Family

Apiaceae.

Parts Used

Aerial parts (or entire plant).

Common Forms

Dried leaves, by infusion.

• Tincture, Fluid extract:   45% alcohol.

• Standardized Extracts:   Triterpene fraction gotu kola (TFGC); titrated extract Centella asiatica (TECA); total triterpene fraction of Centella asiatica (TTFCA) based on total triterpenes (typically 40% asiaticosides, 30% madecassic acid, 30% asiatic acid). Manufacturers’ preparations may vary.

Strategic Considerations

In Ayurvedic medicine, centella (gotu kola) is regarded as a Rasayana herb ( rasa , “essence,” and ayana , “enters”). Rasayana tonic herbs are believed to rejuvenate and revitalize mind-body-spirit. ¹ Centella has been used in traditional South Asian medicine as a topical remedy for leprosy, eczema, psoriasis, and ulcerous skin conditions, as well as a depurative and tonic. Western uses of gotu kola reflect the traditional indications, with primary emphasis on topical effects, including prevention of keloids and hypertrophic scars, treatments of burns, general acceleration of cicatrization and wound healing after surgery or trauma, and treatment for venous insufficiency, leg ulcers, and varicose and postthrombotic issues. The Rasayana aspects of the herb, in Western terms adaptogenic, such as its effects on stress and cognitive performance, resulted in increased popularity and widespread adoption of the remedy by Western herbal practitioners, despite only moderate support in the clinical literature for adaptogenic effects.

Despite its recent popularity, gotu kola is underrepresented in modern therapeutic literature. In the 1983 British Herbal Pharmacopoeia, gotu kola was mentioned only for its topical dermatological and vulnerary actions. ² A more recent monograph by the World Health Organization (WHO) ³ restricts supported therapeutic indications to topical use for wounds, burns, and ulcerous skin ailments, as well as internal use for venous disorders and treatment of stress-induced ulcers.

Much of the literature on gotu kola draws on data from earlier studies (1950s through 1970s), primarily from the Indian and other Asian (Thai, Vietnamese, Indonesian) sources, supported by secondary reviews from African ethnobotany and ethnopharmacological sources. The pharmacological and clinical findings extrapolated from this earlier and limited research have not generally been replicated and can be considered problematic. As a result, depending on the variable emphasis placed on these sources by different reviewers, differing portrayals of the herb have appeared in the secondary literature.

The monograph by WHO ³ tends to underemphasize the earlier data and paints a narrow, but evidentially accurate, picture of gotu kola primarily as a dermatological agent. Other, secondary sources accept the earlier data without qualification. ⁴ Predictably, however, more derivative sources have the extrapolated further from this secondary literature to suggest interactions that are entirely speculative and unrelated to present clinical uses of the herb. ⁵ In the authoritative botanical literature, however, gotu kola has no known listed interactions with pharmaceuticals. ³ Clinical reports of any interactions with either galenical extracts or triterpene-enriched preparations are unavailable. From an integrative perspective and drawing on more recent research, interactions between gotu kola and pharmaceuticals (and other natural agents) must be considered in the clinical areas of (1) wound healing in relation to trauma and surgery; (2) venous insufficiency and related issues, such as varicosities, ulcers, and diabetic microangiopathy; and (3) cognitive dysfunction, integrative oncology, and toxic metal chelation.

Several experimental and clinical studies support topical use of gotu kola as a wound-healing and cicatrizing agent. ^6-8A tertiary review (Cochrane) examined trials of topical preparations for striae gravidarum and found at least one combination preparation had significant results for this condition. ⁹ Although the underlying mechanisms for this activity have not been fully elucidated, recent experimental data suggest effects on fibroblast gene expression modulating connective tissue matrix formation and angiogenesis, including by fibroblast growth factor. ^10,11This is consistent with previous animal studies that showed increases in collagen strength and extracellular matrix collagen content in animal wound-healing models, although the involvement of an antioxidant mechanism is also possible. ^6,7,12,13The mechanisms of wound healing suggest that combinations with nutritional and herbal agents directed toward promotion of wound healing are likely to be a fruitful area of interaction research. For example, Cesarone, Belcaro, Incandela, De Sanctis, and others have conducted numerous small clinical trials with oral gotu kola extracts (particularly Centellase, a preparation standardized to 40% asiaticosides, 30% madecassic acid, 30% asiatic acid) for venous insufficiency, varicose veins, and diabetic microangiopathy, with positive results. ^14-23The Cochrane review of trials of topical preparations for treatment of striae gravidarum found that the most effective preparation was a combination product in which the centella extract was combined with α-tocopherol and collagen hydrolysates, suggesting that the combination with vitamin E was more effective than preparations based on the herb alone. ⁹

Adaptogenic herbs such as the ginsengs (e.g., Panax ginseng C.A. Meyer) have been incorporated in several ways into integrative cancer protocols. Evidence for possible roles for gotu kola interacting with conventional treatments in the integrative oncological environment is limited, however, and its use needs to be approached with caution. Discounting antiproliferative effects on keratinocytes in psoriasis, few studies show direct cytotoxic effects on cell lines (Ehrlich ascites and Dalton's lymphoma ascites, MCF-7 and MDA-MB231 breast cancer) and in vivo (mouse lung fibroblast) models. ^24,25

One caveat for use of gotu kola in the oncology setting is that the wound-healing activity of the herb is associated with promotion of angiogenesis. ¹¹ Arguably, in metastatic disease treated with antiangiogenic agents, theoretical antagonism with these agents, such as bevacizumab (Avastin), is possible. Many antiangiogenic drugs are investigational at present but are likely to expand significantly as a drug class in the near future.

Oral extracts of gotu kola appear to have potential for protection against radiation-induced dermatitis in animal models, as well as for reduction of radiation-induced changes in taste-related behavior and protection of healthy cells against damage by radiation. ^26-29

Combinations with cytotoxic chemotherapeutic drugs have recently been investigated in a few experimental studies. In a colon cancer line, asiatic acid dose-dependently synergized with irinotecan (CPT-11). ³⁰ Oral pretreatment with Centella asiatica ameliorated doxorubicin-induced cardiomyopathy in a rodent model. ³¹

In another study, asiaticoside enhanced the cytotoxicity of vincristine in four cell lines. ³² Such data are preliminary, but taken together with the general antioxidant, neuroprotective, and immunomodulating properties of the herb, suggest promise for its possible incorporation into integrative oncological protocols.

There are few leads to suggest mechanisms of neurocognitive pharmacology of gotu kola, despite its traditional reputation for cognitive enhancement and as a longevity tonic. ^33,34In vitro the herb appears to promote neurite growth andve egeneration. ³⁵ Experimental studies suggest some modulation of streptozocin-induced “models” of Alzheimer's disease, ³⁶ and semisynthetic asiaticoside derivatives have been tested positively against beta-amyloid neurotoxicity. ³⁷ Centella extracts may protect against glutamate-induced excitotoxicity in cortical neuron culture systems, an effect considered to be mediated by antioxidant mechanisms. ³⁸ Modulation of the acoustic startle responses in rodents (resembling similar effects induced by anxiolytic drugs) has been demonstrated after oral administration of the extracts and is thought to be mediated by a cholecystokinin (CCK) mechanism. ^39,40Another rodent study examined the effect of oral gotu kola on the course of kindling development, kindling-induced learning deficit, and oxidative stress markers in pentylenetetrazole (PTZ)–induced kindling in rats. The authors suggested a possible interaction role for combining gotu kola with antiepileptic medications to help prevent kindling-promoted learning deficits. ⁴¹

At present the available data, mostly derived from in vitro and animal tests, are not sufficiently coherent for a meaningful analysis of potential interactions with psychiatric or neurological drugs. Nonetheless, research in the role of gotu kola extracts in neurocognitive conditions may lead to their use in psychopharmacological integrative strategies as more data become available.

• 1.Frawley D, Lad V. The Yoga of Herbs. Twin Lakes, Wis: Lotus Press; 1988.
• 2.BHMA. Centella. British Herbal Pharmacopoeia. Bournemouth, UK: British Herbal Medicine Association; 1983:56-57.
• 3.WHO. Herba Centellae. WHO Monographs on Selected Medicinal Plants. 1 vol. Geneva: World Health Organization; 1999:77-85.
• 4.Newall C, Anderson L, Phillipson J. Hydrocotyle. Herbal Medicines. London: Pharmaceutical Press; 1996:170-172.
• 5.Gotu kola. In: Jellin J, Gregory P, Batz F et al, eds. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. 3rd ed. Stockton, Calif: Therapeutic Research Faculty; 2000:508-510.
• 6.Maquart FX, Chastang F, Simeon A et al. Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur J Dermatol 1999;9:289-296.View Abstract
• 7.Shukla A, Rasik AM, Jain GK et al. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol 1999;65:1-11.View Abstract
• 8.Widgerow AD, Chait LA, Stals R, Stals PJ. New innovations in scar management. Aesthetic Plast Surg 2000;24:227-234.View Abstract
• 9.Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev (Online: Update Software) 2000:CD000066.View Abstract
• 10.Coldren CD, Hashim P, Ali JM et al. Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids. Planta Med 2003;69:725-732.View Abstract
• 11.Cheng CL, Guo JS, Luk J, Koo MWL. The healing effects of Centella extract and asiaticoside on acetic acid–induced gastric ulcers in rats. Life Sci 2004;74:2237-2249.
• 12.Shukla A, Rasik AM, Dhawan BN. Asiaticoside-induced elevation of antioxidant levels in healing wounds. Phytother Res 1999;13:50-54.View Abstract
• 13.Hamid AA, Shah ZM, Muse R, Mohamed S. Characterisation of antioxidative activities of various extracts of Centella asiatica (L) Urban. Food Chem 2002;77:465-469.
• 14.Cesarone MR, Belcaro G, De Sanctis MT et al. Effects of the total triterpenic fraction of Centella asiatica in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial. Angiology 2001;52:S15-S18.View Abstract
• 15.Cesarone MR, Belcaro G, Nicolaides AN et al. Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial. Angiology 2001;52:S19-S25.View Abstract
• 16.Cesarone MR, Incandela L, De Sanctis MT et al. Flight microangiopathy in medium- to long-distance flights: prevention of edema and microcirculation alterations with total triterpenic fraction of Centella asiatica. Angiology 2001;52:S33-S37.View Abstract
• 17.Cesarone MR, Belcaro G, Rulo A et al. Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO₂-CO₂, and leg volumetry. Angiology 2001;52:S45-S48.
• 18.Cesarone MR, Incandela L, De Sanctis MT et al. 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:S49-S54.View Abstract
• 19.De Sanctis MT, Belcaro G, Incandela L et al. Treatment of edema and increased capillary filtration in venous hypertension with total triterpenic fraction of Centella asiatica: a clinical, prospective, placebo-controlled, randomized, dose-ranging trial. Angiology 2001;52:S55-S59.View Abstract
• 20.Incandela L, Belcaro G, Cesarone MR et al. Treatment of diabetic microangiopathy and edema with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled randomized study. Angiology 2001;52:S27-S31.View Abstract
• 21.Incandela L, Belcaro G, De Sanctis MT et al. Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model. Angiology 2001;52:S61-S67.View Abstract
• 22.Incandela L, Belcaro G, Nicolaides AN et al. Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, randomized, placebo-controlled trial. Angiology 2001;52:S69-S73.View Abstract
• 23.Incandela L, Cesarone MR, Cacchio M et al. Total triterpenic fraction of Centella asiatica in chronic venous insufficiency and in high-perfusion microangiopathy. Angiology 2001;52:S9-13.View Abstract
• 24.Babu TD, Kuttan G, Padikkala J. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) Urban. J Ethnopharmacol 1995;48:53-57.View Abstract
• 25.Hsu YL, Kuo PL, Lin LT, Lin CC. Asiatic acid, a triterpene, induces apoptosis and cell cycle arrest through activation of extracellular signal–regulated kinase and p38 mitogen–activated protein kinase pathways in human breast cancer cells. J Pharmacol Exp Ther 2005;313:333-344.View Abstract
• 26.Chen YJ, Dai YS, Chen BF et al. The effect of tetrandrine and extracts of Centella asiatica on acute radiation dermatitis in rats. Biol Pharm Bull 1999;22:703-706.View Abstract
• 27.Shobi V, Goel HC. Protection against radiation-induced conditioned taste aversion by Centella asiatica. Physiol Behav 2001;73:19-23.View Abstract
• 28.Sharma J, Sharma R. Radioprotection of Swiss albino mouse by Centella asiatica extract. Phytother Res 2002;16:785-786.View Abstract
• 29.Sharma R, Sharma J. Modification of gamma ray–induced changes in the mouse hepatocytes by Centella asiatica extract: in vivo studies. Phytother Res 2005;19:605-611.View Abstract
• 30.Bunpo P, Kataoka K, Arimochi H et al. Inhibitory effects of asiatic acid and CPT-11 on growth of HT-29 cells. J Med Invest 2005;52:65-73.View Abstract
• 31.Gnanapragasam A, Ebenezar KK, Sathish V et al. Protective effect of Centella asiatica on antioxidant tissue defense system against Adriamycin-induced cardiomyopathy in rats. Life Sci 2004;76:585-597.View Abstract
• 32.Huang Y-H, Zhang S-H, Zhen R-X et al. [Asiaticoside inducing apoptosis of tumor cells and enhancing anti-tumor activity of vincristine.]. Ai Zheng 2004;23:1599-1604.View Abstract
• 33.Howes MJ, Houghton PJ. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacol Biochem Behav 2003;75:513-527.View Abstract
• 34.Howes M-JR, Perry NSL, Houghton PJ. Plants with traditional uses and activities, relevant to the management of Alzheimer’s disease and other cognitive disorders. Phytother Res 2003;17:1-18.
• 35.Saxena G, Flora SJS. Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead-poisoned rats. J Pharm Pharmacol 2006;58:547-559.
• 36.Veerendra Kumar MH, Gupta YK. Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer’s disease in rats. Clin Exp Pharmacol Physiol 2003;30:336-342.
• 37.Jew S-S, Yoo C-H, Lim D-Y et al. Structure-activity relationship study of asiatic acid derivatives against beta amyloid (A beta)–induced neurotoxicity. Bioorg Med Chem Lett 2000;10:119-121.View Abstract
• 38.Lee MK, Kim SR, Sung SH et al. Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Res Commun Mol Pathol Pharmacol 2000;108:75-86.View Abstract
• 39.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. J Clin Psychopharmacol 2000;20:680-684.View Abstract
• 40.Harro J, Vasar E, Bradwejn J. CCK in animal and human research on anxiety. Trends Pharmacol Sci 1993;14:244-249.View Abstract
• 41.Gupta YK, Veerendra Kumar MH, Srivastava AK. Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav 2003;74:579-585.View Abstract
• 42.Chatterjee TK, Chakraborty A, Pathak M, Sengupta GC. Effects of plant extract Centella asiatica (Linn.) on cold restraint stress ulcer in rats. Indian J Exp Biol 1992;30:889-891.View Abstract
• 43.Sairam K, Rao CV, Goel RK. Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats. Indian J Exp Biol 2001;39:137-142.View Abstract
• 44.Bone K. Gotu kola. A Clinical Guide to Blending Liquid Herbs. St Louis: Churchill Livingstone; 2003.
• 45.Gotu kola (Centella asiatica Linn. and total triterpene fraction of Centella asiatica [TTFCA]). Accessed June 2002 at www.natural standard.com/monographs/herbssupplements/gotukola.asp: Natural Standard; 2001.