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Abstract Plants have been demonstrated extraordinary source of medicine, and recently focus on medicinal plant research has
increased. Centella asiatica is well known for its traditional uses and medicinal properties for the treatment of many diseases. The
published literatures mention the use of this plant as whole and bioactive compounds isolated are widely used in the treatment of
various human ailments. C. asiatica reported to possess various pharmacological activities: antimicrobial activity, anticancer activity,
wound healing activity, neuroprotechtive activity, immunomodulatory activity, anti-inflammatory activity, hepatoprotective activity,
insecticidal activity, and antioxidant activity. C. asiatica is also rich in flavonoids and terpenoids compounds among them asiatic acid,
asiaticoside, madecassoside is well characterized for its pharmacological value. The present review summarized widespread
information on phytochemistry, isolated and characterized bioactive compounds, pharmacological properties, in vitro propagation and
traditional uses of the important medicinal plant C. asiatica.
Keywords Centella asiatica; Medicinal Plants; Triterpenes; Terpenoids phytochemistry; Pharmacology; Neuroprotechtive activity;
Wound healing actitivty; Anti-inflammatory activity; Anticancer activity
Background
Medicinal plants are an important episode in the internodes (Jamil et al., 2007; Koh et al., 2009).
medical sector. Around 5 000 species have specific Glabrous leaves, 1-3 arising from each node of the
therapeutic value among 250 000 higher plant species stems, are green, fan-shaped or round renifrom,
on earth (Joy et al., 1998). Centella asiatica has a long 1.4 cm by 1.7 cm with crenate or dentate margin
history in ancient Ayurvedic remedy, used in wound (Jamil et al., 2007; Koh et al., 2009). Flowers
healing, cleansing for skin problem and digestive occurring in July- September are umbels with 3-4
disorders (Chevallier, 2001) and effective in treatment white or light purple-to-pink petals bearing 4mm long
of stomach ulcers, mental fatigue, diarrhea, epilepsy, oval to globular shaped fruit (Chauhan, 1999; Jamil et
hepatitis, syphilis and asthma (Goldstein and al., 2007; Koh et al., 2009). The most used part for
Goldstein, 2012). Such traditional uses and reputation medicinal purposes is dried whole plant, leaves and
of this species cross over the boundary limit of stems. C. asiatica plant is indigenous to Bangladesh,
Bangladesh, India, and Srilanka and now extensively India, West Pakistan, China, Japan, America and the
used in the West (Chevallier, 2001; Meulenbeld and pacific (Koh et al., 2009). This plant is commonly
Wujastyk, 2001). C. asiatica and Hydrocotyle asiatica, seen in moist, sandy or clayey soils waste places
belongs to family Apiaceae (Umbelliferae) are used (Jamil et al., 2007).
synonymously and commonly known as Thankuni
(Bengali), Bemgsag/Brahma-Manduki/Gotukola/Khu- Phytochemistry
lakhudi/Mandookaparni (Hindi), Indian Pennywort/ C. asiatica is a rich source of amino acids, flavonoids,
Marsh Pennywort/ Gotu kola (English) (Singh et al., terpenoids, essential oils, alkaloids etc. (Table 1).
2010). C. asiatica is creeping, perennial herb with up Most of the phytochemical studies concentrated on
to 2m long slender and tender horizontal reddish leaves and the constituents vary depending upon the
prostrate stolons, characterized by long rooting geographical distribution (Chong and Aziz, 2011).
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Table 2 Structure and biological activities of bioactive compounds isolated from C. asiatica
Name of the compounds Structure Biological activity References
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Continuing table 2
Name of the compounds Structure Biological activity References
Linolenic acid Nutrient, inhibits cancer cell invasion, 5α-reductase (Jamil et al.,
(C 18 H 30 O 2 ; inhibitor 2007; Zhou et
mw=278.44) al., 2011)
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Continuing table 2
Name of the compounds Structure Biological activity References
Oleic acid (C 18 H 34 O 2 ; Increases absorption through skin, dermatitis, inhibits (Jamil et al.,
mw=282.47) cancer cell invasion 2007; Zhou et
al., 2011)
skin inflammation (eczema, atopic dermatitis, leprosy, asiatica exerts diverse pharmacological activities such
varicose ulcers, etc.) fever, intestinal problems and as antibacterial, antidepresent, antiemetic, antineo-
genitourinary conditions (Belcaro et al., 2011). C. plastic, antioxidant, antithrombotic, anxiolytic,
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Goel, 2001). Administration of 100 mg/kg of body pure substance) were prepared and evaluated for
weight of aqueous extract of C. asiatica, just 1 hour wound dressings and loaded herbal substances were
before irradiation with 8Gy 60Co- γ rays was found found stable up to 4 months, promotes proliferation
most radioprotective in Swiss Albino Mouse (Sharma and upregulating the production of collagen of the
and Sharma, 2002) and further study revealed that seeded (Suwantong et al., 2010). The clinical efficacy
100mg/kg of body weight of dried powdered extract and side effects of the oral C. asiatica extract capsule
of C. asiatica had found to be effective against in the diabetic wound healing was investigated
modified 60Co-γ irradiation induced damage in the (Paocharoen, 2010). Madecassoside showed enhance
mouse liver (Sharma and Sharma, 2005). 70% wound-healing and diminish keloid formation in
ethanolic extract of C. asiatica significantly reduced primary keloid-derived fibroblasts, originating from
radiation-induced damage to DNA (Joy and Nair, human earlobe keloids (Song et al., 2012).
2009). microRNA (miRNA) expression profiling
Memory enhancing Activity: Since the ancient time,
analysis was used to evaluate the protective effects of
C. asiatica is used to enhance intelligence and
C. asiatica against Ultraviolet B damage in human
improve cognitive function. Oral administration with
keratinocytes, disclosed that miRNAs with altered
200 mg/kg of body weight aqueous extract during
expression were functionally related with cell
postnatal development stage increased brain function
proliferation and inhibition of apoptosis, may prevent
in juvenile and young adult mice (Rao et al., 2005).
the skin damage (An et al., 2012).
Enhanced working memory and improved self-rated
Wound healing activity: A large number of reports mood were observed in 28 patients after higher dose
have been found about the wound healing activity of administration of C. asiatiac extract preparations
C. asiatica (Temrangsee et al., 2011). Aqueous extract (Wattanathorn et al., 2008). Asiatic acids isolated from
of C. asiatica was used to formulate ointment, cream C. asiatica showed enhancing learning and memory
and gel, which evaluate for wound healing in rats properties in male Spraque–Dawley rats (Nasir et al.,
showed faster epithelialisation and higher rate of 2011b).
wound contraction (Sunilkumar et al., 1998).
Burns: C. asiatica extract and its active constituents
Dexamethasone suppressed wound in Wistar Albino
are very effective against burns caused by boiling
rats could be healed by ethanolic leaf extracts as like
water, electric current or gas exploitation.
as normal model (Shetty et al., 2006). In a recent
Combination of C. asiatica extract with an antibiotic
study in 200 diabetic patients revealed positive result
was anti-infectious beside healing burns (Salas et al.,
with C. asiatica extracted capsule without any adverse
2005). Low dose 10−8% to 10−12% (w/w) of
effect in the department of Surgery, Thammasat
asiaticoside application facilitated repairing in mice
University Hospital (Paocharoen, 2010). Wound
burned wound (Kimura et al., 2008).
healing activity of asiaticoside was also reported in
guinea pig model at dose 1 mg/kg of body weight and Anti-psoriatic Activity: C. asiatica shows anti-
in the chick chorioallantoic membrane model at psoriatic effect on SVK-14 keratinocyte due to the
concentration 40 µg/disk (Shukla et al., 1999). The presence of triterpenoid glycosides (Sampson et al.,
effects of asiaticoside in human periodontal ligament 2001).
cells (HPDLs) proliferation, protein synthesis, and
osteogenic differentiation were investigated and Antimicrobial Activity: C. asiatica shows
showed enhanced periodontal tissue healing antibacterial activity on both Gram positive and Gram
(Nowwarote et al., 2012). At low concentrations negative bacteria. Growth inhibition of Gram positive
aqueous extract of C. asiatica promote epithelium Bacillus subtilis and Gram negative Pseudomonas
wound healing in rabbit corneal epithelial (RCE) cells aeruginosa, P. cichorii and Escherichia coli was
(Ruszymah et al., 2012). Ultra-fine cellulose acetate observed in the disc diffusion test of hexane and ethyl
fiber mats containing asiaticoside (in crude extract or acetate extracts of C. asiatica (Escop and
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Phytotherapy, 2003). 1 000 µg/disc of hot methanolic which could be significantly improved in six weeks by
extract is moderately effective on Staphylococcus administration of C. asiatica (150 and 300 mg/kg of
aureus and Methicillin Resistant S. aureus (Wild Type) body weight) (Kumar et al., 2011). Chronic aluminum
(Zaidan et al., 2005). Micobacterium tuberculosis and exposure in rat induce cognitive dysfunction, apoptosis,
M. leprae were reported to be more sensitive to oxidative stress and mitochondrial enzyme alteration
liposomal asiatocoside than free asiatocoside (Fugh- and administration of C. asiatica found significantly
Berman, 2003). Higher antiviral activity was also decreased aluminum concentration, improved memory
reported with aqueous extract of C. asiatica against performance, oxidative defense, acetylcholinestrease
type 2 Herpes simplex virus (Escop and Phytotherapy, activity, caspase-3 and reversal of mitochondrial
2003). enzyme activity as compared to control (Prakash and
Kumar, 2012). The psychoactive and antioxidant role
Lervicidal Activity: Haemaphysalis bispinosa (the
of ethanolic extract of C. asiatica in middle cerebral
adult cattle tick), Paramphistomum cervi (sheep fluke),
artery occlusion (MCAO) in rats was evaluated and
Anopheles subpictus and Culex tritaeniorhynchus
revealed that administration of C. asiatica extract
showed sensitivity to hexane, chloroform, ethyl
restored histological morphology of brain, diminished
acetate, acetone, methanol extract of C. asiatica but
infarction volume, greatly improved the
methanol extract was the most effective on P. cervi
neurobehavioral activity (Tabassum et al., 2012).
and A. subpictus (Bagavan et al., 2009). 3-O-[a-L-
arabinopyranosyl] 2 a, 3 ß, 6 ß, 23-a tetrahydroxyurs- Asiatic acid possess neuroprotective effects in vitro
12-ene-28-oic acid, a triterpenoid glycoside, exhibited and in vivo (Xu et al., 2012b), nootropic activity with
inhibitory activity against larvae of Spilarctia oblique therapeutic implications for patients with memory loss
(Shukla et al., 2000). (Shinomol et al., 2011). Increased dendritic length and
branches was observed in rat after fresh leaves extract
Anti-hyperglycemic effect: Oral administration of
administration (Mohandas Rao et al., 2006). Three
asiatic acid and glibenclamide to streptozotocin
derivatives of asiatic acid were significantly effective
induced diabetic rats for 45 days prevented the altered
in protecting excess glutamate exposed neurons on
activities of key enzymes (glucose-6-phosphatase and
cultured cortical cells (Lee et al., 2000; Xu et al.,
fructose-1,6-bisphosphatase) related with hypergly-
2012b). Non-polar fraction of ethanolic extract
cemia (Ramachandran and Saravanan, 2012).
containing asiatic acid which found to be increased in
Neuroprotective Activity: Aqueous extract showed neurite outgrowth in human SH-SY5Y cells in the
neuroprotective effect by increasing the antioxidant presence of nerve growth factor and administration of
enzyme level in mice corpus striatum and ethanolic extract through drinking water demonstrated
hippocampus (Haleagrahara and Ponnusamy, 2010). axonal regeneration in Male Sprague-Dawley rats
Fresh leaf extract of C. asiatica was investigated on (Soumyanath et al., 2005). Asiatic acid was reported
dendritic morphology of amygdaloid neurons on adult for the treatment of cerebral ischemia in mice
rats, one of the regions concerned with learning and (Krishnamurthy et al., 2009). Asiatic acid showed
memory, showed a significant increase in the dendritic potential neuroprotective activity against
length and branching points (Rao et al., 2012). Water C2-ceramides-induced cell death in primary cultured
extract of C. asiatica inhibit the activity of subtypes of rat cortical neuronal cells (Zhang et al., 2012) and
phospholipase A2 (PLA2), which is related with asiaticoside significantly attenuated 1-methyl-4-
neurodegenerative disease (Defillipo et al., 2012). phenyl-1,2,3,6-tetrahydropyridine (MPTP) induce
n-hexane, chloroform, ethyl acetate, n-butanol extract Parkinsonism in rat model (Xu et al., 2012a).
of C. asiatica showed anticonvulsant and neuropro- Asiaticoside was recommended for epilepsy, stroke,
tective activity in male albino rats (Visweswari et al., multiple sclerosis and other neuropsychiatric disorders
2010). D-galactose induced oxidative and mitochon- (Barbosa et al., 2008).
drial dysfunction and cognitive impairment in mice,
Venous insufficiency Activity: Patients suffering
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