Dr Clare Materia Medica

Gotu Kola

Also Known As:

Brahma-Buti, Brahma-Manduki, Brahmi, Centella, Centella Asiática, Centella Asiatique, Centellase, Divya, Hydrocotyle, Hydrocotyle Asiatique, Hydrocotyle Indien, Indischer Wassernabel, Idrocotyle, Indian Pennywort, Indian Water Navelwort, Ji Xue Cao, Khulakhudi, Luei Gong Gen, Luo De Da, Madecassol, Mandukaparni, Manduk Parani, Mandukig, Marsh Penny, TTFCA, Talepetrako, Thick-Leaved Pennywort, Tsubo-kusa, Tungchian, White Rot.

CAUTION: See separate listings for Brahmi and Cola Nut.

Scientific Name:

Centella asiatica, synonym Hydrocotyle asiatica; Centella coriacea.

Family: Apiaceae/Umbelliferae.

People Use This For:

Orally, gotu kola is used for reducing fatigue, anxiety, depression, improving memory and intelligence, Alzheimer's disease, venous insufficiency including varicose veins, wound healing, and increasing longevity.

It is also used for the common cold and influenza, swine flu, sunstroke, tonsillitis, pleurisy, urinary tract infection (UTI), hepatitis, jaundice, abdominal pain,diarrhoea, indigestion, gastritis, peptic ulcer disease, dysentery, trauma, shingles,leprosy, cholera, syphilis, psychiatric disorders, epilepsy, asthma, anaemia, and diabetes. Gotu kola is also used for contraception, amenorrhea, elephantiasis, systemic lupus erythematosus (SLE), tuberculosis, memory loss, and as an aphrodisiac. Topically, gotu kola is used for wound healing and reducing scars. Parenterally, gotu kola is used for bladder lesions associated with schistosomiasis.

Safety:

POSSIBLY SAFE ...when used topically and appropriately.

Gotu kola has been used safely in a cream and ointment for up to 8weeks (27, 28). ...when used

orally. Gotu kola has been used safely in trials lasting up to 12 months (7, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26). However, there is concern that gotu kola might cause hepatotoxicity in some

patients (29). PREGNANCY: POSSIBLY SAFE ...when used topically and appropriately (28, 31). There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.

LACTATION: Insufficient reliable information available; avoid using.

Effectiveness:

POSSIBLY EFFECTIVE

Venous insufficiency. Taking gotu kola orally for 4-8 weeks seems to improve measures of circulation and decrease symptoms such as edema (7, 11, 18, 19, 21, 25).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Atherosclerosis. There is preliminary evidence that taking gotu kola orally for 12 months might help stabilize low-density atherosclerotic plaques. Stabilizing these plaques might reduce the risk of rupture and embolism (17,24).

Deep vein thrombosis (DVT). Gotu kola helps prevent thrombosis related to long-distance flights.Preliminary evidence suggests that gotu kola might decrease edema, and improve measures of circulation in patients traveling on airplanes for more than 3 hours (22); however, it is not known if t

his actually results in a decreased incidence of clots. Diabetic microangiopathy. Taking gotu kola orally for 6-12 months might help increase measures of circulation, and decrease edema in patients with diabetic microangiopathy (20, 23).

Keloids. There is some evidence that applying an extract of gotu kola, known as madecassol, topically might help reduce keloids and hypertrophic scarring (30).

Psoriasis. Some evidence suggests that applying gotu kola topically might help reduce symptoms of psoriasis (6).

Scarring: Preliminary evidence suggests that applying a specific gotu kola cream (Alpha centella, not available in the US) twice daily for 6-8weeks following suture removal might help reduce scarring in patients without a history of keloid formation (27).

Schistosomiasis. There is some evidence that using gotu kola parenterally might help bladder lesions of schistosomiasis (bilharzial infections) (10).

Stretch marks (striae gravidarum). Preliminary evidence suggests that applying a specific mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates in a cream (Trofolastin, not available in the US) daily during the second and third trimesters of pregnancy until labor might reduce stretch marks (31). There is also preliminary evidence that another specific mixture of gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol in an ointment (Verum, not available in the US) might help decrease the formation of stretch marks during pregnancy (28).

Wound healing. Preliminary evidence suggests that applying gotu kola topically might help improve wound healing (7). More evidence is needed to rate gotu kola for these uses.

Mechanism of Action:

The applicable parts of gotu kola are the above groundparts. The primary constituents responsible for the pharmacological effects are thought to be the saponin-containing triterpene acids, 1% to 8%; and their sugar esters, including asiatic acid, madecassic acid, asiaticoside A (madecassoside), and asiaticoside B (26). Gotu kola also contains essential oils; flavonoids; and flavone derivatives  including quercetin and kaempferol, sesquiterpenes, stigmasterol, sitosterol, and isothankuniside (713).

In vitro evidence suggests that gotu kola might bind cholecystokinin (CCK) and GABA receptors, which might be responsible for reported anxiolytic effects of gotu kola (6, 26). The effects on GABA might also results in sedative, anticonvulsant, and analgesic effects (7). There is some evidence that taking gotu kola orally might to reduce the startle response in healthy volunteers (26).

Some researchers think the asiaticoside derivatives, asiatic acid, asiaticoside 6, and SM2, might have a role in Alzheimer's disease. Preliminary evidence that they might protect neurons from beta-amyloid toxicity (3).

The triterpenoid saponins (e.g., asiaticoside, madecassoside) seem to increase wound healing and decrease venous pressure in venous insufficiency (2. 5, 11). Asiaticoside and other terpenoids might have anti-inflammatory activity (27, 32). The terpenoid extract seems to improve connective tissue re

modeling by increasing fibroblast activity, stimulating collagen synthesis, increasing epithelial turnover over, and decreasing capillary permeability (16,17,19). Gotu kola is thought to increase the production of type I collagen in scar formation over type II. Type II collagen is associated with hypertrophic scarring (27).

The terpenoid extract might help stabilize arterial plaques by increasing collagen within plaques. Plaques with low collagen content are structurally weak and are associated with an increased risk of rupture and embolism (17, 24)). There is also some evidence that asiaticosides might promote wound healing by stimulating collagen and glycosaminoglycan synthesis (4, 5). There's preliminary evidence that asiaticosides might also have preventive and therapeutic effects on gastrointestinal ulcers (7, 8). Anti-ulcer mechanisms may be due to strengthening action on gastric mucosal lining and suppression of damaging effects of free radicals (8).

Preliminary evidence suggests that purified isothankuniside might decrease fertility. However, a crude extract of gotu kola does not reduce fertility (13). Gotu kola extracts also seem to have antibacterial activity in vitro against Pseudomonas pyocyaneus, Trichoderma mentagrophytes, and Entamoeba histolytica. It also seems to have antiviral activity againstHerpes simplex type II (7).

There is some interest in using gotu kola to treat cancer. Dried powder extracts of gotu kola exhibit cytotoxic and anti-tumor properties in preliminary studies.

Normal lymphocytes are not harmed, which suggests gotu kola exerts selective toxicity towards tumor cells (9).

There are some case reports of hepatotoxicity. The triterpenoids contained in gotu kola are theorized to be responsible for this adverseeffect (29).

Adverse Reactions:

Orally, gotu kola is usually well-tolerated when used in typical doses (17, 18, 19, 20, 22, 23, 24, 25, 26). However, in some patients it can cause gastrointestinal upset and nausea (7). Theoretically, gotu kola might also cause drowsiness (7). There are at least three cases of hepatotoxicity associated with gotu kola. In one case, a 61-year-old woman developed elevated liver function tests (LFTs) including AST, ALT, alkaline phosphatase, and total bilirubin after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis, suggesting an immune mediated hepatitis. LFTs improved when gotu kola was discontinued. Months later the patient took gotu kola again and developed elevated LFTs again after 2 weeks. In another case, a 52-year-old woman developed symptoms of hepatitis and increased LFTs after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas,areas of necrosis, and cirrhotic transformation. LFTs normalized after discontinuation of gotu kola.

In a third case, a 49-year-old woman developed symptoms of hepatitis and elevated LFTs 2 months after starting gotu kola. Biopsy revealed granulomatous hepatitis. LFTs normalized after discontinuation of gotu kola (27). Researchers did not perform laboratory analysis of the products taken in these cases to determine if they were free of hepatotoxic contaminants. Therefore, it is not

possible to rule out product contamination. The doses of gotu kola taken by these patients is unknown. Therefore, it is not known if higher doses are more likely than lower doses to cause hepatotoxicity. In a clinical trial where liver function was monitored, patients taking gotu kola 120 mg/day for 6 months, no changes in hepatic function were observed (20).

Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (1,7, 12). Gotu kola may also cause eczema when applied topically (14, 15).

Interactions with Herbs & Supplements:

HEPATOTOXIC HERBS AND SUPPLEMENTS: There is some concern that gotu kola might cause hepatotoxicity in some patients (29). Theoretically, concomitant use with other potentially hepatotoxic products might increase the risk of developing liver damage. Some of these products include

androstenedione, chaparral, comfrey, DHEA, germander, niacin, pennyroyaloil, red yeast, and others.

HERBS AND SUPPLEMENTS WITH SEDATIVE PROPERTIES: Theoretically, concomitant use with herbs that have sedative properties might enhance therapeutic and adverse effects (7). Some of these supplements include 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John's wort, skullcap, valerian, yerba mansa, and others.

Interactions with Drugs:

Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (1,7, 12). Gotu kola may also cause eczema when applied topically (14, 15).

Interactions with Herbs & Supplements:

HEPATOTOXIC HERBS AND SUPPLEMENTS: There is some concern that gotu kola might cause hepatotoxicity in some patients (29). Theoretically, concomitant use with other potentially hepatotoxic products might increase the risk of developing liver damage. Some of these products include androstenedione, chaparral, comfrey, DHEA, germander, niacin, pennyroyal oil, red yeast, and others.

HERBS AND SUPPLEMENTS WITH SEDATIVE PROPERTIES: Theoretically, concomitant use with herbs that have sedative properties might enhance therapeutic and adverse effects (7). Some of these supplements include 5-HTP, calamus, California poppy, catnip, hops, Jamaican dogwood,kava, St. John's wort, skullcap, valerian, yerba mansa, and others.

Interactions with Drugs:

CNS DEPRESSANTS <<interacts with>> GOTU KOLA

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Probable • Level of Evidence = D

Theoretically, concomitant use of gotu kola with drugs with sedative properties might cause additive effects and side effects (7). Some sedative drugs include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem  (Ambien), and others.

HEPATOTOXIC DRUGS <<interacts with>> GOTU KOLA

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

There is some concern that gotu kola might cause hepatotoxicity in some  patients (29). Theoretically, concomitant use with other potentially hepatotoxic drugs might increase the risk of developing liver damage. Some of these drugs include acarbose (Precose, Prandase), amiodarone (Cordarone), atorvastatin (Lipitor), azathioprine (Imuran), carbamazepine (Tegretol), cerivastatin (Baycol), diclofenac (Voltaren), felbamate (Felbatol), fenofibrate (Tricor), fluvastatin (Lescol), gemfibrozil (Lopid), isoniazid, itraconazole, (Sporanox), ketoconazole (Nizoral), leflunomide (Arava), lovastatin (Mevacor), methotrexate (Rheumatrex), nevirapine (Viramune), niacin, nitrofurantoin (Macrodantin), pioglitazone (Actos), pravastatin (Pravachol), pyrazinamide, rifampin (Rifadin), ritonavir (Norvir), rosiglitazone (Avandia), simvastatin (Zocor), tacrine (Cognex), tamoxifen, terbinafine (Lamisil), valproic acid, and zileuton (Zyflo).

Interactions with Foods:

None known.

Interactions with Lab Tests:

None known.

Interactions with Diseases or Conditions:

LIVER DISEASE: There is concern that gotu kola might be linked to cases of hepatotoxicity (29). Theoretically, gotu kola might exacerbate liver problems in patients with existing liver disease such as hepatitis. Advise these patients to avoid taking gotu kola.

SURGERY: Gotu kola has CNS depressant effects. Theoretically, gotu kola might cause additive CNS depression when combined with anesthesia and other medications during and after surgical procedures. Tell patients to discontinue gotu kola at least 2 weeks before elective surgical procedures.

Dosage/Administration:

ORAL: For atherosclerosis, 60 mg of gotu kola extract three times daily has been used (17, 24). For diabetic microangiopathy, 60 mg of gotu kola extract twice daily has been used (20, 23). For venous insufficiency, 60-180 mg daily of gotu kola extract has been used (18, 19, 21, 25). For deep vein thrombosis (DVT) prevention while flying, 120 mg of gotu kola extract 3 days before the flight, the day of the flight, and the day after have been used (22).

TOPICAL: For wound healing, 1% gotu kola creams have been used (7). For scars, gotu kola has been used in combination with the extract from Bulbine frutescens (Alpha centella cream, not available in the US) for 6-8weeks (27).

For preventing stretch marks in pregnancy, gotu kola has been used in combination with several other ingredients (Trofolastin and Verum). Trofolastin cream (not available in the US) is a mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates (21). Verum ointment (not availablein the US) contains gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol (28).

Editor's Comments:

Gotu kola is a commonly used herb in Tradition Chinese and Ayurvedic medicine (26). The terpenoid extract of gotu kola is sometimes referredto as TTFCA (total terpenoid fraction of Centella asiatica) and Centellase. Avoid confusion with cola nut (Cola acuminata), and swamp pennywort (Centella cordifolia). Centella cordifolia is often misidentified as Centella asiatica (gotu kola).

Specific References:

1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

2. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiol 161 1987;38:46-50.

3. Mook-Jung I, Shin JE, Yun SH, et al. Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity. J Neurosci Res 1999;58:417-25.

4. Maquart FX, Chastang F, Simeon A, et al. Triterpenes from Centella asiatica stimulate extracellular matrix accumulation in rat experimental wounds. Eur J Dermatol 1999;9:289-96.

5. 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.

6. Kenady DE, Chretien PB, Potvin C, Simon RM. Thymosin reconstitution of T-cell deficits in vitro in cancer patients. Cancer 1977;39:575-80.

7. Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the east Asian medical plant Centella asiatica. Phytomedicine 2000;7:427-48.

8. Cheng CL, Koo MWL. Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats. Life Sci 2000;67:2647-53.

9. Babu TD, Kuttan G, Padikkala J. Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference toCentella asiatica (L.) Urban. J Ethnopharmacol 1995;48:53-7.

10. Fam A. Use of titrated extract of Centella asiatica (TECA) in bilharzial bladder lesions. Int Surg 1973;58:451-2.

11. Belcaro GV, Rulo A, Grimaldi R. Capillary filtration and ankle edema in patients with venous hypertension treated with TTFCA. Angiology 1990;41:12-8.

12. Eun HC, Lee AY. Contact dermatitis due to madecassol. Contact Dermatitis 1985;13:310-3.

13. Dutta T, Basu UP. Crude extract of Centella asiatica and products derived from its glycosides as oral antifertility agents. Indian J Exp Biol 1968;6:181-2.

14. Hausen BM. Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer. Contact Dermatitis 1993;29:175-9.

15. Bilbao I, Aguirre A, Zabala R, et al. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract.Contact Dermatitis 1995;33:435-6.

16. 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 Suppl 2:S913.

17. 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 Suppl 2:S69-73.

18. 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 Suppl 2:S61-7.

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 Suppl 2:S55-9

20. 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 Suppl 2:S49-54.

21. 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 163 2001;52 Suppl 2:S45-8.

22. 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 Suppl 2:S33-7.

23. 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 Suppl 2:S27-31.

24. 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 Suppl 2:S19-25.

25. 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 Suppl 2:S15-18.

26. 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;20:680-4.

27. Widgerow AD, Chait LA, Stals R, Stals PJ. New innovations in scar management. Aesthetic Plast Surg 2000;24:227-34.

28. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev 2000;(2):CD000066.

29. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005;97:115-24.

30. Bosse JP, Papillon J, Frenette G, et al. Clinical study of a new antikeloid agent. Ann Plast Surg 1979;3:13,21.

31. Mallol J, Belda MA, Costa D, et al. Prophylaxis of striae gravidarum with a topical formulation. A double blind trial. Int J Cosmet Sci 1991;3:51-7.

32. Guo JS, Cheng CL, Koo MW. Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats. Planta Med 2004;70:1150-4.