Vol. 26:04

Gotu Kola

Gotu kola (Centella asiatica) is an important herb in Ayurvedic medicine, often mentioned in combination with the related European marsh pennywort (Hydrocotyle vulgaris). About 20 species related to Gotu kola grow in most parts of the tropic or wet pantropical areas such as rice paddies, and also in rocky, higher elevations.¹ Gotu kola, a perennial, is known by many names, including Indian pennywort, Brahmi, Chi-hsueh, Ts'ao, Talepetraco. In India, where Gotu kola is known as Brahmi (bringing knowledge of Brahman), it is widely used as a blood purifier as well as for treating a variety of other illnesses. It has been noticed by Sri Lankans that elephants munch on the leaves of Brahmi. It was believed that the leaves promoted longevity.¹ In Ayurveda, Brahmi is one of the chief herbs for revitalizing the nerves and brain cells. Eastern healers relied on Gotu kola to treat emotional disorders, such as depression, that were thought to be rooted in physical problems.^2,3 In Western medicine during the middle of the twentieth century, Gotu kola and its alcoholic extract showed positive results in the treatment of leprosy.⁴

Gotu kola is used to lower high blood pressure, improve memory and promote longevity. Gotu kola is very useful for people who are inactive or confined to bed due to illness. It improves blood flow while strengthening the veins and capillaries. As a mild diuretic, it can help to shrink swollen membranes and aid in the elimination of excess fluids. It reduces scarring when applied during the inflammatory period of a wound. It is also very effective on burns if applied immediately after the incident.

Chemical Composition and Pharmacology

The plant and its extract contain asiaticoside—an active principle of C. asiatica, in which a trisaccharide moiety is linked to the aglycone asiatic acid. The other triterpenoid derivative isolated from C. asiatica, also called madecassol, is a component of scar removal creams. These triterpene saponins and their sapogenins are mainly responsible for the wound healing and vascular effects. Other components isolated from C. asiatica, such as brahmoside and brahminoside, may be responsible for CNS and uterorelaxant actions, but are yet to be confirmed by clinical studies. Crude extract that contains isothankuniside and thankuniside showed antifertility action in mice.^5,6 Centelloside and its derivatives are found to be effective in the treatment of venous hypertension. In addition, the total extract contains plant sterols, flavonoids, and other components with no known pharmacological activity.

Medicinal and Other Uses of Gotu Kola

Wound Healing: The wound healing activity of asiaticoside was discovered and used during World War II. Since then, many clinical studies have supported that C. asiatica extract acts on certain cells of the epidermis and promotes keratinization and healing.⁷ Both in vivo clinical studies and human monolayer cell culture experiments have concluded that asiatic acid influences collagen synthesis, but no consensus has been reached about the efficacy of the extract or the selective action of the applied concentration of the triterpenoid fraction.^8,9 Other studies on wound healing actions emphasized the role of asiaticoside in the increased levels of antioxidants (enzymatic and nonenzymatic), which can be also responsible for accelerated wound healing.¹⁰ Angiogenesis plays an important role in wound healing since the newly formed blood vessels help the hypoxic wounds to attain normoxic conditions. Asiaticoside prompted angiogenesis in both in vivo and in vitro models.¹¹ In cases of vascular injury, thrombosis, acute myocardial infarction, and other peripheral vascular diseases, a higher number of circulating endothelial cells was detected. For example, in one study, patients with postphlebetic syndrome (PPS) showed an greater number of circulating endothelial cells compared to the normal subjects. During a three-week treatment with C. asiatica triterpenic fraction (CATF), PPS patients who received 90 mg CATF daily in three divided dosages showed a significant decrease (p<0.0001) in circulating endothelial cells, thereby indicating the effectiveness of >C. asiatica in protecting the integrity of vascular intima. The lower number of circulating endothelial cells could be attributed to the protective effect of CATF on vascular intima integrity.¹²

Effect on Varicose Veins: Titrated extract of C. asiatica (TECA) was tested on 94 patients suffering from venous insufficiency of the lower limbs. The patients were divided into three groups, each treated with TECA (120 mg/day, 60 mg/day or placebo) for two months. A significant difference (p<0.05) in favor of TECA groups was shown in the parameters checked for lower limbs and edema; also the overall evaluation was positive for the treated groups compared to the placebo.>¹³ CATF proved to be effective on microcirculation and capillary permeability.

Effect on Hypertension: Fifty-two patients with venous hypertension (pressure greater than 42 mmHg) were divided into three groups, each treated with 60 mg/day, 30 mg/day, or placebo. An additional 10 control subjects were treated with 60 mg/day. After four weeks of treatment significant improvements were observed in a concentration-dependent manner in the parameters tested, such as filtration rate, ankle edema, and ankle circumference. No significant change was observed in placebo and control subjects treated with CATF.¹⁴ In another double-blind clinical trial involving 87 patients with chronic venous hypertensive microangiopathy, two dosage forms of CATF (30 mg/day and 60 mg/day) were applied for 60 days and no unwanted effects were observed. The results also confirmed the efficacy of CATF in a dose-dependent manner.¹⁵ The effects of the CATFs on enzymes involved in mucopoly-saccharide metabolism supported the hypothesis that the extract acts on basic metabolism in the connective tissues of the vascular wall. The levels of basal serum uronic acid and enzymes involved in mucopolysaccharide metabolism (beta-glycuronidase, beta-N-acetylglucosaminidase, and arylsulfatase) were elevated in patients with varicose veins, indicating an increased muco-polysaccharide turnover. After treatment (60 mg/day for three months) the above enzyme levels fell progressively.¹⁶

Neuroprotective Effect: Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity were tested on B103 cell cultures and hypocampal slices. Out of 28 of the asiaticoside derivatives three components, including asiatic acid, showed a strong inhibition of beta-amyloid- and free radical-induced cell death. These derivatives may be candidates for a treatment of Alzheimer's disease that protects neurons from beta-amyloid toxicity.¹⁷

Anxiolytic Effect: Sedative and antianxiety properties of Gotu kola have been tested on small animals and are believed to be associated with its brahmoside and brahminoside constituents or saponin glycosides. ¹⁸

Antiulcer Effect: Animal studies showed that the extract of C. asiatica inhibited gastric ulceration, induced by cold and restraint stress, in rats. The antiulcer activity was compared to famotidine (H₂-antagonist) and sodium valproate (antiepleptic or antiseizure). Both the drugs and plant extract showed a dose-dependent reduction of gastric ulceration, which, except for the antiulcer effect of famotidine, could be reversed with bicucullin methiodide (specific GABA_A).¹⁹ It seems the plant extract, which increased GABA levels in the brain, protected the rats against the cold restraint ulceration. It is known that GABA and its agonists inhibit the central cholinergic action by affecting the turnover rate of acetylcholine in the rat brain.²⁰

Antitumor Properties: A crude extract and purified fractions of C. asiatica were tested on different tumor cell line models. Both the crude extract and purified fractions showed cytotoxicity against Erlich ascites and Dalton's lymphoma ascites tumor cells in a concentration-dependent manner. However, no cytotoxic effects were detected against normal cell lines. The oral administration of the extracts (crude or purified) retarded the development of solid and ascites tumors in mice.²¹

Antiviral/Antimycotic Activities: C. asiatica in combination with other Thai medicinal plants was investigated against herpes simplex virus type 1 and types 2 (HSV-1 and HSV-2). Vero cells, originating from an African green monkey kidney, were cultivated in growth medium and infected by HSV-1 and HSV-2. The plague inhibition assay was used to detect antiviral activities of the extracts.

C. asiatica extract showed inhibitory effect on plague formation and also reduced the yield of HSV-1 and HSV-2.²² Another study, using human embryonal muscle skin monolayer culture, tested 500 herbal extracts against HSV-2 infection, and sorted out C. asiatica as "highly effective" in controlling virus infection.²³

Antimycotic activity of C. asiatica was tested among 18 medicinal plants against Microsporum gypseum, Chrysosporum tropicum and Trichophyton terrestre. C. asiatica extracts very strongly inhibited the micellar growth of T. terrestre (61.7%), but it was less effective against M. gypseum (38.9%) and C. tropicum (14.9%).²⁴

Dosage

A typical daily dose is about 600 mg of dried leaves or infusion. The single-dose capsules, which may be taken three times daily, range from 300 mg to 680 mg. A 10-mg concentrated extract, also available in capsules, may be taken 3–6 times daily. Other brands and doses include Madecassol tablets 10 mg 3–6 times daily, Tincture 1–2 mL, and Emdecassol ointment twice daily.²

Precautions and Safety

Gotu kola has no known toxicity in recommended doses. The fresh plant may have a low potential for skin irritation; contact dermatitis has been reported on a few occasions using topical preparations.²⁵ Subcutaneous injections can trigger allergic reactions, cause pain at the injection site, or cause discoloration. Side effects occur less often when using intramuscular injections. Orally consuming an excessive amount of Gotu kola (i.e., overdose) can cause headaches and transient unconsciousness. Also, chronic treatment may prevent women from becoming pregnant.⁵ During prolonged treatment, especially with higher doses, the metabolism of asiaticoside to asiatic acid slows down proportionally to the plasma asiatic acid content. This pharmacokinetic phenomena should be considered for effective and safe treatment.²⁶

The growing number of herbal preparations on the market, including Gotu kola, raised the possibility of complications related to improper use of these products, or the lack of medical supervision. Several of the recent cases reported to The Special Nutritionals Adverse Event Monitoring System (SN/AEMS) indicate the importance of providing patient counseling on the use of herbal preparations.

Issue date: April 2001

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References

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