N., 2011, Antioxidant capacity and phenolic
pregnant and lactated women (Koh et al., 2009). composition of fermented Centella asiatica herbal teas,
Journal of the Science of Food and Agriculture, 91:
Traditional uses 2731-2739, http://dx.doi.org/10.1002/jsfa.4454
Traditionally C. asiatica is used to treat differents Arpaia M.R., Ferrone R., Amitrano M., Nappo C., Leonardo G.,
aliments in different countries for over a long time. and Del Guercio R., 1990, Effects of Centella asiatica
Traditional uses of C. asiatica are summarized in extract on mucopolysaccharide metabolism in subjects
with varicose veins, International Journal of Clinical
Table 3.
Pharmacology Research, 10: 229–233

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Table 3 Traditional uses of C. asiatica in different regions for different purposes


Regions Traditional Uses References
Brazil Elephantiasis, uterine cancer, leprosy (Leonard,
2006)
China Bleeding, scabies and tinea / ringworm, skin ulcers, rash, and redness, abdominal pain, diarrhea, (Leonard,
dysentery, vomiting, red eyes, swollen throat, tonsillitis, nosebleeds, jaundice, infectious 2006; Koh et
hepatitis, boils, fistulas, furuncles and carbuncles with toxic swelling, fever, trauma, falls, al., 2009)
contusion, fractures, childhood tidal fevers, measles, asthma, bronchitis, respiratory problems,
tuberculosis, pleurisy, urinary difficulty with stones or bleeding, arsenic poisoning, fear of cold,
dizziness, leprosy, scrofula, improve of appetite, digestion
Europe Varicose veins (Leonard,
2006)
Fiji Skin ulcers, rash, and redness, pimples, stomachache, bleeding ulcer, constipation, hemorroids, (Leonard,
eye problems, fractures, painful and swollen joints, rib pain, hildhood convulsions, post partum 2006)
weakness, unwanted pregnancy
Hawai'i Blotchy skin, cold extremities, white fingers, poor memory, impotence due to vascular disease, (Leonard,
2006)
India Eczema, skin ulcers, rash, and redness, abscesses, peptic ulcer, cataract, eye problems, fever, (Leonard,
cholera, abdominal tumor, anxiety neurosis, insanity, poor memory, general debility, blood 2006; Koh et
disease al., 2009)
Indonesia Wounds, colic (Koh et al.,
2009)
Malagasy Leprosy (Leonard,
2006)
Malaya Dermatosis (Leonard,
2006)
Mauritius Cancer (Leonard,
2006)
Nepal Indigestion, rheumatism, poor memory, syphilis, general debility, leprosy (Leonard,
2006)
Philippines Dysentery, headache, fever, wounds (Leonard,
2006)
Samoa Eye problems, migraines, boils, fistulas, furuncles and carbuncles with toxic swelling, venereal (Leonard,
disease, leprosy 2006)
Tonga Juiced for eye ailments and nasally for migraines, convulsions, delayed closure of the fonatel, (Leonard,
navel infection in babies 2006)
Turkey Spasms, leprosy (Leonard,
2006)

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