Gotu Kola

• How It Works

  Only a few studies suggest that gotu kola may be helpful for wound healing or poor circulation. Larger studies that confirm such results are needed.

  Gotu kola is a plant that contains many biologically active compounds. Although this botanical is popular in traditional medicines, it has mostly been studied in the lab. A variety of properties have been described, including improved wound healing and anti-inflammatory effects.

  Only a few studies of gotu kola have been conducted in humans. Some data suggest that it can decrease venous pressure in people with venous insufficiency, speed wound healing, relieve anxiety, or improve cognition. However, there is insufficient evidence to support its use for any of these conditions.

• Purported Uses
  • To lower high blood pressure
    Several clinical trials suggest that gotu kola can reduce venous hypertension in patients with chronic venous insufficiency, but there is no evidence that this herb can treat typical (arterial) high blood pressure.
  • To treat chronic venous insufficiency
    Several clinical trials suggest benefit.
  • To treat wounds or burns
    Only a few lab and human studies suggest that gotu kola aids in wound healing and may reduce inflammation. Additional studies are needed.
  • To improve cognitive function
    A preliminary study suggests benefit, but a meta-analysis did not find strong enough evidence to support the use of gotu kola for cognitive function improvement. Larger well-designed studies are needed.
• Do Not Take If
  • You are taking drugs that are substrates of cytochrome P450 1A2, 2C9, 2D6, 3A4, and 2C19 enzymes: Lab studies suggest that gotu kola may increase the risk of side effects of these drugs. Clinical relevance has yet to be determined.
• Side Effects
  • Skin rash
  • Liver toxicity
• Special Point
  • Gotu kola should not be confused with kolanut. Gotu kola does not contain caffeine and has not been shown to have stimulant properties.
  • Depending on where gotu kola is grown, the amount of active compounds in this herb can vary widely.
• Scientific Name

  Centella asiatica, Hydrocotyle asiatica

• Clinical Summary

  Gotu kola is an evergreen perennial plant that is prevalent in East Asia and many parts of South Africa. Extracts from the leaf and the whole plant are used for a variety of conditions including venous insufficiency, varicose veins, wound healing, scleroderma, and scars. In vitro and in vivo analyses indicate that gotu kola has neuroprotective ⁽¹³⁾ and chemopreventive ^(14) (19) properties, and also protects against cognitive impairment ⁽²⁰⁾. Other laboratory studies suggest the active constituent madecassoside has antiarthritic ⁽⁵⁾ and cardioprotective properties ⁽⁴⁾ and that topical application of an asiaticoside extracted from gotu kola may enhance burn wound healing ⁽⁶⁾.

  Only a few studies have been conducted in humans. Data show a reduction in lower extremity edema with gotu kola compared to placebo in patients with chronic venous insufficiency ^{(1) (2) (3)}. With respect to wounds, one study suggests an oral extract may speed healing in diabetic patients ⁽²²⁾. In another study, treatment with a topical gotu kola ointment improved both objective and subjective symptoms in burn wound patients compared with silver sulfadiazine ⁽²⁹⁾. A few small studies suggest that supplementation with gotu kola improved cognitive function and mood in the elderly ⁽⁷⁾, and alleviated generalized anxiety disorder ⁽¹⁶⁾, although a meta-analysis did not find strong enough evidence to support the use of gotu kola for cognitive function improvement ⁽³⁰⁾. Larger well-designed studies are needed to confirm these effects.

  Gotu kola should not be confused with kolanut. Gotu kola does not contain any caffeine and has not been shown to have stimulant properties.

• Purported Uses
  • Circulatory disorders
  • Wound healing
  • Memory loss
• Mechanism of Action

  Triterpenoids have been identified as active constituents in gotu kola. Asiaticoside demonstrates anti-inflammatory effects by inhibiting lipopolysaccharide-induced fever and inflammatory response, including production of serum tumor necrosis factor-alpha, interleukin-6, prostaglandin E(2), liver myeloperoxidase activity, and expression of brain cyclooxygenase-2 protein ⁽²³⁾. Asiaticoside also promotes wound healing by stimulating collagen and glycosaminoglycan synthesis, and angiogenesis ⁽⁶⁾. Another study showed that a gotu kola extract may regulate stress-induced premature senescence by preventing repression of DNA replication and mitosis-related gene expression ⁽²⁴⁾.

  A water extract of gotu kola prevented the formation of intracellular beta-amyloid aggregates in a mouse model of Alzheimer’s disease with high amounts of beta-amyloid ⁽²⁵⁾.

• Adverse Reactions
  • Contact dermatitis ⁽¹⁷⁾; hepatotoxicity ^(18) (26)
• Herb-Drug Interactions
  • Cytochrome P450 substrates: In vitro studies suggest gotu kola inhibits CYP 1A2, 2C9, ⁽³¹⁾ CYP 2D6, CYP 3A4 ⁽²¹⁾ and CYP 2C19 ⁽²⁷⁾ and may affect the intracellular concentration of drugs metabolized by these enzymes. Clinical relevance has yet to be determined.
• References

  1. Cesarone MR, 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.

  2. Cesarone MR, 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.

  3. Pointel JP, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiology 1987;38:46-50.

  4. Bian GX, Li GG, Yang Y, et al. Madecassoside reduces ischemia-reperfusion injury on regional ischemia induced heart infarction in rat.Biol Pharm Bull. Mar 2008;31(3):458-463.

  5. Liu M, Dai Y, Yao X, et al. Anti-rheumatoid arthritic effect of madecassoside on type II collagen-induced arthritis in mice. Int Immunopharmacol. Nov 2008;8(11):1561-1566.

  6. Kimura Y, Sumiyoshi M, Samukawa K, et al. Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism. Eur J Pharmacol. Apr 28 2008;584(2-3):415-423.

  7. Wattanathorn J, Mator L, Muchimapura S, et al. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol. Mar 5 2008;116(2):325-332.

  8. Newall CA, et al. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press; 1996.

  9. DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999.

  10. Bradwein J, et al. 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.

  11. Klovekorn W, Tepe A, Danesch U. A randomized, double-blind, vehicle-controlled, half-side comparison with a herbal ointment containing Mahonia aquifolium, Viola tricolor and Centella asiatica for the treatment of mild-to-moderate atopic dermatitis. Int J Clin Pharmacol Ther. Nov 2007;45(11):583-591.

  12. Dutta T, Basu UP. Crude extract of Centella Asiatica & Products Derived from Its Glycosides as Oral Antifertility Agents. Indian J Exp Biol. 1968;(6):181-182.

  13. Shinomol GK, Muralidhara. Prophylactic neuroprotective property of Centella asiatica against 3-nitropropionic acid induced oxidative stress and mitochondrial dysfunctions in brain regions of prepubertal mice. Neurotoxicology. 2008 Nov;29(6):948-57.

  14. Bunpo P, Kataoka K, Arimochi H, et al. Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt focus formation and carcinogenesis in the intestines of F344 rats. Food Chem Toxicol. 2004 Dec;42(12):1987-97.

  15. Sastravaha G, Gassmann G, Sangtherapitikul P, Grimm WD. Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts in supportive periodontal therapy. J Int Acad Periodontol. 2005 Jul;7(3):70-9.

  16. Jana U, Sur TK, Maity LN, Debnath PK, Bhattacharyya D. A clinical study on the management of generalized anxiety disorder with Centella asiatica. Nepal Med Coll J. 2010 Mar;12(1):8-11.

  17. Gomes J, Pereira T, Vilarinho C, Duarte Mda L, Brito C. Contact dermatitis due to Centella asiatica. Contact Dermatitis. 2010 Jan;62(1):54-5.

  18. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig. 2005 Feb;97(2):115-24.

  19. Tang XL, Yang XY, Jung HJ, et al. Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade. Biol Pharm Bull. 2009 Aug;32(8):1399-405.

  20. Kumar A, Prakash A, Dogra S. Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice. Int J Alzheimers Dis. 2011;2011:347569.

  21. Pan Y, Abd-Rashid BA, Ismail Z, et al. In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica. J Ethnopharmacol. 2010 Jul 20;130(2):275-83.

  22. Paocharoen V. The efficacy and side effects of oral Centella asiatica extract for wound healing promotion in diabetic wound patients. J Med Assoc Thai. 2010 Dec;93 Suppl 7:S166-70.

  23. Wan J, Gong X, Jiang R, Zhang Z, Zhang L. Antipyretic and Anti-inflammatory Effects of Asiaticoside in Lipopolysaccharide-treated Rat through Up-regulation of Heme Oxygenase-1. Phytother Res. 2012 Sep 12. doi: 10.1002/ptr.4838. [Epub ahead of print]

  24. Kim YJ, Cha HJ, Nam KH, et al. Centella asiatica extracts modulate hydrogen peroxide-induced senescence in human dermal fibroblasts. Exp Dermatol. 2011 Dec;20(12):998-1003.

  25. Soumyanath A, Zhong YP, Henson E, et al. Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer’s Disease: Investigation of a Possible Mechanism of Action. Int J Alzheimers Dis. 2012;2012:381974.

  26. Dantuluri S, North-Lewis P, Karthik SV.Gotu Kola induced hepatotoxicity in a child – need for caution with alternative remedies. Dig Liver Dis. 2011 Jun;43(6):500.

  27. Pan Y, Abd-Rashid BA, Ismail Z, et al. In vitro modulatory effects of Andrographis paniculata, Centella asiatica and Orthosiphon stamineus on cytochrome P450 2C19 (CYP2C19). J Ethnopharmacol. 2011 Jan 27;133(2):881-7.

  28. Gohil KJ, Patel JA, Gajjar AK. Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all. Indian J Pharm Sci. 2010 Sep;72(5):546-56.

  29. Saeidinia A, Keihanian F, Lashkari AP, et al. Partial-thickness burn wounds healing by topical treatment: A randomized controlled comparison between silver sulfadiazine and centiderm. Medicine (Baltimore). Mar 2017;96(9):e6168.

  30. Puttarak P, Dilokthornsakul P, Saokaew S, et al. Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis. Sci Rep. Sep 6 2017;7(1):10646.

  31. Savai J, Varghese A, Pandita N, et al. In vitro assessment of CYP1A2 and 2C9 inhibition potential of Withania somnifera and Centella asiatica in human liver microsomes. Drug Metab Pers Ther. Jun 2015;30(2):137-141.