Articles

Centella asiatica

Synonyms

Hydrocotyle asiatica L.

Vernacular Names:

Malaysia Pegaga
English Pennywort, Indian pennywort, centella, gotu kola
India Mandukaparni

General Information

Description

An evergreen perennial creeping herb commonly found in moist places [1]. Used in salads and cooked as a vegetable. A trailing herb with rounded simple leaves, slender stems and inconspicuous flowers formed in short clusters.

Plant Part Used

Leaves

Chemical Constituents:

Active principles are pentacyclic tirterpenes, namely, asiatic acid, asiaticoside, madecassic acid and madecassoside [2]. Triterpenes with healing potential were isolated, namely, terminolic acid, asiaticoside-B while sceffoleoside A and saponins (centellasaponins B,C and D) with four ursane- and oleanane-type triterpene oligoglycosides were isolated from Centella asiatica grown in Sri Langka [1]. Other minor saponins are centelloside, brahmoside and brahminoside [3]. The essential oil from C. asiatica grown in South Africa contains 11 monoterpenoid hydrocarbons (20.2%), 9 oxygenated monoterpenoids (5.46%), 14 sesquiterpenoid hydrocarbons (68.8%), 5 oxygenated sesquiterpenoid (3.9%) and 1 sulphide sesquiterpenoid (0.76%). The predominant constitutes were b-caryophyllene (19.08%), bicyclogermacrene (11.22%), germacrene B (6.29%) and myrcene (6.55%) [1]. Other reports included trans-b-farnesene and germacrene D as prominent constituents of the essential oil [1].

Traditional Use:

C. asiatica has been used as a wound-healing agent and a constituent of a brain tonic for the mentally challenged [2]. It has also been used traditionally and in Ayurvedic medicine for central nervous system ailments including failing memory, insomnia, depression, stress and epilepsy [4]. In South Africa it was used to treat leprosy, wounds, cancer, fever and syphillis, while in Europe, the extract has been used for many years to treat wounds [1]. The plant is also used to treat acne and allergies [1] and as a psycho-physical regenerator and blood purifier [3].  In China, Centella asiatica has been used for a long time to treat dermal wounds and leprosy patients [5]. Other folk medicine uses are for abscesses, headache, asthma, bronchitis, catarrh, convulsions, dysentery, eczema, gonorrhea, hypertension, jaundice, pleuritis, rheumatism, spasms, tuberculosis, ulcers, urethritis and as a diuretic [6]. In Kenya, the leaves were applied to the skull amongst the Kisii tribe to improve healing [6].

Pre-Clinical Data

Pharmacology

Wound-healing activity

A formulation which contained Centella asiatica plant extract induces proliferation of granulation tissue and increased tensile strength when applied locally on wounds in rats and decreased the area of skin necrosis caused by burns [7]. The plant purportedly reduced scarring and stimulated skin growth by acting on the production of collagen fibres by fibroblasts and resulted in a decrease in the inflammatory reaction and myofibroblast production [8]. Asiaticoside, a major constituent of the herb, promoted wound-healing by reducing lipid peroxide levels in wounds while it increased enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (vitamin E and ascorbic acid) antioxidant levels [9].     

Antibacterial activity

The essential oil of Centella showed a broad spectrum of antibacterial activities against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Shigella sonnei) organisms [1]. Activity against Gram-positive bacteria was greater than against Gram-negatives. Germacrene compounds in the essential oil are known to be strong antimicrobial and antitumour agents [1].  

Antitumour activity

Methanolic extract of Centella asiatica (100µg/mL) showed 100% cytotoxicity to two tumour cell lines (Dalton’s ascites tumour cells and Ehrlich ascites tumour cells) after a 3 hour incubation at 37oC [10]. The acetone fraction of Centella asiatica extract, a partially purified fraction (3.5 & 8µg/mL), inhibited the proliferation of mouse lung fibroblast cells after exposure for 6-7 days at 37oC. Both the crude extract and the acetone fraction of Centella asiatica significantly reduced the development of murine solid tumours when administered simultaneously with tumour transplantations or given 10 days prior to tumour transplantation. The latter finding suggested a mechanism which involves stimulation of the immune system. The crude extract also significantly reduced ascites tumour growth and increased the life span of tumour bearing mice. The mechanism may involve inhibition of DNA synthesis [10].  

Neuropharmacology and antioxidant activity

The hydroalcoholic extract of C. asiatica leaves possesses potential anticonvulsant, antioxidant and central nervous system (CNS) depressant actions [4]. The extract (100mg/kg) showed 50% protection while a higher dose (200mg/kg) completely protected against pentylenetetrazol-induced convulsions in rats. The extract also protected against convulsions induced by an increase in current electroshock and by strychnine. Spontaneous motor activity was reduced while diazepam withdrawal-induced autonomic hyperactivity was potentiated as was the pentobarbitone sleeping time in mice [4]. The extract (100-150mg/kg) significantly reduced the normal body temperature of mice, while in brain homogenates it (1.3-40mg/mL) reduced the formation of lipid peroxidation products [4].

Aqueous extract of C. asiatica (100-300mg/kg) was able to prevent cognitive deficits in intracerebroventricular streptozotocin-induced cognitive impairment in rats after 14 and 21 days indicating improved acquisition and retention of memory [11]. These doses of C. asiatica did not affect spontaneous locomotor activity in these rats thus excluding the possibility that the CNS depressant/stimulant activity of the herb had contributed to the changes in the passive avoidance and elevated plus maze tests. After 21 days of treatment in the same groups of rats, the extract (200 & 300mg/kg) significantly reduced brain malondialdehyde levels and increased brain glutathione levels without affecting brain superoxide dismutase activity while brain catalase levels were increased by the highest dose of the extract (300mg/kg) [9].

C. asiatica extract (0.3%) and powder (5%) reduced oxidative stress when given to H2O2-exposed rats for 25 weeks [12]. There was a reduction in erythrocyte malondialdehyde levels as well as a decrease in the superoxide dismutase activity of these rats given C. asiatica although the catalase activities were higher than in the H2O2-fed rats.  

The aqueous extract of C. asiatica was shown to be able to improve oxidative stress by being a neuroprotective as well as regulate endogenously [22]. C. asiatica compounds decreases lipid peroxidation through antioxidant activities that is reducing radical oxygen species [25].

Other effects

Asiatic acid and its derivatives protected cultured neurons from glutamate-induced excitotoxicity [9].

Oral administration of C. asiatica water extract and asiaticoside reduced the size of acetic acid-induced gastric ulcers in rats at 3 and 7 days in a dose-dependent manner with concomitant attenuation of myeloperoxidase activity in the ulcer tissues [13]. Cell proliferation and angiogenesis were promoted, the expression of basic fibroblast growth factor in ulcer tissues in rats treated with extract or compound were upregulated [13]. The aqueous extract of C. asiatica (0.05g, 0.25 and 0.50g/kg) significantly inhibited ethanol-induced gastric lesions and decreased mucosal myeloperoxidase in a dose dependent manner when the extract was given before ethanol administration [14]. These results suggest that C. asiatica protected the gastric mucosa by improving the integrity of the mucosal lining while reduction of myeloperoxidase and gastric lesions could be due to a decrease in the recruitment of neutrophils by C. asiatica or to its free radical scavenging activity [14].

The asiaticoside constituent of C. asiatica is shown to inhibit the phospholipase A enzymes in the brain [23]. The extract of C.asiatica also regulates the genotoxicity which will lead to the protection of human lymphocytes [24]. In addition, the plant extract plays a role in memory enhancing as well as improvement of mood in high dose administration manner [26].

Anxiolytic activity

The triterpine contents in C.asiatica extract showed anxiolytic activity and there are possibility of synergistic effect between terpene and asiaticoside [27].

Toxicities

Aqueous extract of C.asiatica (5mg/plate)lack cytotoxicity and mutagenicity on Salmonella typhimurium TA98 or TA100 with or without S9 mixture [5]. Acetone fraction of C.asiatica extract did not induce cytotoxicity in normal human lymphocytes at a 50µg/mL [10]. Oral administration the crude extract and the acetone fraction of C. asiatica to normal and tumour bearing mice at maximal concentrations of 500 mg/mouse did not produce any toxic symptoms while the body weights of the mice were increased [10].

Asiaticoside, a major triterpenic acid in Centella asiatica was thought to be allergenic. [14] Although in guinea pigs, centella raw extract and its triterpenic constitutents asiaticoside, asiatic acid and madecassic acid were considered to be weak sensitizers [6].

Clinical Data

Clinical Trials

A herbal medicament containing C. asiatica and Punica granatum extracts in the form of biodegradable chips for subgingival application elicited significant improvements of pocket depth and attachment level in adult periodontitis patients [15].

Slimming liposomes containing esculoside, C. asiatica extracts, caffeine and L-carnitine potentially could provide a slimming effect in human volunteers [16]. The slimming liposomes induced a dramatic increase in cyclic adenosine monophosphate content in human adipocytes, with a subsequent rise in the nonesterified fatty acids content of the incubation medium in in vitro experiments. The slimming liposomes antagonized a2-adrenergic receptors which should subsequently lead to down-regulation of lipolysis [16].

Thirty patients with diabetic microangiopathy treated for six months with a total triterpenic fraction of C. asiatica (60mg twice daily) led to significant improvement in microcirculation, decreased capillary permeability and also protected against microcirculation deterioration in these patients [17].

In a double-blind placebo-controlled study, a single 12g dose of C. asiatica (encapsulated crude powder herb) was administered to 20 healthy subjects and 20 controls given the placebo [18]. Compared with the placebo-treated group, C. asiatica significantly attenuated the peak acoustic startle response amplitude at 30 and 60 minutes after treatment without having any significant effect on self-rated mood, heart rate or blood pressure. This early findings suggest that the herb may have anxiolytic activity in humans.

Adverse Effects in Human:

Hepatotoxicity [3] was seen with C. asiatica ingestion while contact dermatitis [19][20][21] was presented after topical administration of the herb or its constituent.

Use in Certain Conditions:

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

Three women aged 61, 52 and 49 years old developed jaundiced after taking C. asiatica for 30, 20 and 60 days, respectively [3]. Their respective pathological diagnoses were granulomatous hepatitis with marked necrosis and apoptosis, chronic hepatitis with cirrhotic transformation and intense necroinflammatory activity, and granulomatous hepatitis. All patients improved with discontinuation of C. asiatica although damage recurred in the first patient who again took the herb for two weeks. The second woman reported a similar history a year before accompanied by elevated hepatic enzymes and a negative viral serology when she took the herb for six months. At that time, the jaundice disappeared one month after stopping the herb. The damage produced by C. asiatica was attributed to the triterpene active principles present in the herb which may have induced apoptosis and cell death through an alteration of cell membranes. An immune-mediated mechanism was postulated to underlie the damage as autoantibodies and granulomas were present [3].

A 38-year old man developed eczematous response on his ears to a preparation which contained C. asiatica extract [21]. He showed positive patch tests with GEIDC standard series and C. asiatica extract. An 18-year old woman presented with a pruritic eczematous eruption on an interdigital joint and face following the topical application of an ointment that contained C. asiatica extract [14]. She showed positive patch tests to the C. asiatica ointment preparation (applied as is) and to a titrated extract of C. asiatica. A 42-year old woman with no atopic history developed severe dermatitis of the legs after application of a cream that contained C. asiatica extract [20]. Patch testing with C. asiatica extract showed positive in this woman. Four women aged 33, 23, 26 and 18 years old developed contact dermatitis following the application of an ointment which contained C. asiatica extract for between 4 to several weeks [19]. All four women showed positive patch tests with the ointment.

Read More
 
1) Cultivation
2) Botanical Info
3) Medicinal Herbs

References

  1. Oyedeji OA and Afolayan AJ. Chemical Composition and Antibacterial Activity of the Essential Oil of Centella asiatica Growing in South Africa. Pharmaceutical Biology. 2005; 43 (3) : 249–252, 2005
  2. Inamdar PK, Yeole RD, Ghogare AB and de Souza NJ. Determination of biologically active constituents in Centella asiatica. Journal of Chromatography A. 1996; 742: 127-130
  3. Jorge OA and Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Revista Espanola De Enfermedades Digestivas. 2005; 97(2): 115-124
  4. Ganachari MS, Babu SVV and Katare SS. Neuropharmacology of an extract derived from Centella asiatica. Pharmaceutical Biology. 2004; 42(3): 246-252
  5. Yen GC, Chen HY and Peng HH. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants. Food and Chemical Toxicology . 2001; 39: 1045-1053
  6. View Abstract: Hausen BM. Centella asiatica (Indian Pennywort), an Effective Therapeutic But a Weak Sensitizer. Contact Dermatitis. 1993;29(4):175-79.
  7. Vogel HG, De Souza NJ and D'sa A. Effects of terpenoids isolated from Centella asiatica of granuloma tissue. Acta Therapeutica . 1990; 16: 285-298
  8. Ortiz KJ and Yiannias JA. Contact dermatitis to cosmetics, fragrances and botanicals . Dermatologi Therapy. 2004; 17: 264-271
  9. Kumar MHV and Gupta YK. Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer's disease in rats . Clinical and Experimental Pharmacology and Physiology. 2003; 30: 336-342
  10. Babu TD, Kuttan G and Padikkala J. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L) Urban . Journal of Ethnopharmacology . 1995; 48: 53-57
  11. View Abstract: Russell IJ, et al. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol. May1995;22(5):953-8.
  12. Wolfe F. Fibromyalgia: on diagnosis and certainty. J Musculoskel Pain. 1993;1(3,4):17.
  13. Cheng CL, Guo JS, Luk J and Koo MW. The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats. Life Sci. 2004; 74(18): 2237-49
  14. View Abstract: Cheng CL, Koo MW. Effects of Centella asiatica on Ethanol Induced Gastric Mucosal Lesions in Rats.Life Sci. Oct2000;67(21):2647-53.
  15. Sastravaha G, Yotnuengnit P, Booncong P, Sangtherapitikul P. Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts. A preliminary study . J Int Acad Periodontol. 2003; 5(4): 106-15
  16. Tholon L, Neliat G, Chesne C, Saboureau D, Perrier E, Branka JE. An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of slimming liposomes: An unexpected alpha(2)-adrenergic antagonism . J Cosmet Sci. 2002; 53(4): 209-18
  17. Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Bavera P, Bucci M, Ippolito E. Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology. 2001; 52(2): S49-54
  18. Bradwejn J, Zhou Y, Koszycki D, Shlik, J. . 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, . 2000; 20(6): 680-684
  19. Eun HC and Lee AY. Contact dermatitis due to madecassol. Contact Dematitis. 1985; 13(5): 310-313
  20. Izu R, Aguirre A, Gil N and Diaz-Perez JL. Allergic contact dermatitis from a cream containing Centella asiatica extract . Contact Dermatitis. 1992; 26: 192-193
  21. Bilbao I, Agiurre A, Zabala R, Gonzalez R, Raton J and Diaz Perez JL. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract. Contact Dermatitis. 1995; 33: 435-436
  22. George K. Shinomol, Muralidhara. Effect of Centella asiatica leaf powder on oxidative markers in brain regions of prepubertal mice in vivo and its in vitro efficacy to ameliorate 3-NPA-induced oxidative stress in mitochondria. Phytomedicine. November 2008;11(15):971-984  
  23. N.R. Barbosa, F. Pittella, W.F. Gattaz. Centella asiatica water extract inhibits iPLA2 and cPLA2 activities in rat cerebellum. Phytomedicine. 17 october 2008;10(15):896-900  
  24. Siddique Y. H., Ara G., Beg T., Faisal M., Ahmad M., Afzal M.. Antigenotoxic role of Centella asiatica L. extract against cyproterone acetate induced genotoxic damage in cultured human lymphocytes. Toxicology in Vitro. February 2008;1(22):10-17
  25. Hussin M., Abdul-Hamid A., Mohamad S., Saari N., Ismail M., Bejo M. H.. Protective effect of Centella asiatica extract and powder on oxidative stress in rats. Food Chemistry. 2007;2(100):535-541
  26. Wattanathorn J., Mator L., Muchimapura S., Tongun T., Pasuriwong O., Piyawatkul N., Yimtae K., Sripanidkulchai B., Singkhoraard J.. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. Journal of Ethnopharmacology. 5 March 2008;2(116):325-332
  27. P. Wijeweera, J.T. Arnason, D. Koszycki, Z. Merali. Evaluation of anxiolytic properties of Gotukola – (Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine. 24 November 2006;9-10(13):668-676