ArticlePDF Available

Current updates on Centella asiatica: Phytochemistry, pharmacology and traditional uses

January 2013

Authors:

Dipankar Chandra Roy

Bangladesh Council of Scientific and Industrial Research

Shital K. Barman

University of Newcastle Australia

Md Munan Shaik

Boston Children's Hospital, Harvard Medical School

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.

Content uploaded by Dipankar Chandra Roy

Content may be subject to copyright.

Content uploaded by Md Munan Shaik

Content may be subject to copyright.

Medicinal Plant Research 2013, Vol.3, No.4, 20

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

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

medical sector. Around 5 000 species have specific

therapeutic value among 250 000 higher plant species

on earth (Joy et al., 1998). Centella asiatica has a long

history in ancient Ayurvedic remedy, used in wound

healing, cleansing for skin problem and digestive

disorders (Chevallier, 2001) and effective in treatment

of stomach ulcers, mental fatigue, diarrhea, epilepsy,

hepatitis, syphilis and asthma (Goldstein and

Goldstein, 2012). Such traditional uses and reputation

of this species cross over the boundary limit of

Bangladesh, India, and Srilanka and now extensively

used in the West (Chevallier, 2001; Meulenbeld and

Wujastyk, 2001). C. asiatica and Hydrocotyle asiatica,

belongs to family Apiaceae (Umbelliferae) are used

synonymously and commonly known as Thankuni

(Bengali), Bemgsag/Brahma-Manduki/Gotukola/Khu-

lakhudi/Mandookaparni (Hindi), Indian Pennywort/

Marsh Pennywort/ Gotu kola (English) (Singh et al.,

2010). C. asiatica is creeping, perennial herb with up

to 2m long slender and tender horizontal reddish

prostrate stolons, characterized by long rooting

internodes (Jamil et al., 2007; Koh et al., 2009).

Glabrous leaves, 1-3 arising from each node of the

stems, are green, fan-shaped or round renifrom,

1.4 cm by 1.7 cm with crenate or dentate margin

(Jamil et al., 2007; Koh et al., 2009). Flowers

occurring in July- September are umbels with 3-4

white or light purple-to-pink petals bearing 4mm long

oval to globular shaped fruit (Chauhan, 1999; Jamil et

al., 2007; Koh et al., 2009). The most used part for

medicinal purposes is dried whole plant, leaves and

stems. C. asiatica plant is indigenous to Bangladesh,

India, West Pakistan, China, Japan, America and the

pacific (Koh et al., 2009). This plant is commonly

seen in moist, sandy or clayey soils waste places

(Jamil et al., 2007).

Phytochemistry

C. asiatica is a rich source of amino acids, flavonoids,

terpenoids, essential oils, alkaloids etc. (Table 1).

Most of the phytochemical studies concentrated on

leaves and the constituents vary depending upon the

geographical distribution (Chong and Aziz, 2011).

Medicinal Plant Research 2013, Vol.3, No.4, 20

http://mpr.sophiapublisher.com

Table 1 Chemical constituents of C. asiatica

Main groups

Constituents

References

Amino acids

Alanine and serine (major components), aminobutyrate, aspartate, glutamate,

histidine, lysine, threonine, arginine, leucine, iso-leucine, valine, methionine,

tyrosine, phenylalanine, proline, cystine, glycine.

(Barnes et al., 2007;

Chong NJ and Aziz,

2011),

Carbohydrates

Glucose, mesoinositol, centellose, pectin, arabinogalactan

(Chong NJ and Aziz,

2011)

Phenols

Flavonoids: Kaempferol, kaempferol-3-o-β-d-glucuronide, castilliferol, quercetin,

quercetin-3-o-β-d-glucuronide, castillicetin, apigenin, rutin, luteolin, naringin

(Bhandari et al., 2007;

Zheng and Qin, 2007;

Chong NJ and Aziz,

2011)

Phenylpropanoids: Rosmarinic acid, chlorogenic acid, 3,4-di-o-caffeoyl quinic acid,

1,5-di-o-caffeoyl quinic acid, 3,5-di-o-caffeoyl quinic acid, 4,5-di-o-caffeoyl quinic

acid, isochlorogenic acid

(Chong NJ and Aziz,

2011)

Tannin: Tannin, phlobatannin

(Chong NJ and Aziz,

2011)

Terpenoids

Triterpenes, asiaticoside, centelloside, madecassoside, brahmoside, brahminoside

(saponin glycosides), asiaticentoic acid, centellic acid, centoic acid, madecassic

acid, terminolic acid and betulic acid.

(Barnes et al., 2007;

Jamil et al., 2007)

Volatile oils and

fatty oils

Various terpenoids: β-caryophyllene, trans β-farnesene and germacrene D

(sesquiterpenes), α-pinene and β-pinene.

Fatty acids: linoleic acid, linolenic acid, lignocene, oleic acid, palmitic acid, stearic

acid.

(Barnes et al., 2007;

Jamil et al., 2007)

Vitamins

Ascorbic acid, nicotinic acid, β-carotene

(Chong NJ and Aziz,

2011)

Mineral

Calcium, phosphorus, iron, potassium, magnesium, manganese, zinc, sodium,

copper

(Chong NJ and Aziz,

2011)

Other constituents

Hydrocotylin (an alkaloid), vallerine (a bitter principle), phytosterols (e.g.

campesterol, sitosterol, stigmasterol), resin. ~14 different polyacetylenes

(8-acetoxycentellynol, cadiyenol, dotriacont-8-en-1-oic acid, 11-oxoheneicosanyl

cyclohexane).

(Barnes et al., 2007;

Chong NJ and Aziz,

2011)

Bioactive compounds

C. asiatica is being used as a natural source of

medicine for long time. The main active constitients

of C. asitica are pentacyclic triterpenes (asiatic acid,

madecassic acid, asiaticoside, and madecassoside, etc.)

(Puttarak and Panichayupakaranant, 2012b). Two new

dammarane monodesmosides centellosides A (1) and

B (2), and two new natural products ginsenosides Mc

(10) and Y (11), were reported recently (Weng et al.,

2011; Han et al., 2012). An efficient microwave-

assisted extraction method was developed for asiatic

acid and a sensitive method for quantification of it and

madecassoside in rat plasma also reported (Han et al.,

2012; Nasir et al., 2012; Puttarak and Panicha-

yupakaranant, 2012a). Asiatic acid has shown

numerous therapeutic activities and biotransformation

of it by Penicillium lilacinum ACCC 31890, Fusarium

equiseti CGMCC 3.3658, and Streptomyces griseus

CGMCC 4.18 strains was investigated and structure

were deduced for all new derivaties (Guo et al., 2012).

The ELISA method was investigated as an analytical

tool for quality control and standardization of

pharmaceutical products containing asiaticoside and

madecassoside (Juengwatanatrakul et al., 2011;

Tassanawat et al., 2012). Bioactive compounds

isolated and characterized from C. asiatica are

summarized in Table 2 with their physical properties.

Pharmacological Activity

The primary constituents of C. asiatica is the

triterpenic fractions which showed wide range of

defensive and therapeutic effects, most prominently

influencing of collagen production and deposition in

wound healing. Titrated Extract of Centella asiatica

(TECA) is used to treat several microcirculatory problems,

Medicinal Plant Research 2013, Vol.3, No.4, 20

http://mpr.sophiapublisher.com

Table 2 Structure and biological activities of bioactive compounds isolated from C. asiatica

Name of the compounds

Structure Biological activity References

Asiatic acid (C

;

mw=488.71)

Aids in generation of neuroglia; promotes wound

healing, promotes cuticle cornification; stimulates

granulation; induces gene expression changes,

enhancing learning and memory properties,

antinociceptive activity, anti-inflammation activity,

acetylcholinesterase inhibitory activity, anti apoptotic

activity

(Huang et al.,

2011; Nasir et

al., 2011a,

2012; Zhou et

al., 2011; Song

et al., 2012;

Zhang et al.,

2012)

Asiaticoside (C

;

mw=

959.15)

Anti-inflammatory; antioxidant induces gene

expression changes, wound healing, reduces scar

formation, neuroprotective activity, improve collagen

biosynthesis

(Tang et al.,

2011a; Zhou et

al., 2011; Lee

et al., 2012;

Nowwarote et

al., 2012;

Paolino et al.,

2012; Wan et

al., 2012; Xu

et al., 2012a)

Madecassic acid

30H48 O6;

mw=504.71)

Induces gene expression changes,

(Zhou et al.,

2011; Song et

al., 2012)

Madecassoside

(

C48H78 O20 ;

mw=

975.14)

Induces gene expression changes, protection of

endothelial cells from oxidative injury.

(Zhou et al.,

2011; Bian et

al., 2012)

Quercetin (C

;

mw=

302.24)

Anti-HIV-1, antiasthmatic, antibacterial,

antihepatotoxin, antihypertensive, anti-inflammatory,

antitussive, antiviral, coronary vasodilator,

antihypercholesterolemic, 5-HT inhibitor, smooth

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

(Chong NJ and

Aziz, 2011;

Zhou et al.,

2011)

Kaempferol (C

;

mw=

286.24)

Anti-HIV-1, antibacterial; anti-inflammatory,

antitussive to cure trachitis, antioxidant, ∆5

-lipoxygenase inhibitor; iodinate thyronine

deiodinase inhibitor; aldose reductase inhibitor

(Chong NJ and

Aziz, 2011;

Zhou et al.,

2011)

Apigenin (

C15H10O5;

mw=

270.24)

Antibacterial, antiulcerative, antispasmodic (smooth

muscle), diuretic, aldose reductase inhibitor,

antihypertensive, anti-inflammatory, antioxidant,

nodulation signal for metabiosis of pea and

Rhizobium leguminosarum,

(Bhandari et

al., 2007; Zhou

et al., 2011)

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Continuing table 2

Name of the compounds

Structure Biological activity References

Rutin (

C27H30 O16 ;

mw=

610.53)

Anti-inflammatory, antiviral, aldose reductase

Inhibitor, insect antifeedant (Heliothis zea), insect

phagostimulant (Gastrophysa atrocynea),

antioxidant, inhibits cancer cell invasion, reduces

blood capillary permeability and brittleness

(Bhandari et

al., 2007; Zhou

et al., 2011)

Luteolin (

C15H10 O6;

mw=

286.24)

Antiallergic, antibacterial, antifungal, cytotoxic,

anti-inflammatory, antispasmodic, antitussive,

antiviral, enhances arterial tension and lowers

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

(Bhandari et

al., 2007; Zhou

et al., 2011)

Quercitrin (C

;

mw=

448.39)

Antibacterial, antineoplastic, antihepatotoxin,

anti-inflammatory, antimutagenic, antiviral, diuretic,

Hemostatic, aldose reductase inhibitor, antioxidant,

insect antifeedant (Bombyx mor), insect

phagostimulant (Gastrophysa atriocyaea),

hepatoprotective

(Bhandari et

al., 2007; Zhou

et al., 2011)

Naringin (C

;

mw=580.55)

Antibacterial, anti-inflammatory, antiviral, aldose

reductase inhibitor, passive cutaneous anaphylaxis

inhibitor

(Zheng and

Qin, 2007;

Zhou et al.,

2011)

Betulic acid (C

30H48 O3;

Mw=

456.72)

Antineoplastic, cytotoxic, antitubercular, antibacterial (Jamil et al.,

2007; Zhou et

al., 2011)

-Pinene (C10H16;

mw=136.24;

Antifungal, antitussive, irritant. (Barnes et al.,

2007; Zhou et

al., 2011)

-Pinene (C10H16;

mw=136.24;

Antifungal, anti-inflammatory, antitussive (Barnes et al.,

2007; Zhou et

al., 2011)

-caryophyllene (C15H24;

mw=204.36);

Flavorant (Barnes et al.,

2007; Zhou et

al., 2011)

Linolenic acid

18H30 O2;

mw=278.44)

Nutrient, inhibits cancer cell invasion, 5α-reductase

inhibitor

(Jamil et al.,

2007; Zhou et

al., 2011)

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Continuing table 2

Name of the compounds

Structure Biological activity References

Oleic acid

(C18 H34 O2;

mw=282.47)

Increases absorption through skin, dermatitis, inhibits

cancer cell invasion

(Jamil et al.,

2007; Zhou et

al., 2011)

Stigmasterol (C

29H48 O;

mw=412.71)

Antihypercholesterolemic, antimutagenic, cytotoxic

inactive, antileishmanial, antimalarial,

antitrypanosomal, platelet aggregation inhibitor,

antiviral

(Barnes et al.,

2007; Zhou et

al., 2011)

Ascorbic acid (C

;

mw=176.13)

Antioxidant, antibacterial, anti-infective, antidote,

antihypercholesterolemic, inhibits production of

Carcinogen, induces tissue to produce collagen,

hematopoietic activity

(Chong NJ and

Aziz, 2011;

Zhou et al.,

2011)

Nicotinic acid (

C6H5NO2;

mw=123.11)

Antihypercholesterolemic, vasodilator (peripheral) (Chong NJ and

Aziz, 2011;

Zhou et al.,

2011)

β-Carotene (C

;

mw=536.89)

EBV-EA activation inhibitor, anti-tumor promoter,

ultraviolet screen, pigment, food additive

(Chong NJ and

Aziz, 2011;

Zhou et al.,

2011)

Alanine (C

;

mw=89.09)

Food additive, reverses glucopenia and ketosis

caused by starvation, glucagon secretion promotor

(Barnes et al.,

2007; Zhou et

al., 2011)

Chlorogenic acid

16H18 O9; mw=354.32)

Antioxidant, antineoplastic, cytotoxic, antimutagenic,

antiviral, choleretic, hemostatic, leukopoietic,

antimalarial,

(Chong NJ and

Aziz, 2011;

Zhou et al.,

2011)

Irbic acid

28H26 O15 ; mw=602)

Strong radical scavenging, collagenase inhibitory

activity

(Antognoni et

al., 2011)

skin inflammation (eczema, atopic dermatitis, leprosy,

varicose ulcers, etc.) fever, intestinal problems and

genitourinary conditions (Belcaro et al., 2011). C.

asiatica exerts diverse pharmacological activities such

as antibacterial, antidepresent, antiemetic, antineo-

plastic, antioxidant, antithrombotic, anxiolytic,

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

gastroprotective, immunomodulatory, antigenotoxic,

nerve regenerative, reproductive, wound healing etc.

due to the presence of several saponin constituents,

including asiaticoside, asiatic acid, madecassic acid

and some other bioactive compounds (Craker and

Simon, 1986; Koh et al., 2009; Kim et al., 2011).

Anti-inflammatory activity: Asiatic acid and

madecassic acid showed anti-inflammatory effect by

the inhibition of enzymes (iNOS, cyclooxygenase-2

(COX-2)), interleukins (IL-6, IL-1β), cytokine tumor

necrosis factor (TNF-α) expression through the

down-regulation of NF-κB activation in lipopoly-

saccharide (LPS) induced RAW 264.7 murine

macrophage cells (Yun et al., 2008; Won et al., 2010).

Madecassoside prevented collagen II (CII)-induced

arthritis (CIA) in mice (Liu et al., 2008). Ethanolic

extract of C. aiatica at dose 100 mg/kg of body weight

showed anti-inflammatory activity in rats similar to

standard Ibuprofen (George et al., 2009).

3,5-dicaffeoyl-4-malonylquinic acid, extract from C.

asiatica demonstrated beneficial effect on

inflammatory bowel disease in rats (Di Paola et al.,

2010). In experimental animal asiaticoside dose

inhibited LPS induced fever and inflammatory

response, including serum TNF-α and IL-6 production,

liver myeloperoxidase (MPO) activity, brain COX-2

protein expression and prostaglandin E(2) (PGE(2) )

production (Wan et al., 2012). Asiaticoside G was also

reported having anti-inflammatory property in

LPS-stimulated RAW 264.7 cells (Nhiem et al., 2011).

Anticancer activity: A large number of experimental

reports proved that different solvent extracts of C.

asiatica has anti-cancerous activity. In vitro study on

HeLa, HepG2, SW480 and MCF-7 cell lines showed

that methanolic extract had induced apoptosis in

human breast cancerous MCF-7 cells (Babykutty et al.,

2009). Water extracts induced apoptosis in colonic

crypts and exerted chemopreventive effect on colon

tumorigenesis in male F344 rats (Bunpo et al., 2004).

Asiatic acid induced apoptosis in human melanoma

SK-MEL-2 cells (responsible for skin cancer) and

SW480 human colon cancer cells (Park et al., 2005;

Tang et al., 2009). Asiaticoside enhanced anti-tumor

activity of vincristine in cancer cells (Huang et al.,

2004). Constituents in the methanol extract inhibited

the proliferation of human gastric adenocarcinoma

(MK-1), human uterine carcinoma (HeLa), and murine

melanoma (B16F10) cells (Yoshida et al., 2005).

Anticonvulsant activity: Oral administration of

different extracts from C. asiatica for 1 week at a dose

of 200 mg/kg of body weight of in pentylenetetrazol

(induces seizure) induced rats increased the level of

acetylcholine (neurotransmitter) and decreased the

activity of acetylcholinesterase, causes perceptible

changes in the cholinergic system which indicates the

anticonvulsant activity (Visweswari et al., 2010).

Antidepressant activity: Total triterpenes from C.

asiatica showed reduced immobility time and

ameliorating the imbalance of amino acid levels in

forced swimming mice indicate antidepressant activity

(Chen et al., 2003). Total triterpenes from C. asiatica

also ameliorated the function of hypothalamic-

pituitary-adrenal axis (HPA axis), increased the

contents of monoamine neurotransmitters in rat brain

and reduced the corticosterone level in serum (Chen et

al., 2005).

Antioxidant activity: C. asiatica possesses potent

antioxidant activity, which can exerted neuropro-

tective effect and effect against age related oxidative

damage in rats brain (Subathra et al., 2005). The

anti-oxidant enzymes, like superoxide dismutase

(SOD), catalase and glutathione peroxidase (GSHPx)

were significantly increased, and anti-oxidants like

glutathione (GSH) and ascorbic acid were decreased

in lymphoma-bearing mice after oral treatment with

50mg/kg of body weight per day of crude methanol

extract of C. asiatica for 14 days (Jayashree et al.,

2003). Administration of aqueous extracts of C.

asiatica showed to counteract lead-induced oxidative

stress male rats (Sainath et al., 2011). Flavonoid

compounds were present in aqueous extract of C.

asiatica, showed highest antioxidant property (Pittella

et al., 2009). The antioxidant properties of essential

oils and various extracts of this plant may be a great

interest in food industry, since their possible use as

natural additives. To study the antioxidant properties

and phenolic compounds present in C. asiatica, the

optimum brewing procedure was studied to use as

herbal teas (Ariffin et al., 2011).

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Antiulcer activity: C. asiatica showed significant

protection against ethanol, aspirin, cold restraint stress

and pyloric ligation induced gastric ulcers in rats when

200 mg/kg and 600 mg/kg of body weight of fresh

juice was given orally twice daily for five days

(Sairam et al., 2001). Water extract of C. asiatica

containing asiaticoside were found to reduce the size

of the acetic acid induced gastric ulcers in rats (Guo et

al., 2004).

Anxiolytic activity: 12 g oral single dose of C.

asiatica after 60 minutes significantly attenuated the

acoustic startle response (ASR) in human (Bradwejn

et al., 2000). The elevated plus maze (EPM) test for

5 minutes revealed that administration of standardized

extract, methanol and ethyl acetate extracts as well as

pure asiaticoside had imparted anxiolytic activity in

rats (Wijeweera et al., 2006; Wanasuntronwong et al.,

2012). Medication of 500 mg/capsule (concentrated

lyophilized of 70% hydro-ethanolic extract of C.

asiatica), twice daily, after meal for 60 days in 33

patient (18 male and 15 female; average age 33

years) in Kolkata (India) demonstrated that C.

asiatica not only significantly had attenuated

anxiety related disorders but it also significantly

had reduced stress phenomenon and its correlated

depression (Jana et al., 2010).

Cardioprotective activity: Administration of alcoholic

extract of C. asiatica at a dose of 1000 mg/kg of body

weight in Laboratory bred Sprague–Dawley rats

significantly reduced the necrosis of the myocardium

(Pragada et al., 2004). C. asiatica extract

demonstrated the cardioprotective effect at a dose of

200 mg/kg of body weight in adult male albino rats of

Wistar strain on antioxidant tissue defense system

during adriamycin induced cardiac damage (Gnana-

pragasam et al., 2004). Madecassoside showed protective

effect on myocardial ischemiareperfusion injury in

rabbits and rats (Li et al., 2007; Bian et al., 2008).

Hepatoprotective activity: Total glucosides extract of

C. asiatica showed significant anti-liver fibrosis effect

in dimethylnitrosamine induced liver fibrosis in rats

(Ming et al., 2004). Asiaticoside revealed hepatopro-

tective effect against acute liver injury induced by

lipopolysaccharide/D-galactosamine in mice (Zhang et

al., 2010).

Effect on Skin: Asiaticoside stimulated skin aging

inhibitor type 1 collagen synthesis in human dermal

fibroblast cells and potential use in the treatment

and/or prevention of hypertrophic scars and keloids

was recommended (Lee et al., 2006; Tang et al.,

2011b). Alcoholic extract of C. asiatica showed useful

effects in pruritis and other skin disease (Gohil et al.,

2010). Hydroalcoholic extract of C. asiatica was used

to be made herbal creams along with four medicinal

plants (Curcuma caesia, Areca catechu, Cinnamon

zeylanicum and Tamarindus indica) which showed

increased skin hydration, sebum levels, viscoelasticity,

and decreased melanin content (Saraf et al., 2012).

Asiaticoside promotes skin cell behaviours involved

in wound healing by increasing migration rates of skin

cells, enhancing the initial skin cell adhesion, inducing

an increase in the number of normal human dermal

fibroblasts (Lee et al., 2012). Aqueous extract of C.

asiatica was nano-encapsulated with gelatin and

efficiently reduced the expression of matrix

metalloproteinase (MMP)-1 in UV-irradiated cells and

inhibited hyaluronidase expression in mouse skin

(Kwon et al., 2012).

Immunomodulating activity: Triterpenoid saponins

of C. asiatica showed immunomodulatory effect

(Plohmann et al., 1997). Methanolic extract of C.

asiatica dramatically increased phagocytic index and

total WBC in Swiss Albino mice (Jayathirtha and

Mishra, 2004). Administration of water extract of C.

asiatica significantly increased proliferation and the

production of IL-2 and TNF-α in human peripheral

blood mononuclear cells (PBMCs) but ethanol extract

had inhibitory effect (Punturee et al., 2005). Asiatic

acid and C. asiatica ethanol and dichloromethane

extracts showed inhibitory effect on three major

cDNA, which expressed human cytochrome P450

(CYP2C9, CYP2D6 and CYP3A4) isoforms (Pan et

al., 2010).

Radioprotective activity: Aqueous extract C. asiatica

showed more radioprotective effect than standard drug

“ondansetron” against conditioned taste aversion

(behavioural perturbation) induced by 60Co-γ

irradiation at low dose 2Gy in male rats (Shobi and

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Goel, 2001). Administration of 100 mg/kg of body

weight of aqueous extract of C. asiatica, just 1 hour

before irradiation with 8Gy 60Co- γ rays was found

most radioprotective in Swiss Albino Mouse (Sharma

and Sharma, 2002) and further study revealed that

100mg/kg of body weight of dried powdered extract

of C. asiatica had found to be effective against

modified 60Co-γ irradiation induced damage in the

mouse liver (Sharma and Sharma, 2005). 70%

ethanolic extract of C. asiatica significantly reduced

radiation-induced damage to DNA (Joy and Nair,

2009). microRNA (miRNA) expression profiling

analysis was used to evaluate the protective effects of

C. asiatica against Ultraviolet B damage in human

keratinocytes, disclosed that miRNAs with altered

expression were functionally related with cell

proliferation and inhibition of apoptosis, may prevent

the skin damage (An et al., 2012).

Wound healing activity: A large number of reports

have been found about the wound healing activity of

C. asiatica (Temrangsee et al., 2011). Aqueous extract

of C. asiatica was used to formulate ointment, cream

and gel, which evaluate for wound healing in rats

showed faster epithelialisation and higher rate of

wound contraction (Sunilkumar et al., 1998).

Dexamethasone suppressed wound in Wistar Albino

rats could be healed by ethanolic leaf extracts as like

as normal model (Shetty et al., 2006). In a recent

study in 200 diabetic patients revealed positive result

with C. asiatica extracted capsule without any adverse

effect in the department of Surgery, Thammasat

University Hospital (Paocharoen, 2010). Wound

healing activity of asiaticoside was also reported in

guinea pig model at dose 1 mg/kg of body weight and

in the chick chorioallantoic membrane model at

concentration 40 µg/disk (Shukla et al., 1999). The

effects of asiaticoside in human periodontal ligament

cells (HPDLs) proliferation, protein synthesis, and

osteogenic differentiation were investigated and

showed enhanced periodontal tissue healing

(Nowwarote et al., 2012). At low concentrations

aqueous extract of C. asiatica promote epithelium

wound healing in rabbit corneal epithelial (RCE) cells

(Ruszymah et al., 2012). Ultra-fine cellulose acetate

fiber mats containing asiaticoside (in crude extract or

pure substance) were prepared and evaluated for

wound dressings and loaded herbal substances were

found stable up to 4 months, promotes proliferation

and upregulating the production of collagen of the

seeded (Suwantong et al., 2010). The clinical efficacy

and side effects of the oral C. asiatica extract capsule

in the diabetic wound healing was investigated

(Paocharoen, 2010). Madecassoside showed enhance

wound-healing and diminish keloid formation in

primary keloid-derived fibroblasts, originating from

human earlobe keloids (Song et al., 2012).

Memory enhancing Activity: Since the ancient time,

C. asiatica is used to enhance intelligence and

improve cognitive function. Oral administration with

200 mg/kg of body weight aqueous extract during

postnatal development stage increased brain function

in juvenile and young adult mice (Rao et al., 2005).

Enhanced working memory and improved self-rated

mood were observed in 28 patients after higher dose

administration of C. asiatiac extract preparations

(Wattanathorn et al., 2008). Asiatic acids isolated from

C. asiatica showed enhancing learning and memory

properties in male Spraque–Dawley rats (Nasir et al.,

2011b).

Burns: C. asiatica extract and its active constituents

are very effective against burns caused by boiling

water, electric current or gas exploitation.

Combination of C. asiatica extract with an antibiotic

was anti-infectious beside healing burns (Salas et al.,

2005). Low dose 10−8% to 10−12% (w/w) of

asiaticoside application facilitated repairing in mice

burned wound (Kimura et al., 2008).

Anti-psoriatic Activity: C. asiatica shows anti-

psoriatic effect on SVK-14 keratinocyte due to the

presence of triterpenoid glycosides (Sampson et al.,

2001).

Antimicrobial Activity: C. asiatica shows

antibacterial activity on both Gram positive and Gram

negative bacteria. Growth inhibition of Gram positive

Bacillus subtilis and Gram negative Pseudomonas

aeruginosa, P. cichorii and Escherichia coli was

observed in the disc diffusion test of hexane and ethyl

acetate extracts of C. asiatica (Escop and

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Phytotherapy, 2003). 1 000 µg/disc of hot methanolic

extract is moderately effective on Staphylococcus

aureus and Methicillin Resistant S. aureus (Wild Type)

(Zaidan et al., 2005). Micobacterium tuberculosis and

M. leprae were reported to be more sensitive to

liposomal asiatocoside than free asiatocoside (Fugh-

Berman, 2003). Higher antiviral activity was also

reported with aqueous extract of C. asiatica against

type 2 Herpes simplex virus (Escop and Phytotherapy,

2003).

Lervicidal Activity: Haemaphysalis bispinosa (the

adult cattle tick), Paramphistomum cervi (sheep fluke),

Anopheles subpictus and Culex tritaeniorhynchus

showed sensitivity to hexane, chloroform, ethyl

acetate, acetone, methanol extract of C. asiatica but

methanol extract was the most effective on P. cervi

and A. subpictus (Bagavan et al., 2009). 3-O-[a-L-

arabinopyranosyl] 2 a, 3 ß, 6 ß, 23-a tetrahydroxyurs-

12-ene-28-oic acid, a triterpenoid glycoside, exhibited

inhibitory activity against larvae of Spilarctia oblique

(Shukla et al., 2000).

Anti-hyperglycemic effect: Oral administration of

asiatic acid and glibenclamide to streptozotocin

induced diabetic rats for 45 days prevented the altered

activities of key enzymes (glucose-6-phosphatase and

fructose-1,6-bisphosphatase) related with hypergly-

cemia (Ramachandran and Saravanan, 2012).

Neuroprotective Activity: Aqueous extract showed

neuroprotective effect by increasing the antioxidant

enzyme level in mice corpus striatum and

hippocampus (Haleagrahara and Ponnusamy, 2010).

Fresh leaf extract of C. asiatica was investigated on

dendritic morphology of amygdaloid neurons on adult

rats, one of the regions concerned with learning and

memory, showed a significant increase in the dendritic

length and branching points (Rao et al., 2012). Water

extract of C. asiatica inhibit the activity of subtypes of

phospholipase A2 (PLA2), which is related with

neurodegenerative disease (Defillipo et al., 2012).

n-hexane, chloroform, ethyl acetate, n-butanol extract

of C. asiatica showed anticonvulsant and neuropro-

tective activity in male albino rats (Visweswari et al.,

2010). D-galactose induced oxidative and mitochon-

drial dysfunction and cognitive impairment in mice,

which could be significantly improved in six weeks by

administration of C. asiatica (150 and 300 mg/kg of

body weight) (Kumar et al., 2011). Chronic aluminum

exposure in rat induce cognitive dysfunction, apoptosis,

oxidative stress and mitochondrial enzyme alteration

and administration of C. asiatica found significantly

decreased aluminum concentration, improved memory

performance, oxidative defense, acetylcholinestrease

activity, caspase-3 and reversal of mitochondrial

enzyme activity as compared to control (Prakash and

Kumar, 2012). The psychoactive and antioxidant role

of ethanolic extract of C. asiatica in middle cerebral

artery occlusion (MCAO) in rats was evaluated and

revealed that administration of C. asiatica extract

restored histological morphology of brain, diminished

infarction volume, greatly improved the

neurobehavioral activity (Tabassum et al., 2012).

Asiatic acid possess neuroprotective effects in vitro

and in vivo (Xu et al., 2012b), nootropic activity with

therapeutic implications for patients with memory loss

(Shinomol et al., 2011). Increased dendritic length and

branches was observed in rat after fresh leaves extract

administration (Mohandas Rao et al., 2006). Three

derivatives of asiatic acid were significantly effective

in protecting excess glutamate exposed neurons on

cultured cortical cells (Lee et al., 2000; Xu et al.,

2012b). Non-polar fraction of ethanolic extract

containing asiatic acid which found to be increased in

neurite outgrowth in human SH-SY5Y cells in the

presence of nerve growth factor and administration of

ethanolic extract through drinking water demonstrated

axonal regeneration in Male Sprague-Dawley rats

(Soumyanath et al., 2005). Asiatic acid was reported

for the treatment of cerebral ischemia in mice

(Krishnamurthy et al., 2009). Asiatic acid showed

potential neuroprotective activity against

C2-ceramides-induced cell death in primary cultured

rat cortical neuronal cells (Zhang et al., 2012) and

asiaticoside significantly attenuated 1-methyl-4-

phenyl-1,2,3,6-tetrahydropyridine (MPTP) induce

Parkinsonism in rat model (Xu et al., 2012a).

Asiaticoside was recommended for epilepsy, stroke,

multiple sclerosis and other neuropsychiatric disorders

(Barbosa et al., 2008).

Venous insufficiency Activity: Patients suffering

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

from venous hypertension were positively effective to

an oral preparation of total triterpenic fraction of C.

asiatica (TTFCA) in the improvement of microcir-

culation and edema (leg volume) in venous

microangiopathy (Cesarone et al., 2001). C. asiatica

exract regulated mucopolysachharide metabolism in

connective tissue in patient with varicose veins

(Arpaia et al., 1990). However, a large number of

similar studies were reported on venous insufficiency.

Others: Asiaticoside was revealed as protective

against cecal ligation and puncture (CLP) induced

lung injury in mice (Zhang et al., 2010). This plant

also increases vigority (Mato et al., 2011). C. asiatica

extract in combination with Punica granatum

significantly improved clinical signs of chronic

periodontitis in 15 patients (Sastravaha et al., 2005).

Whole gene expression level were analyzed using

microarrays in human dermal fibroblasts (HDFs) to

determine whether H2O2 -induced senescence is

affected by C. asiatica extracts to characterized the

activity of extract in stress-induced premature

senescence (SIPS) and found that 39 mRNAs are

expressed differentially includes genes that regulate

cell growth, apoptosis, DNA replication, transcription,

gene silencing, senescence and the spindle checkpoint

(Kim et al., 2011). Oral administration of water extract

of C. asiatica protected the toxicity induced by

exogenously added and endogenously generated

β-amyloid in the Tg2576 mouse, which is a murine

model of Alzheimer’s disease with high β-amyloid

burden in SH-SY5Y cells and MC65 human

neuroblastoma cells from (Soumyanath et al., 2012).

Contradictions: Clinical study in patients suffering

from jaundice showed that all patients had improved

with C. asiatica discontinuation and deteriorated after

retaking due to having hepatotoxic effect (Jorge and

Jorge, 2005). This plant is not applicable for children,

pregnant and lactated women (Koh et al., 2009).

Traditional uses

Traditionally C. asiatica is used to treat differents

aliments in different countries for over a long time.

Traditional uses of C. asiatica are summarized in

Table 3.

In vitro propagation

Optimum shoots development of C. asiatica were

achieved in Duchefa medium supplemented with

2 mg/L 6 benzylaminopurine (BAP) and 0.1 mg/L

1-naphthaleneacetic acid (NAA) (Moghaddam et al.,

2011), Murashige and Skoog medium supplemented

with 2.5 mg/L kinetin (Prasad et al., 2012). Rooting

can be done on full-strength MS medium containing

0.5 mg/L indole-3-butyric acid (IBA) (Moghaddam et

al., 2011). Varying level of asiaticoside content in

shoot could be achieved with the varying ratio of

NH4+-N:NO3--N or Cu2+ concentration in the medium

(Prasad et al., 2012).

Conclusion

Since the time of immemorial C. asiatica is being

used for the treatment of wide range of maladies. So

far, the reports on bioactivity and clinical trials in

different models and human concern the asiaticoside

and its derivatives. Recent studies have confirmed the

efficacy of this plant and its constituents and extracts

to injury, leprosy, tuberculosis, cancer, aging,

gastrointestinal disease, skin disease, neurological

disorder, cardiovascular problems, ulcer, radiation,

respiratory problems and so on. However, further

clinical research are essential which can establish the

C. asiatica as a potential source of standard drugs.

Reference

An I.S., An S., Kang S.M., Choe T.B., Lee S.N., Jang H.H., and

Bae S., 2012, Titrated extract of Centella asiatica provides

a UVB protective effect by altering microRNA expression

profiles in human dermal fibroblasts, International Journal

of Molecular Medicine, 30: 1194–1202

Antognoni F., Perellino N.C., Crippa S., Dal Toso R., Danieli

B., Minghetti A., Poli F., and Pressi G., 2011, Irbic acid, a

dicaffeoylquinic acid derivative from Centella asiatica

cell cultures, Fitoterapia, 82: 950-954, http://dx.doi.org/10.

1016/ j.fitote. 2011.05.008

Ariffin F., Heong Chew S., Bhupinder K., Karim A.A., and

Huda N., 2011, Antioxidant capacity and phenolic

composition of fermented Centella asiatica herbal teas,

Journal of the Science of Food and Agriculture, 91:

2731-2739, http://dx.doi.org/10.1002/jsfa.4454

Arpaia M.R., Ferrone R., Amitrano M., Nappo C., Leonardo G.,

and Del Guercio R., 1990, Effects of Centella asiatica

extract on mucopolysaccharide metabolism in subjects

with varicose veins, International Journal of Clinical

Pharmacology Research, 10: 229–233

Medicinal Plant Research 2013, Vol.3, No.4, 20

http://mpr.sophiapublisher.com

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,

dysentery, vomiting, red eyes, swollen throat, tonsillitis, nosebleeds, jaundice, infectious

hepatitis, boils, fistulas, furuncles and carbuncles with toxic swelling, fever, trauma, falls,

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

(Leonard,

2006; Koh et

al., 2009)

Europe

Varicose veins

(Leonard,

2006)

Fiji

Skin ulcers, rash, and redness, pimples, stomachache, bleeding ulcer, constipation, hemorroids,

eye problems, fractures, painful and swollen joints, rib pain, hildhood convulsions, post partum

weakness, unwanted pregnancy

(Leonard,

2006)

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,

cholera, abdominal tumor, anxiety neurosis, insanity, poor memory, general debility, blood

disease

(Leonard,

2006; Koh et

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

disease, leprosy

(Leonard,

2006)

Tonga

Juiced for eye ailments and nasally for migraines, convulsions, delayed closure of the fonatel,

navel infection in babies

(Leonard,

2006)

Turkey

Spasms, leprosy

(Leonard,

2006)

Babykutty S., Padikkala J., Sathiadevan P.P., Vijayakurup V.,

Az i s T.K.A., Srinivas P., and Gopala S., 2009, Apoptosis

induction of Centella asiatica on human breast cancer

cells, Afr. J. Trad. CAM, 6: 9–16

Bagavan A., Kamaraj C., Elango G., Abduz Zahir a, and Abdul

Rahuman a., 2009, Adulticidal and larvicidal efficacy of

some medicinal plant extracts against tick, fluke and

mosquitoes, Veterinary Parasitology, 166: 286–292, http://

dx. doi.org/10.1016/j.vetpar.2009.09.007

Barbosa N.R., Pittella F., and Gattaz W.F., 2008, Centella

asiatica water extract inhibits iPLA2 and cPLA2 activities

in rat cerebellum, Phytomedicine: International Journal of

Phytotherapy and Phytopharmacology, 15: 896-900,

http://dx.doi.org/10.1016/j.phymed.2008.02.007

Barnes J., Anderson L.A., and Phillipson J.D., 2007, Herbal

Medicines, London, UK: Published by the Pharmaceutical

Press, RPS Publishing

Belcaro G., Maquart F.X., Scoccianti M., Dugall M., Hosoi M.,

Cesarone M.R., Luzzi, R., Cornelli U., Ledda A., and

Feragalli B., 2011, TECA (Titrated Extract of Centella

asiatica): new microcirculatory, biomolecular, and

vascular application in preventive and clinical medicine. A

status paper, Panminerva Medica 53: 105–118.

Bhandari P., Kumar N., Gupta A.P., Singh B., and Kaul V.K.,

2007, A rapid RP-HPTLC densitometry method for

simultaneous determination of major flavonoids in

important medicinal plants, Journal of Separation Science,

30: 2092–2096, http://dx.doi.org/10.1002/jssc.200700066

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Bian D., Liu M., Li Y., Xia Y., Gong Z., and Dai Y., 2012,

Madecassoside, a triterpenoid saponin isolated from

Centella asiatica herbs, protects endothelial cells against

oxidative stress, Journal of Biochemical and Molecular

Toxicology 26: 399–406, http://dx.doi.org/10.1002/

jbt.21434

Bian G.X., Li G.G., Yang Y., Liu R.T., Ren J.P., Wen L.Q., Guo

S.M., and Lu Q.J., 2008, Madecassoside reduces

ischemia-reperfusion injury on regional ischemia induced

heart infarction in rat, Biological & Pharmaceutical

Bulletin, 31: 458–463, http://dx.doi.org/10.1248/bpb.31.

458

Bradwejn J., Zhou Y., Koszycki D., and Shlik J., 2000, A

double-blind, placebo-controlled study on the effects of

Gotu Kola (Centella asiatica) on acoustic startle response

in healthy subjects, Journal of Clinical

Psychopharmacology, 20: 680–684, http://dx.doi.org/

10.1097/00004714-200012000-00015

Bunpo P., Kataoka K., Arimochi H., Nakayama H., Kuwahara

T., Bando Y., Izumi K., Vinitketkumnuen U., and Ohnishi

Y., 2004, Inhibitory effects of Centella asiatica on

azoxymethane-induced aberrant crypt focus formation and

carcinogenesis in the intestines of F344 rats, Food and

Chemical Toxicology: An International Journal Published

for the British Industrial Biological Research Association,

42: 1987–1997, http://dx.doi.org/10.1016/j.fct.2004.06.

022

Cesarone M.R., Belcaro G., De Sanctis M.T., Incandela L.,

Cacchio M., Bavera P., Ippolito E., Bucci M., Griffin M.,

and Geroulakos G., 2001, Effects of the total triterpenic

fraction of Centella asiatica in venous hypertensive

microangiopathy: a prospective, placebo-controlled,

randomized trial, Angiology, 52 Suppl 2S: 15–18

Chauhan N.S., 1999, Medicinal and Aromatic Plants of

Himachal Pradesh (New Dehli India: Gidwani Indus

Publishing)

Chen Y., Han T., Qin L., Rui Y., and Zheng H., 2003, Effect of

total triterpenes from Centella asiatica on the depression

behavior and concentration of amino acid in forced

swimming mice, Journal of Chinese Medicinal Materials,

26: 870–873

Chen Y., Han T., Rui Y., Yin M., Qin L., and Zheng H., 2005,

Effects of total triterpenes of Centella asiatica on the

corticosterone levels in serum and contents of monoamine

in depression rat brain, Journal of Chinese Medicinal

Materials, 28: 492–496

Chevallier A., 2001, Encyclopedia of Medicinal Plants (Natural

Care) (Dorling Kindersley Publishing Australia Chong

N.J., and Aziz Z., 2011, A systematic review on the

chemical constituents of Centella asiatica. Research

Journal of Pharmaceutical, Biological and Chemical

Sciences, 2: 445–459

Craker L.E., and Simon J.E., 1986, Herbs, Spices, and

Medicinal Plants: Recent Advances in Botany,

Horticulture, and Pharmacology, Volume 1 (Routledge)

Defillipo P.P., Raposo A.H., Fedoce A.G., Ferreira A.S.,

Polonini H.C., Gattaz W.F., and Raposo N.R.B., 2012,

Inhibition of cPLA2 and sPLA2 activities in primary

cultures of rat cortical neurons by Centella asiatica water

extract, Natural Product Communications, 7: 841–843

Escop, and Phytotherapy, E.S.C., 2003, Escop monographs: the

scientific foundation for herbal medicinal products,

Thieme

Fugh-Berman A., 2003, 5-minute herb & dietary supplement

consult (Lippincott Williams & Wilkins)

George M., Joseph L., and Ramaswamy, 2009, Anti -allergic,

Anti-pruritic, and anti-inflammatory activitues of Centella

asiatica extracts, Afr. J. Trad. CAM, 6: 54–559

Gnanapragasam a, Ebenezar K.K., Sathish V., Govindaraju P.,

and Devaki T., 2004, Protective effect of Centella asiatica

on antioxidant tissue defense system against adriamycin

induced cardiomyopathy in rats, Life Sciences, 76:

585–597, http://dx.doi.org/10.1016/j.lfs.2004.09.009

Gohil K.J., Patel J.A., and Gajjar A.K., 2010, Pharmacological

Review on Centella asiatica: A Potential Herbal Cure-all.

Indian Journal of Pharmaceutical Sciences, 72: 546–556,

http://dx.doi.org/10.4103/0250-474X.78519

Goldstein M.C., and Goldstein M.A., 2012, Healthy Herbs:

Fact Versus Fiction, Greenwood, UK

Guo F.F., Feng X., Chu Z.Y., Li D.P., Zhang L., and Zhang Z.S.,

2012, Microbial transformation of asiatic acid. Journal of

Asian Natural Products Research, 1–7, http://dx.doi.org/

10.1080/10286020.2012.741124

Guo J.S., Cheng C.L., and Koo M.W.L., 2004, Inhibitory

effects of Centella asiatica water extract and asiaticoside

on inducible nitric oxide synthase during gastric ulcer

healing in rats. Planta Medica, 70: 1150–1154,

http://dx.doi.org/10.1055/s-2004-835843

Haleagrahara N., and Ponnusamy K., 2010, Neuroprotective

effect of Centella asiatica extract (CAE) on

experimentally induced parkinsonism in aged

Sprague-Dawley rats, The Journal of Toxicological

Sciences, 35: 41–47, http://dx. doi.org/10.2131/jts.35.41

Han W.J., Xia Y.F., and Dai Y., 2012, Development and

validation of high-performance liquid chromatography/

electrospray ionization mass spectrometry for assay of

madecassoside in rat plasma and its application to

pharmacokinetic study, Biomedical Chromatography:

BMC, 26: 26–32, http://dx.doi.org/10.1002/bmc.1620

Huang S.S., Chiu C.S., Chen H.J., Hou W.C., Sheu M.J., Lin

Y.C., Shie P.H., and Huang G.J., 2011, Antinociceptive

activities and the mechanisms of anti-inflammation of

asiatic Acid in mice. Evidence-based Complementary and

Alternative Medicine: eCAM 2011, 895857.

Huang Y.H., Zhang S.H., Zhen R.X., Xu X.D., and Zhen Y.S.,

2004, Asiaticoside inducing apoptosis of tumor cells and

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

enhancing anti-tumor activity of vincristine, Chinese

Journal of Cancer, 23: 1599–1604

Jamil S.S., Nizami Q., Salam M., and Urban L., 2007, Centella

asiatica L. Urban óA Review. Nature Product Radiance, 6:

158–170

Jana U., Sur T.K., Maity L.N., Debnath P.K., and

Bhattacharyya D., 2010, A clinical study on the

management of generalized anxiety disorder with Centella

asiatica, Nepal Medical College Journal: NMCJ, 12: 8–11

Jayashree G., Kurup Muraleedhara G., Sudarslal S., and Jacob

V.B., 2003, Anti-oxidant activity of Centella asiatica on

lymphoma-bearing mice, Fitoterapia, 74: 431–434, http://

dx.doi.org/10.1016/S0367-326X(03)00121-7

Jayathirtha M.G., and Mishra S.H., 2004, Preliminary

immunomodulatory activities of methanol extracts of

Eclipta alba and Centella asiatica, Phytomedicine:

International Journal of Phytotherapy and

Phytopharmacology, 11: 361–365, http://dx.doi.org/

10.1078/ 0944711041495236

Jorge O.A., and Jorge A.D., 2005, Hepatotoxicity associated

with the ingestion of Centella asiatica, Revista Española

De Enfermedades Digestivas: Organo Oficial De La

Sociedad Española De Patología Digestiva, 97: 115–124

Joy J., and Nair C.K.K., 2009, Protection of DNA and

membranes from gamma-radiation induced damages by

Centella asiatica, The Journal of Pharmacy and

Pharmacology, 61: 941–947

Joy P.P., Thomas J., Varghese C.S., Indumon S.S., and George

D., 1998, Medicinal Plants (Kerala Agricultural University,

Kerala, India)

Juengwatanatrakul T., Sritularak B., Amornnopparattanakul P.,

Tassanawat P., Putalun W., Tanaka H., and Morimoto S.,

2011, Preparation of a specific monoclonal antibody to

asiaticoside for the development of an enzyme-linked

immunosorbent assay, The Analyst, 136: 1013–1017,

http://dx.doi.org/10.1039/c0an00868k

Kim Y.J., Cha H.J., Nam K.H., Yoon Y., Lee H., and An S.,

2011, Centella asiatica extracts modulate hydrogen

peroxide-induced senescence in human dermal fibroblasts,

Experimental Dermatology, 20: 998–1003, http://dx.

doi.org/10.1111/j.1600-0625.2011.01388.x

Kimura Y., Sumiyoshi M., Samukawa K.I., Satake N., and

Sakanaka M., 2008, Facilitating action of asiaticoside at

low doses on burn wound repair and its mechanism,

European Journal of Pharmacology, 584: 415–423,

http://dx.doi.org/10.1016/j.ejphar.2008.02.036

Koh H.L., Chua T.K., and Tan C.H., 2009, A guide to medicinal

plants: an illustrated, scientific and medicinal approach

(Hackensack, NJ 07601 USA: World Scientific Publishing

Co Pte Ltd)

Krishnamurthy R.G., Senut M.C., Zemke D., Min J., Frenkel

M.B., Greenberg E.J., Yu S.-W., Ahn N., Goudreau J., and

Kassab M., 2009, Asiatic acid, a pentacyclic triterpene

from Centella asiatica, is neuroprotective in a mouse

model of focal cerebral ischemia, Journal of Neuroscience

Research, 87: 2541–2550, http://dx.doi.org/10.1002/

jnr.22071

Kumar A., Prakash A., and Dogra S., 2011, Centella asiatica

attenuates d-galactose-induced cognitive impairment,

Oxidative and Mitochondrial Dysfunction in Mice,

International Journal of Alzheimer's Disease, 347569

Kwon M.C., Choi W.Y., Seo Y.C., Kim J.S., Yoon C.S., Lim

H.W., Kim H.S., Ahn J.H., and Lee H.Y., 2012,

Enhancement of the skin-protective activities of Centella

asiatica L. Urban by a nano-encapsulation process,

Journal of Biotechnology, 157: 100–106, http://dx.doi.org/

10.1016/ j.jbiotec.2011.08.025

Lee J., Jung E., Kim Y., Park J., Park J., Hong S., Kim J., Hyun

C., Kim Y.S., and Park D., 2006, Asiaticoside induces

human collagen I synthesis through TGFbeta receptor I

kinase (TbetaRI kinase)-independent Smad signaling.,

Planta Medica, 72: 324–328, http://dx.doi.org/10.1055/

s-2005-916227

Lee J.H., Kim H.L., Lee M.H., You K.E., Kwon B.J., Seo H.J.,

and Park J.C., 2012, Asiaticoside enhances normal human

skin cell migration, attachment and growth in vitro wound

healing model, Phytomedicine: International Journal of

Phytotherapy and Phytopharmacology, 19: 1223–1227,

http://dx.doi.org/10.1016/j.phymed.2012.08.002

Lee M.K., Kim S.R., Sung S.H., Lim D., Kim H., Choi H., Park

H.K., Je S., and Ki Y.C., 2000, Asiatic acid derivatives

protect cultured cortical neurons from glutamate-induced

excitotoxicity, Research Communications in Molecular

Pathology and Pharmacology, 108: 75–86

Leonard D.B., 2006, Medicine at your feet: healing plants of

the hawaiian kingdom Centella asiatica (Pohe kula)

(Roast Duck Producktion)

Li G.G., Bian G.X., Ren J.P., Wen L.Q., Zhang M., and Lü Q.J.,

2007, Protective effect of madecassoside against

reperfusion injury after regional ischemia in rabbit heart in

vivo, Acta Pharmaceutica Sinica, 42: 475–480

Liu M., Dai Y., Yao X., Li Y., Luo Y., Xia Y., and Gong Z.,

2008, Anti-rheumatoid arthritic effect of madecassoside on

type II collagen-induced arthritis in mice, International

Immunopharmacology, 8: 1561–1566, http://dx.doi.org/

10.1016/ j.intimp.2008.06.011

Mato L., Wattanathorn J., Muchimapura S., Tongun T.,

Piyawatkul N., Yimtae K., Thanawirattananit P., and

Sripanidkulchai B., 2011, Centella asiatica improves

physical performance and health-related quality of life in

healthy elderly volunteer, Evidence-based Complementary

and Alternative Medicine: eCAM 2011, 579467

Meulenbeld G.J., and Wujastyk D., 2001, Studies on indian

medical history this is a scholarly work. the historical

narrative is most interesting, The Scientific And Medical

Network (New Dehli: Motilal Banarsidass Publ Ming Z.,

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

Liu S., and Cao L., 2004, Effect of total glucosides of

Centella asiatica on antagonizing liver fibrosis induced by

dimethylnitrosamine in rats, Chinese Journal of Integrated

Traditional and Western Medicine, 24: 731–734

Moghaddam S.S., Jaafar, H.B., Aziz M.A., Ibrahim R.., Rahmat

A.B., and Philip E., 2011, Optimization of an efficient

semi-solid culture protocol for sterilization and plant

regeneration of Centella asiatica (L.) as a medicinal herb.

Molecules (Basel, Switzerland) 16, 8981-8991,

http://dx.doi.org/10.3390/molecules16118981

Mohandas Rao, K.G., Muddanna Rao, S., and Gurumadhva Rao,

S., 2006, Centella asiatica (L.) leaf extract treatment

during the growth spurt period enhances hippocampal

CA3 neuronal dendritic arborization in rats.

Evidence-based Complementary and Alternative Medicine:

eCAM 3, 349–357.

Nasir M.N., Abdullah J., Habsah M., Ghani R.I., and Rammes

G., 2012, Inhibitory effect of asiatic acid on acetylcho

linesterase, excitatory post synaptic potential and

locomotor activity. Phytomedicine: International Journal

of Phytotherapy and Phytopharmacology, 19:311-316,

http://dx.doi.org/10.1016/j.phymed.2011.10.004

Nasir M.N., Habsah M., Zamzuri I., Rammes G., Hasnan J., and

Abdullah J., 2011a, Effects of asiatic acid on passive and

active avoidance task in male Spraque-Dawley rats,

Journal of Ethnopharmacology, 134: 203-209, http://dx.

doi. org/ 10.1016/j.jep.2010.12.010

Nasir M.N., Habsah M., Zamzuri I., Rammes G., Hasnan J., and

Abdullah J., 2011b, Effects of asiatic acid on passive and

active avoidance task in male Spraque-Dawley rats,

Journal of Ethnopharmacology, 134: 203–209, http://dx.

doi. org/10.1016/j.jep.2010.12.010

Nhiem N.X., Tai B.H., Quang T.H., Kiem P.V., Minh C.V., Nam

N.H., Kim J.H., Im L.R., Lee Y.M., and Kim Y.H., 2011, A

new ursane-type triterpenoid glycoside from Centella

asiatica leaves modulates the production of nitric oxide

and secretion of TNF-α in activated RAW 264.7 cells,

Bioorganic & Medicinal Chemistry Letters, 21: 1777-1781,

http://dx.doi.org/10.1016/j.bmcl.2011.01.066

Nowwarote N., Osathanon T., Jitjaturunt P., Manopattana-

soontorn S., and Pavasant P., 2012, Asiaticoside induces

type I collagen synthesis and osteogenic differentiation in

human periodontal ligament cells, Phytotherapy Research:

PTR

Pan Y., Abd-Rashid B.A., Ismail Z., Ismail R., Mak J.W., Pook

P.C.K., Er H.M., and Ong C.E., 2010, In vitro modulatory

effects on three major human cytochrome P450 enzymes

by multiple active constituents and extracts of Centella

asiatica, Journal of Ethnopharmacology, 130: 275-283,

http://dx.doi.org/10.1016/j.jep.2010.05.002

Paocharoen V., 2010, The efficacy and side effects of oral

Centella asiatica extract for wound healing promotion in

diabetic wound patients, Journal of the Medical

Association of Thailand = Chotmaihet Thangphaet, 93

Suppl 7: S166-70

Di Paola R., Esposito E., Mazzon E., Caminiti R., Toso R.D.,

Pressi G., and Cozzocrea S., 2010, 3,5-Dicaffeoyl-

4-malonylquinic acid reduced oxidative stress and

inflammation in a experimental model of inflammatory

bowel disease, Free Radical Research, 44: 74–89,

http://dx.doi.org/10.3109/10715760903300709

Paolino D., Cosco D., Cilurzo F., Trapasso E., Morittu V.M.,

Celia C., and Fresta M., 2012, Improved in vitro and in

vivo collagen biosynthesis by asiaticoside-loaded

ultradeformable vesicles, Journal of Controlled Release:

Official Journal of the Controlled Release Society, 162:

143-151, http://dx.doi.org/10.1016/j.jconrel.2012.05.050

Park B.C., Bosire K.O., Lee E.S., Lee Y.S., and Kim J.A., 2005,

Asiatic acid induces apoptosis in SK-MEL-2 human

melanoma cells, Cancer Letters, 218: 81-90, http://dx.

doi.org/10.1016/j.canlet.2004.06.039

Pittella F., Dutra R.C., Junior D.D., Lopes M.T.P., and Barbosa

N.R., 2009, Antioxidant and cytotoxic activities of

Centella asiatica (L) Urb, International Journal of

Molecular Sciences, 10: 3713–3721, http://dx.doi.org/

10.3390/ijms10093713

Plohmann B., Bader G., Hiller K., and Franz G., 1997,

Immunomodulatory and antitumoral effects of triterpenoid

saponins, Die Pharmazie, 52: 953-957

Pragada R.R., Veeravalli K.K., Chowdary K.P.R., and Routhu

K.V., 2004, Cardioprotective activity of Hydrocotyle

asiatica L. in ischemia-reperfusion induced myocardial

infarction in rats, Journal of Ethnopharmacology, 93:

105–108, http://dx.doi.org/10.1016/j.jep.2004.03.025

Prakash A., and Kumar A., 2012, Mitoprotective effect of

Centella asiatica against aluminum-induced neurotoxicity

in rats: possible relevance to its anti-oxidant and

anti-apoptosis mechanism, Neurological Sciences: Official

Journal of the Italian Neurological Society and of the

Italian Society of Clinical Neurophysiology

Prasad A., Mathur A., Singh M., Gupta M.M., Uniyal G.C., Lal

R.K., and Mathur A.K., 2012, Growth and asiaticoside

production in multiple shoot cultures of a medicinal herb,

Centella asiatica (L.) Urban, under the influence of

nutrient manipulations, Journal of Natural Medicines, 66:

383-387, http://dx.doi.org/10.1007/s11418-011-0588-9

Punturee K., Wild C.P., Kasinrerk W., and Vinitketkumnuen U.,

2005, Immunomodulatory activities of Centella asiatica

and Rhinacanthus nasutus extracts, Asian Pacific Journal

of Cancer Prevention: APJCP, 6: 396-400

Puttarak P., and Panichayupakaranant P., 2012a, A new method

for preparing pentacyclic triterpene rich Centella asiatica

extracts, Natural Product Research, http://dx.doi.org/

10.1080/14786419.2012.686912

Puttarak P., and Panichayupakaranant P., 2012b, Factors

affecting the content of pentacyclic triterpenes in Centella

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

asiatica raw materials, Pharmaceutical Biology, 50:

1508–1512,http://dx.doi.org/10.3109/13880209.2012.6859

Ramachandran V., and Saravanan R., 2012, Efficacy of asiatic

acid, a pentacyclic triterpene on attenuating the key

enzymes activities of carbohydrate metabolism in

streptozotocin-induced diabetic rats, Phytomedicine:

International Journal of Phytotherapy and Phytoph-

armacology

Rao K.G.M., Rao M.S., and Rao G.S., 2012, Evaluation of

amygdaloid neuronal dendritic arborization enhancing

effect of Centella asiatica (Linn) fresh leaf extract in adult

rats, Chinese Journal of Integrative Medicine epub ahead,

1–6

Rao S.B., Chetana M., and Uma Devi P., 2005, Centella

asiatica treatment during postnatal period enhances

learning and memory in mice, Physiology & Behavior, 86:

449-457, http://dx.doi.org/10.1016/j.physbeh.2005.07.019

Ruszymah B.H.I., Chowdhury S.R., Manan N.A.B.A., Fong

O.S., Adenan M.I., and Saim A. Bin 2012, Aqueous

extract of Centella asiatica promotes corneal epithelium

wound healing in vitro, Journal of Ethnopharmacology,

140: 333-338

Sainath S.B., Meena R., Supriya C., Reddy K.P., and Reddy

P.S., 2011, Protective role of Centella asiatica on

lead-induced oxidative stress and suppressed reproductive

health in male rats, Environmental Toxicology and

Pharmacology, 32: 146-154, http://dx.doi.org/10.1016/

j.etap. 2011.04.005

Sairam K., Rao C. V, and Goel R.K., 2001, Effect of Centella

asiatica Linn on physical and chemical factors induced

gastric ulceration and secretion in rats, Indian Journal of

Experimental Biology, 39: 137-142

Salas C.L., Fernándes M.M., and Ana M.M. de la C., 2005,

Topical chemotherapy for the treatment of burns, Revista

De Enfermería (Barcelona, Spain), 28: 67-70

Sampson J.H., Raman, A., Karlsen, G., Navsaria, H., and Leigh

I.M., 2001, In vitro keratinocyte antiproliferant effect of

Centella asiatica extract and triterpenoid saponins,

Phytomedicine: International Journal of Phytotherapy and

Phytopharmacology, 8: 230-235, http://dx.doi.org/10.10

78/0944-7113-00032

Saraf S., Chhabra S.K., Kaur C.D., and Saraf S., 2012,

Development of photochemoprotective herbs containing

cosmetic formulations for improving skin properties,

Journal of Cosmetic Science, 63: 119-131

Sastravaha G., Gassmann G., Sangtherapitikul P., and 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: 70-79

Sharma J., and Sharma R., 2002, Radioprotection of Swiss

albino mouse by Centella asiatica extract, Phytotherapy

Research: PTR, 16: 785-786

Sharma R., and Sharma J., 2005, Modification of gamma ray

induced changes in the mouse hepatocytes by Centella

asiatica extract: in vivo studies, Phytotherapy Research:

PTR 19: 05–611

Shetty B.S., Udupa S.L., Udupa L., and Somayaji S.N., 2006,

Effect of Centella asiatica L (Umbelliferae) on normal

and dexamethasone-suppressed wound healing in Wistar

Albino rats. The International Journal of Lower Extremity

Wounds 5, 137-143, http://dx.doi.org/10.1177/153473

4606291313

Shinomol G.K., Muralidhara, and Bharath M.M.S., 2011,

Exploring the role of "Brahmi" (Bocopa monnieri and

Centella asiatica) in brain function and therapy, Recent

Patents on Endocrine, Metabolic & Immune Drug

Discovery, 5: 33-49

Shobi V., and Goel H.C., 2001, Protection against

radiation-induced conditioned taste aversion by Centella

asiatica, Physiology & Behavior, 73: 19-23, http://

dx.doi.org/10.1016/S0031-9384(01)00434-6

Shukla A, Rasik A.M., and Dhawan B.N., 1999,

Asiaticoside-induced elevation of antioxidant levels in

healing wounds, Phytotherapy Research: PTR 13: 50-54

Shukla Y.N., Srivastava R., Tripathi a K., and Prajapati V., 2000,

Characterization of an ursane triterpenoid from centella

asiatica with growth inhibitory activity against spilarctia

oblique, Pharmaceutical Biology, 38: 262–267

Singh S., Gautam A., Sharma A., and Batra A., 2010, Centella

asiatica L.: A plant with immense medicinal but

threatened, 4: 9–17

Song J., Xu H., Lu Q., Xu Z., Bian D., Xia Y., Wei Z., Gong Z.,

and Dai Y., 2012, Madecassoside suppresses migration of

fibroblasts from keloids: involvement of p38 kinase and

PI3K signaling pathways, Burns: Journal of the

International Society for Burn Injuries, 38: 677–684,

http://dx.doi.org/10.1016/j.burns.2011.12.017

Soumyanath A., Zhong Y.P., Gold S. a, Yu X., Koop D.R.,

Bourdette D., and Gold B.G., 2005, Centella asiatica

accelerates nerve regeneration upon oral administration

and contains multiple active fractions increasing neurite

elongation in-vitro, The Journal of Pharmacy and

Pharmacology, 57: 1221-1229, http://dx.doi.org/10.1211/

jpp.57.9.0018

Soumyanath A., Zhong Y.P., Henson E., Wadsworth T., Bishop

J., Gold B.G., and Quinn J.F., 2012, Centella asiatica

extract improves behavioral deficits in a mouse model of

alzheimer's disease: investigation of a possible mechanism

of action, International Journal of Alzheimer's Disease,

381974

Subathra M., Shila S., Devi M.A., and Panneerselvam C., 2005,

Emerging role of Centella asiatica in improving

age-related neurological antioxidant status, Experimental

Gerontology, 40: 707-715, http://dx.doi.org/10.1016/

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

j.exger.2005.06.001

Sunilkumar, Parameshwaraiah S., and Shivakumar H.G., 1998,

Evaluation of topical formulations of aqueous extract of

Centella asiatica on open wounds in rats. Indian Journal

of Experimental Biology, 36: 569-572

Suwantong O., Ruktanonchai U., and Supaphol P., 2010, In

vitro biological evaluation of electrospun cellulose acetate

fiber mats containing asiaticoside or curcumin, Journal of

Biomedical Materials Research, Part A, 94: 1216–1225.

Tabassum R., Vaibhav K., Shrivastava P., Khan A., Ejaz Ahmed

M., Javed H., Islam F., Ahmad S., Saeed Siddiqui M., and

Safhi M.M., 2012, Centella asiatica attenuates the

neurobehavioral, neurochemical and histological changes

in transient focal middle cerebral artery occlusion rats,

Neurological Sciences: Official Journal of the Italian

Neurological Society and of the Italian Society of Clinical

Neurophysiology

Tang B., Zhu B., Liang Y., Bi L., Hu Z., Chen B., Zhang K.,

and Zhu J., 2011a, Asiaticoside suppresses collagen

expression and TGF-β/Smad signaling through inducing

Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid

fibroblasts, Archives of Dermatological Research, 303:

563-572, http://dx.doi.org/10.1007/s00403-010-1114-8

Tang B., Zhu B., Liang Y., Bi L., Hu Z., Chen B., Zhang K.,

and Zhu J., 2011b, Asiaticoside suppresses collagen

expression and TGF-β/Smad signaling through inducing

Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid

fibroblasts, Archives of Dermatological Research 303:

563-572, http://dx.doi.org/10.1007/s00403-010-1114-8

Tang X.L., Yang X.Y., Jung H.J., Kim S.Y., Jung S.Y., Choi

D.Y., Park W.C., and Park H., 2009, Asiatic acid induces

colon cancer cell growth inhibition and apoptosis through

mitochondrial death cascade, Biological & Pharmaceutical

Bulletin, 32: 1399-1405, http://dx.doi.org/10.1248/

bpb.32.1399

Tassanawat P., Putalun W., Yusakul G., Sritularak B.,

Juengwatanatrakul T., and Tanaka H., 2012, Production of

polyclonal antibody against madecassoside and

development of immunoassay methods for analysis of

triterpene glycosides in Centella asiatica, Phytochemical

Analysis: PCA, doi: 10.1002/pca.2406, http://dx.doi.org/

10.1002/pca.2406

Temrangsee P., Kondo S., and Itharat A., 2011, Antibacterial

activity of extracts from five medicinal plants and their

formula against bacteria that cause chronic wound

infection, Chotmaihet Thangphaet, 94 Suppl 7S: 166–71

Visweswari G., Prasad K.S., Chetan P.S., Lokanatha V., and

Rajendra W., 2010, Evaluation of the anticonvulsant effect

of Centella asiatica (gotu kola) in pentylene tetrazol-

induced seizures with respect to cholinergic neurotran-

smission, Epilepsy & Behavior: E&B, 17: 332-335

Wan J., Gong X., Jiang R., Zhang Z., and Zhang L., 2012,

Antipyretic and anti-inflammatory effects of asiaticoside

in lipopolysaccharide-treated rat through up-regulation of

heme oxygenase-1, Phytotherapy Research, PTR

Wanasuntronwong A., Tantisira M.H., Tantisira B., and

Watanabe H., 2012, Anxiolytic effects of standardized

extract of Centella asiatica (ECa 233) after chronic

immobilization stress in mice, Journal of Ethnoph-

armacology, 143: 579-585, http://dx.doi.org/10.1016/

j.jep.2012.07.010

Wattanathorn J., Mator, L., Muchimapura S., Tongun T.,

Pasuriwong O., Piyawatkul N., Yimtae K., Sripanidkulchai

B., and Singkhoraard J., 2008, Positive modulation of

cognition and mood in the healthy elderly volunteer

following the administration of Centella asiatica. Journal

of Ethnopharmacology, 116: 325–332, http://dx.doi.org/

10.1016/j.jep.2007.11.038

Weng X.X., Shao Y., Chen Y.Y., Gao W., Cheng L., and Kong

D.Y., 2011, Two new dammarane monodesmosides from

Centella asiatica, Journal of Asian Natural Products

Research, 13: 749–755, http://dx.doi.org/10.1080/10286

020.2011.588212

Wijeweera P., Arnason J.T., Koszycki D., and Merali Z., 2006,

Evaluation of anxiolytic properties of Gotukola--(Centella

asiatica) extracts and asiaticoside in rat behavioral models,

Phytomedicine: International Journal of Phytotherapy and

Phytopharmacology, 13: 668–676, http://dx.doi.org/

10.1016/j.phymed.2006.01.011

Won J.H., Shin J.S., Park H.J., Jung H.J., Koh D.J., Jo B.G.,

Lee J.Y., Yun K., and Lee K.T., 2010, Anti-inflammatory

effects of madecassic acid via the suppression of

NF-kappaB pathway in LPS-induced RAW 264.7

macrophage cells, Planta Medica: 76, 251–257,

http://dx.doi.org/10.1055/s-0029-1186142

Xu C.L., Wang Q.Z., Sun L.M., Li X.M., Deng J.M., Li L.F.,

Zhang J., Xu R., and Ma S.P., 2012a, Asiaticoside:

attenuation of neurotoxicity induced by MPTP in a rat

model of Parkinsonism via maintaining redox balance and

up-regulating the ratio of Bcl-2/Bax. Pharmacology,

Biochemistry, and Behavior,100: 413–418, http://dx.

doi.org/10.1016/j.pbb.2011.09.014

Xu M., Xiong Y., Liu J., Qian J., Zhu L., and Gao J., 2012b,

Asiatic acid, a pentacyclic triterpene in Centella asiatica,

attenuates glutamate-induced cognitive deficits in mice

and apoptosis in SH-SY5Y cells, Acta Pharmacologica

Sinica, 33: 578–587, http://dx.doi.org/10.1038/aps.2012.3

Yoshida M., Fuchigami M., Nagao T., Okabe H., Matsunaga K.,

Takata J., Karube Y., Tsuchihashi R., Kinjo J., and Mihashi

K., 2005, Antiproliferative constituents from Umbelliferae

plants VII. Active triterpenes and rosmarinic acid from

Centella asiatica, Biological & Pharmaceutical Bulletin,

28: 173–175, http://dx.doi.org/10.1248/bpb.28.173

Yun K.J., Kim J.Y., Kim J. Bin, Lee K.W., Jeong S.Y., Park H.J.,

Jung H.J., Cho Y.W., Yun K., and Lee K.T., 2008,

Inhibition of LPS-induced NO and PGE2 production by

Medicinal Plant Research 2013, Vol.3, No.3, 13

http://mpr.sophiapublisher.com

asiatic acid via NF-kappa B inactivation in RAW 264.7

macrophages: possible involvement of the IKK and

MAPK pathways, International Immunopharmacology, 8:

431–441, http://dx.doi.org/10.1016/j.intimp.2007.11.003

Zaidan M.R.S., Noor Rain, Badrul R., Adlin A., Norazah A.,

and Zakiah I., 2005, In vitro screening of five local

medicinal plants for antibacterial activity using disc

diffusion method, Tropical Biomedicine, 22: 165–170

Zhang L., Li H.Z., Gong X., Luo F.L., Wang B., Hu N., Wang

C.D., Zhang Z., and Wan J.Y., 2010, Protective effects of

Asiaticoside on acute liver injury induced by lipopoly-

saccharide/D-galactosamine in mice, Phytomedicine:

International Journal of Phytotherapy and Phytopha-

rmacology, 17: 811–819, http://dx.doi.org/10.1016/j.phy

med. 2010.01.008

Zhang X., Wu J., Dou Y., Xia B., Rong W., Rimbach G., and

Lou Y., 2012, Asiatic acid protects primary neurons

against C2-ceramide-induced apoptosis, European Journal

of Pharmacology, 679: 51–59, http://dx.doi.org/10.1016/

j.ejphar.2012.01.006

Zheng C., and Qin L., 2007, Chemical components of Centella

asiatica and their bioactivities. Journal of Chinese

Integrative Medicine, 5: 348–351, http://dx.doi.org/10.

3736/jcim20070324

Zhou J., Xie G., and Yan X., 2011, Encyclopedia of traditional

chinese medicines - molecular structures, pharmacological

activities, natural sources and applications, Berlin,

Heidelberg: Springer Berlin Heidelberg

Centella asiatica: A Comprehensive Pharmacological Review of its Therapeutic Potential

Article

Dec 2024

Centella asiatica, also referred to as gotu kola, is a well-known medicinal herb that has been used for more than 3,000 years in Chinese and ancient Indian Ayurvedic medicine. It has recently attracted interest from all around the world due to its several medicinal advantages. The pharmacological characteristics, chemical makeup, and therapeutic uses of Centella asiatica are examined in this paper. The plant, which is abundant in bioactive substances like triterpenoids and saponins, has strong anti-inflammatory, anticancer, anticonvulsant, and antioxidant properties. Among other advantages, its medicinal potential includes improving memory, reducing anxiety, and encouraging wound healing. Although its natural sources make it a desirable therapeutic alternative, the way it is administered and the patient's specific medical condition will determine its safety and efficacy. The IUCN has classified CA as endangered due to the alarming loss in its natural populations caused by uncontrolled exploitation. This underlines how urgently sustainable farming methods and more study are required to properly realize its therapeutic potential.

Carbohydrates acting as enhancers of secondary metabolites synthesis in in vitro cultures of Centella asiatica (L.) Urb.

Article

Full-text available

Apr 2025
PLANT CELL TISS ORG

Carbohydrate sources play a critical role in supporting plant growth under in vitro conditions. Centella asiatica (L.) Urb., a highly valued medicinal plant, is widely recognized for its therapeutic properties, including neuroprotective, anti-inflammatory, and anti-neurodegenerative effects. Among various carbon sources, sucrose at a 3% concentration is most commonly utilized due to its efficient uptake, metabolism, and stability. In this study, treatment with 7% xylose resulted in the highest accumulation of chlorophyll a (0.86 g/100 g fresh weight and 0.41 g/100 g fresh weight) and chlorophyll b (0.41 g/100 g fresh weight). Furthermore, bioactive compound analyses revealed that 7% xylose significantly enhanced the levels of asiaticoside (33.51 ± 0.24 mg/g DW), madecassoside (43.02 ± 0.15 mg/g DW), asiatic acid (20.03 ± 0.07 mg/g DW), and madecassic acid (22.84 ± 0.14 mg/g DW). Additionally, the total phenolic content was maximized in treatments with 7% xylose, 5% xylose, and 7% galactose. Other monosaccharides, such as 5% fructose and 5% glucose, also promoted the accumulation of bioactive compounds. Among disaccharides, 1.5% sucrose increased madecassoside levels, while 7% maltose and 5% galactose elevated both asiaticoside and madecassoside concentrations. These results emphasize the significant impact of specific carbohydrate sources on chlorophyll biosynthesis and bioactive compound production in C. asiatica, highlighting their potential to optimize in vitro culture protocols for enhanced phytochemical yields.

Centella asiatica (L.) Urb. and Hydrocotyle umbellata L. identification and quality assessment: A methodology comparison

Article

May 2024

Introduction Centella is an important genus in the Apiaceae family. It includes Centella asiatica , which has significant edible and medicinal values. However, this species is easily confused due to its similar morphological traits to Hydrocotyle umbellata , hindering its utilization in the consumer and pharmacological industries. Objective The study aims to differentiate these two closely related plant species using reliable methods of confirming the authenticity of natural herbal medicines. Methods Our work mainly focuses on the basic morphological characteristics, chemical markers, genetic fingerprints, and their biological responses. Results The plants can be clearly differentiated using their leaf shapes, stipules, petioles, inflorescences, and fruit structures. Although the phytochemical compositions of the C. asiatica extract were similar to that of H. umbellata which included flavonoids, tannins, and saponins important to the plant's ability to reduce inflammation and promote healing of wounds, the H. umbellata extract showed significantly higher toxicity than that of C. asiatica . High‐performance liquid chromatography analysis was used to identify chemical fingerprints. The result revealed that C. asiatica had major triterpene glycoside constituents including asiaticoside, asiatic acid, madecassoside, and madecassic acid, which have a wide range of medicinal values. In contrast, triterpenoid saponins were not identified in H. umbellata . Furthermore, using SCoT1–6 primers was possible to effectively and sufficiently created a dendrogram which successfully identified the closeness of the plants and confirmed the differences between the two plant species. Conclusion Therefore, differentiation can be achieved through the combination of morphometrics, molecular bioactivity, and chemical analysis.

Ethanolic Leaf Extract of Centella asiatica L. Possesses Nephroprotection in an Animal Model of Nephrotoxicity

Article

Mar 2024
INDIAN J PHARM EDUC

The Effect of Centella asiatica-Supplemented Diets on Larval Performance and Production of Macrobrachium rosenbergii (De Man, 1879)

Article

Full-text available

Dec 2024

The cultivation of Macrobrachium rosenbergii in freshwater prawn farming has globally expanded; however, it still faces challenges during the larval phase due to limited availability of high-quality seeds, which reduces production. Live Artemia nauplii are traditionally used, but they may not provide sufficient nutrition. Centella asiatica (gotu kola powder, GKP) is gaining attention for its potential growth-promoting properties. This study examined the impact of GKP-supplemented diets on larval development and growth. Larvae were initially fed Artemia until stage VI, then transitioned to a combination of Artemia and GKP-supplemented egg custard diets with varying GKP inclusion rates (0-0.8%). While no significant differences were observed in survival rate, metamorphosis rate, final production, or post-larvae (PL) per liter, the GKP-fed experimental groups performed better overall. Control diet-fed larvae were heavier than those in the 0.8% GKP-fed group, while the 0.2% GKP-fed group showed faster PL appearance. Incorporating C. asiatica powder at 0.2% yielded the best results, while the 0.8% GKP-fed group showed the lowest performance. Low GKP inclusion has the potential to support more efficient and cost-effective production methods in aquaculture. Further research should explore lower dosages over longer periods and across different age groups.

Effect of Centella asiatica ethanol extract on zebrafish larvae ( Danio rerio) insomnia model through inhibition of Orexin, ERK, Akt and p38

Article

Full-text available

Feb 2024

Background: Insomnia is difficulty initiating or maintaining sleep for at least three nights a week or more and lasting for at least 3 months. One of the molecules that play a role in the circadian rhythm of arousal system is hypocretin/orexin. Orexin activates the p38-MAPK signaling pathway and increases phosphorylated ERK1/2 levels. Centella asiatica (CA) has a role in the signal work of the MAPK/ERK, Akt, and p38 path in many various diseases. Methods: The research method used is true laboratory experimental. The research approach used was randomized control group post-test only. Zebrafish embryos aged 0-7 dpf were used in this study. The treatment group consisted of 5 groups: normal, insomnia, insomnia + 2.5 μg/mL CA, insomnia + 5 μg/mL CA, and insomnia + 10 μg/mL CA. The locomotor motion of zebrafish larvae was observed using Basler cameras on days five-, six- and seven-day post fertilization (dpf), then analyzed by using Western Blot method. Results: The results proved that exposure to CA extract was able to reduce the expression of orexin (91963 ± 9129) and p38 (117425 ± 6398) as an arousal trigger in the sleep-wake cycle, with the most optimal concentration of CA 5 μg/mL. Exposure to CA extract was also able to reduce the expression of ERK (94795 ± 30830) and Akt (60113.5 ± 27833.5) with an optimum concentration of CA 2.5 μg/mL. Conclusion: Exposure to CA extract was able to improve the sleep activity of zebrafish larvae insomnia model by extending the total inactivity time ( cumulative duration) and shortening the duration of first sleep ( latency to first) in light and dark phases through inhibition of orexin, ERK, p38, and Akt.

"MEDICINAL PLANTS FROM INDIA AS PROSPECTS OF ANTICANCER DRUG SOURCES: A COMPREHENSIVE REVIEW"

Chapter

Full-text available

Apr 2024

The incidence of cancer is steadily rising, making it one of the top causes of mortality in the world today. In many developing countries, including India, medicinal plants have been used to treat cancer and serve as an alternative to synthetic drugs known for their harmful side effects. The main objective of this review was to highlight the anticancer properties of 50 medicinal plants found in India. The review discussed the proposed anticancer pharmacological effects of these plants along with the specific bioactive compounds responsible for their anticancer effects. These plants have been found to inhibit various types of cancers such as prostate, lung,cervical,esophagus, skin,ovary, colon, blood, brain, breast,and kidney cancers. The molecular, physiological nature of cancer, stages of cancer proliferation and metastasis, different types of anticancer activity screening techniques and modern methods of cancer treatment were also discussed. Bioactive compounds identified in medicinal plants include polyphenols, flavonoids, alkaloids, saponins, triterpenes, tannins and quinones. Several major anticancer pharmacological effects have been attributed to these compounds, such as antiproliferative, cytotoxic, apoptotic, and antioxidant effects. Additionally, they have been found to induce cell cycle arrest, inhibit angiogenesis, and reduce cancer cell viability. In conclusion, the promising anticancer activity shown by the medicinal plants investigated in this study suggests that they have significant potential as a source of future readily available and affordable anticancer drugs in India. By exploring these natural alternatives, the adverse effects associated with synthetic drugs could be alleviated, offering new hope in the fight against cancer.

Anti-hyperglycemic effect of herbal formula of Moringa oleifera, Vernonia amygdalina and Centella asiatica extracts in streptozotocin-induced hyperglycemic mice

Article

Apr 2024

Role of Plant derived-medicine for controlling Cancer

Article

Full-text available

Feb 2024

This review paper has highlighted a list of plants containing active phytochemicals with anticancer potential, as well as data supporting their use in cancer therapy, animal models, and their pharmacological properties. Cancer is among the leading causes of morbidity and mortality worldwide. Cancer is a disease characterized by abnormal cell division and proliferation that result from disruption of molecular signals that control these processes. Cancer is the abnormal, uncontrolled division of cells in the body. The cancer cells when malignant, invade various parts of the body through the bloodstream. The spread of cancer from its cells or tissue of origin to another healthy part of tissues or organs is called metastasis. Some of the regular characteristics of cancers are apoptosis, angiogenesis, multiple replication, growth signal production, insensitivity to signals of anti-growth and metastasis. These features make cancer cells to have continuous growth, long time survival and the potential to invade normal cells. Moreover, if these activities are not blocked, cancer cells will continue to increase, overwhelm and finally kill the patient with cancer. Oncology is the study of cancer. An oncologist is a doctor who treats cancer and provides medical care for a person diagnosed with cancer. An oncologist may also be called a cancer specialist. Today, despite considerable efforts, cancer still remains an aggressive killer worldwide. The success rate of these therapies is diminished by toxicities, drug resistance, recurrence and treatment failure. A significant challenge associated with cancer is that treatment is as much an art as it is a science. Therefore, there is a constant demand to develop new, effective, and affordable anticancer drugs. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy, radiation therapy, immunotherapy, surgery, and stem cell therapy. Medicinal plants could also possess effective anticancer compounds that may be used as adjuvants to existing chemotherapy to improve efficacy and/or reduce drug-induced toxicity; such as chemotherapy-induced nausea and vomiting to improve patients' quality of life. Cell death is caused by the whole plant extracts via apoptosis. However, majority of plant extracts have been researched for cancer prevention rather than treatment, resulting in low efficacy and uptake in practice. Prevention is certainly an attractive cancer management strategy. Thus it might be possible to reduce the process of carcinogenesis with regular use of these plants along with a healthy lifestyle.

Role of Plant derived-medicine for controlling Cancer

Article

Full-text available

Feb 2024

Factors affecting the content of pentacyclic triterpenes in Centella asiatica raw materials

Article

Full-text available

Sep 2012
PHARM BIOL

Context: Pentacyclic triterpenes, mainly, asiatic acid, madecassic acid, asiaticoside, and madecassoside are the active constituents of Centella asitica (L.) Urban. (Apiaceae). These compounds possess various pharmacological activities that have been shown to assist with wound healing and brain enrichment. Objective: Determination of these active pentacyclic triterpenes in extracts from the various parts of C. asiatica plants harvested at different times of the year and grown in different environments. Materials and methods: The separate plant parts selected were leaves, stolons, petioles, flowers, fruits, and nodes with roots. Dried powder from each part was extracted with ethanol by microwave-assisted extraction and subjected to determination of their content of the four pentacyclic triterpenes using a HPLC method. The effects of the places of cultivation as well as harvesting periods on the content of the four pentacyclic triterpenes in the extracts were also determined. Results and discussion: Among the various parts of C. asiatica, the leaves contained the highest amount of pentacyclic triterpenes with a total content of pentacyclic triterpenes of 19.5 mg/g dry powder. However, the contents of the pentacyclic triterpenes in C. asiatica varied according to the place of cultivation and the harvesting period. C. asiatica collected from Trang, Thailand gave the highest content of total pentacyclic triterpenes (37.2 mg/g dry powder) when harvested in March, while those collected from Songkhla, Thailand gave the highest value (37.4 mg/g dry powder) when collected in December. C. asiatica collected from Nakornsrithammarat and Ratchaburi, Thailand gave the lowest content of total pentacyclic triterpenes in all experimental harvesting periods.

A Guide to Medicinal Plants: An Illustrated, Scientific and Medicinal Approach

Book

Nov 2011

Encyclopedia of Traditional Chinese Medicines - Molecular Structures, Pharmacological Activities, Natural Sources and Applications

Article

Jan 2011

Centella asiatica (Linn.) Urban: a review

Article

Jan 2007

Centella asiatica (Linn.) Urban is valued in Indian systems of medicine for improving memory and for the treatment of nervine disorders and skin diseases. It has been used extensively as memory enhancer. The present review is an up-to-date and comprehensive literature analysis of the chemistry, pharmacology and clinical trials on Centella drug.

Centella asiatica (L.): A plant with immense medicinal potential but threatened

Article

Nov 2009

Centella asiatica (L.) is a perennial, creeper, faintly aromatic and a valuable medicinal herb of both Old World and the New World. It is distributed throughout tropical and subtropical regions of World such as India, China, Nepal, Madagascar, Srilanka and Indonesia etc. The requirement of Centella asiatica is now met from natural population, leading to their gradual depletion and thus followed by its placement in the list of threatened species as mentioned by IUCN. Much of the ancient and contemporary lore surrounding this plant with its chemistry and pharmacology related to efficacy of both herbal preparations and chemical isolates are justified on the basis of experimental evidences. This paper provides its immense importance as economic plant with medicinal value as well as brief information of its products in the market launched, showing its dependability.

Medicine at your Feet: Healing Plants of the Hawaiian Kingdom Centella asiatica (Pohe kula)

Article

Microbial transformation of asiatic acid

Article

Dec 2012
J ASIAN NAT PROD RES

Asiatic acid (1), a major pentacyclic triterpene of Centella asiatica, was subjected to transformation by Penicillium lilacinum ACCC 31890, Fusarium equiseti CGMCC 3.3658, and Streptomyces griseus CGMCC 4.18 strains. Incubation of asiatic acid with P. lilacinum ACCC 31890 and F. equiseti CGMCC 3.3658 gave an identical product: 2α,3β,15α,23-tetrahydroxyurs-12-en-28-oic acid (2). Biotransformation of asiatic acid by S. griseus CGMCC 4.18 resulted in three derivatives: 2α,3β,21β,23-tetrahydroxyurs-12-en-28-oic acid (3), 2α,3β,23-trihydroxyurs-12-en-28, 30-dioic acid (4), and 2α,3β,23,30-tetrahydroxyurs-12-en-28-oic acid (5). The structures of those derivatives were deduced from their spectral data. Products (2), (3), and (4) were new compounds. In addition, the in vitro cytotoxicities of those derivatives along with 1 were evaluated with several human cancer cell lines.

Production of Polyclonal Antibody Against Madecassoside and Development of Immunoassay Methods for Analysis of Triterpene Glycosides in Centella asiatica

Article

May 2013
PHYTOCHEM ANALYSIS

Centella asiatica (L.) Urban consists of two major triterpene glycosides, asiaticoside (AS) and madecassoside (MA), as active components used for wound healing and enhancing memory. To produce a polyclonal antibody against madecassoside (MA-PAb) and develop enzyme-linked immunosorbent assay (ELISA) and Eastern blotting methods for quantitative analysis of triterpene glycosides in Centella asiatica. An ELISA method was developed using polyclonal antibody against MA. An Eastern blotting method on the PES membrane was established for determination of MA and AS. The immunoassays were validated for sensitivity, precision, specificity and accuracy. The prepared MA-PAb shows specificity to MA and AS. The measuring range of triterpene glycosides was 0.39–50 µg/mL using the ELISA method. An Eastern blotting method was developed for determining individual MA and AS, which could be detected in the range of 62.5–500 ng. The limit of detection for MA and AS was 31.25 ng. The two methods developed showed good specificity, precision, and accuracy, and also correlated with high-performance liquid chromatography. These immunoassays have several advantages that include high sensitivity as well as being rapid and facile for determination of the triterpene glycosides in C. asiatica. Copyright

Antipyretic and Anti-inflammatory Effects of Asiaticoside in Lipopolysaccharide-treated Rat through Up-regulation of Heme Oxygenase-1

Article

Aug 2013
PHYTOTHER RES

Asiaticoside (AS), a triterpenoid isolated from Centella asiatica, has been found to exhibit antioxidant and anti-inflammatory activities in several experimental animal models. However, the underlying mechanisms remain elusive. In this study, we provide experimental evidences that AS dose-dependently inhibited lipopolysaccharide (LPS)-induced fever and inflammatory response, including serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, liver myeloperoxidase (MPO) activity, brain cyclooxygenase-2 (COX-2) protein expression and prostaglandin E(2) (PGE(2) ) production. Interestingly, AS increased serum IL-10 level, liver heme oxygenase-1 (HO-1) protein expression and activity. Furthermore, we found that the suppressive effects of AS on LPS-induced fever and inflammation were reversed by pretreatment with ZnPPIX, a HO-1 activity inhibitor. In summary, our results suggest that AS has the antipyretic and anti-inflammatory effects in LPS-treated rat. These effects could be associated with the inhibition of pro-inflammatory mediators, including TNF-α and IL-6 levels, COX-2 expression and PGE(2) production, as well as MPO activity, which might be mediated by the up-regulation of HO-1. Copyright © 2012 John Wiley & Sons, Ltd.

Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model

Article

Aug 2012

Wound healing proceeds through a complex collaborative process involving many types of cells. Keratinocytes and fibroblasts of epidermal and dermal layers of the skin play prominent roles in this process. Asiaticoside, an active component of Centella asiatica, is known for beneficial effects on keloid and hypertrophic scar. However, the effects of this compound on normal human skin cells are not well known. Using in vitro systems, we observed the effects of asiaticoside on normal human skin cell behaviors related to healing. In a wound closure seeding model, asiaticoside increased migration rates of skin cells. By observing the numbers of cells attached and the area occupied by the cells, we concluded that asiaticoside also enhanced the initial skin cell adhesion. In cell proliferation assays, asiaticoside induced an increase in the number of normal human dermal fibroblasts. In conclusion, asiaticoside promotes skin cell behaviors involved in wound healing; and as a bioactive component of an artificial skin, may have therapeutic value.

Current updates on Centella asiatica: Phytochemistry, pharmacology and traditional uses

Abstract

Recommended publications

Genus Tetrastigma: A review of its folk uses, phytochemistry and pharmacology

A Review of the Phytochemistry and Pharmacology of the Medicinal Plant: Khaya Senegalensis (Desr.) A...

Current Updates on Centella asiatica : Phytochemistry, Pharmacology and Traditional Uses

Ethnopharmacological Importance of Centella asiatica with Special Reference to Neuroprotective activ...

Ethnopharmacological importance of Centella asiatica with special reference to neuroprotective activ...

Centella asiatica: from folk remedy to the medicinal biotechnology - a state revision