Introduction

Gotu kola is a creeping, low-growing (4-18 inches), perennial herb bearing fan-shaped, tasteless, odorless green leaves on thin stems and small white to purplish-pink flowers.^1-3 It commonly grows in damp, swampy areas of India, Sri Lanka, Madagascar, South Africa, and Central and South America,^1,2 and is widespread throughout tropical and subtropical Asian countries including Bhutan, China, Indonesia, Laos, Malaysia, Myanmar, Nepal, Pakistan, Thailand, and Vietnam.⁴ Most commercial material originates from India, but the finest quality is thought to come from Madagascar.² In Europe and North America, the plant part most often used for medicinal purposes consists of the dried aerial parts collected during the flowering period.² The dried whole plant (root, stems, leaves, and fruits) is used in the traditional Chinese and Indian Ayurvedic systems of medicine.^5,6

Gotu kola should not be confused with cola (Cola nitida, Sterculiaceae), aka kolanut, the seeds of which contain caffeine and are used in cola beverages.¹ Gotu kola contains no caffeine and is not a stimulant.^1,3 It should also be noted that in India, gotu kola is commonly adulterated or substituted with bacopa (Bacopa monnieri, Scrophulariaceae). Both are sold commonly in Indian markets under the same vernacular name Brahmi. Although official Ayurvedic texts are clear that Brahmi is the Sanskrit name for bacopa (whole plant) while Mandukaparni is the Sanskrit name for gotu kola (whole plant), Mandukaparni is also the regional name used for bacopa in the Hindi and Kanada languages, respectively, and both plant materials are named Brahmi in the Urdu language, among other vernacular confusions. However, bacopa can be recognized easily by both morphological characteristics and chemical assay.²

History and Cultural Significance

Centella asiatica (syn. Hydrocotyle asiatica) has over 60 common names in addition to those already mentioned; these include pennywort, Indian or water pennywort, marsh penny, ji xue cao, and talepetrako.^1,2 Gotu kola, in the the Sri Lankan Singhalese language, means cup-shaped leaf.⁴ Sri Lankans, noting that elephants, renowned for their longevity, eat the plant, began eating a few leaves a day in hopes of increasing their lifespan.^1,7 Gotu kola’s historical use is mentioned in the Chinese Shennong Herbal (circa 1st-2nd century CE). It has been called one of the “miracle elixirs of life” because a Chinese herbalist named Li Ching-Yun, who some believe lived to the age of 197 (but not the 256 or 265 years frequently cited), reportedly used gotu kola regularly.⁸

Gotu kola has been used as an aphrodisiac and to treat a variety of illnesses including abscesses, asthma, diarrhea, epilepsy, fever, hepatitis, high blood pressure, mental fatigue, stomach ulcers, and syphilis.^1-3 It was incorporated into the Indian Pharmacopoeia in the 19th century and accepted by the French as a drug in the 1880s.⁷

Today, gotu kola is most commonly utilized for a variety of conditions: the treatment of chronic venous insufficiency (CVI, a condition where the leg veins and their valves do not work effectively, impeding blood flow to the heart), burn wounds, stress-related duodenal ulcers, as a stomachic to tone the stomach and improve its function, and for skin conditions such as scleroderma (hardening of the skin and connective tissue), psoriatic arthritis (inflamed scaly skin with swollen, painful joints), and scabies (a parasitic infection caused by a mite).^1-3,9 Gotu kola is available as a dried herb or extract, in teas, ointments, tinctures, capsules, tablets, and in cosmetic preparations.³

In Ayurvedic medicine, gotu kola is best known as a mental rejuvenator, or medhya rasayana, a tonic used to reduce mental fatigue and improve mental clarity.¹⁰ It is also used for treating various types of skin conditions and internal and external ulcers, as well as for improving blood circulation and reducing edema. The specific therapeutic uses listed in the Ayurvedic Pharmacopoeia of India include the treatment of inflammation, tastelessness, fever, cough, itching, skin diseases, excessive urination, dyspnea (difficult breathing)/asthma, and anemia.¹¹ An important Ayurvedic formulation containing gotu kola is Brahma Rasayana, a complex mixture of herbs and fruits in a paste form, taken with warm milk as a cerebral tonic for mental exhaustion, nervous weakness, insomnia, and memory loss.

In traditional Chinese medicine (TCM), dried gotu kola whole plant, known as ji xue cao (at dosage of 15-30 g), or fresh plant (at dosage of 30-60 g) is indicated for treating jaundice, heat-stroke with diarrhea, urolithiasis (stones forming in the kidney, bladder, and/ or urethra), hematuria (blood in urine), carbuncles and boils, and traumatic injuries.⁵

Gotu kola is permitted by regulation in the United States for use in dietary supplements, cosmetics, and homeopathic preparations. In Canada, gotu kola is found as a component in licensed Natural Health Products with the approved claim statement, “Traditionally used in Ayurvedic medicine to relieve lack or loss of the appetite for food and to relieve cough.’’¹² In the United Kingdom, gotu kola is a General Sale List medicine for external use only.¹³ In November 2010, the European Medicines Agency (EMA) published a public statement that it is not possible to propose a Community Herbal Monograph for C. asiatica preparations at this time for 2 reasons: (1) Although the medicinal use of titrated extract of C. asiatica (TECA) has been established for at least 30 years in Europe, EMA has decided that TECA (commercially known as Madecassol^® or Centellase^® or Blastoestimulina^®) cannot be classified as an herbal preparation; it is a highly purified extract, fractioned and enriched in triterpenic acid and triterpenic sugar ester fractions to reach about 40% asiaticoside and 60% triterpenic genins (asiatic acid and madecassic acid). The purification steps involve chemical treatments that remove the herbal matrix. (2) Although some data are available on other gotu kola preparations, the available data was deemed insufficient for the development of a labeling standards monograph at this time.¹⁴ There is, however, an official European Pharmacopoeia quality standards monograph for the dried, fragmented, aerial parts of C. asiatica, containing minimum 6.0% of total triterpenoid derivatives, expressed as asiaticoside.¹⁵ As of 2011, 4 new gotu kola dietary supplement quality standards monographs are proposed for inclusion in the United States Pharmacopeia 34th Revision: Centella Asiatica, Powdered Centella Asiatica, Powdered Centella Asiatica Extract, and Centella Asiatica Triterpenes.¹⁶

Modern Research

The main chemical components in gotu kola are the triterpenes asiatic acid and madecassic acid, and the triterpene ester glycosides derived from them, asiaticoside and madecassoside.¹⁰ The new USP monograph assay includes 6 triterpenes: madecassoside, asiaticoside B, asiaticoside, madecassic acid, terminolic acid, and asiatic acid.¹⁶ Additional components include brahmoside, brahminoside, and hydrocotyline.^2,17

The majority of recent clinical studies conducted on gotu kola have addressed its effects on CVI, microangiopathy (a condition, frequently experienced in diabetes, wherein the walls of the capillaries become thick and weak, leading to bleeding, leaking protein, and slowing blood flow), and anxiety. A number of studies were conducted in the 20th century suggesting gotu kola’s benefits in wound healing, but no current clinical studies on this aspect of its use are available.

CVI causes blood to pool in the legs (stasis) and can result in venous hypertension, edema (swelling) of the legs, aching or tiredness in the legs, ulcerations, and varicose veins. Many gotu kola-CVI studies have been conducted by a group of European investigators using total triterpenoid fraction of C. asiatica (TTFCA, sometimes specified as Centellase^® [Bayer S.p.A., Milano, Italy]) and, while there is enough evidence to suggest efficacy, these studies have been criticized as methodologically flawed, inconsistent in dosing, too short (1-12 months), and using nonclinical endpoints.⁷

One 2-month, single-blind British trial randomized 99 participants to receive either 60 mg (30 mg twice daily) TTFCA, 120 mg (60 mg twice daily) TTFCA, or placebo, while healthy subjects were given 60 mg TTFCA thrice daily.¹⁸ Significant improvement in symptoms (edema, pain, muscle cramps, tired/heavy legs) was seen in those taking the TTFCA, more so in the ones taking the higher dose.

In a 4-month study, 3 groups of patients with venous hypertension were given either 30 mg or 60 mg TTFCA thrice daily, or placebo.¹⁹ After 4 weeks, capillary filtration rate, ankle circumference, and ankle edema were significantly improved in the 2 patient groups taking TTFCA, with greater improvement in the higher dose group. There was no significant change in either the placebo group or the healthy subjects taking TTFCA.

Another trial assessed the effect of TTFCA on edema and microcirculation in 40 patients with CVI who were randomized to receive either 60 mg TTFCA twice daily or placebo for 6 weeks.²⁰ Significant improvement in veno-arteriolar response, increase in pO₂ (blood oxygen pressure), decrease in pCO₂ (blood carbon dioxide pressure), decrease in leg volume, and decrease in resting blood flow were experienced by the treatment group.

Forty patients with severe venous hypertension, ankle-swelling, and lipodermatosclerosis (brown, smooth, tight, and often painful scarring of skin just above the ankle, usually on the inside surface) were included in a study in which one group received 60 mg TTFCA twice daily for 8 weeks; the other received placebo.²¹ The TTFCA treatment group experienced significant improvement in signs and symptoms of venous hypertension.

In one placebo-controlled trial, 50 patients with diabetic microangiopathy were randomized to receive 60 mg TTFCA twice daily, placebo, or no treatment.²² After 6 months, significant improvement in microrcirculatory parameters and decrease in capillary permeability were observed.

Another study on TTFCA and diabetic angiopathy randomized 100 patients (50 with neuropathy and 50 without) to receive 60 mg TTFCA twice daily or placebo for 12 months.²³ The TTFCA groups (with and without placebo.

Another study evaluated TTFCA’s effect on microangiopathy alterations in edema in passengers travelling by plane for more than 3 hours; subjects were randomized to receive no treatment or 60 mg TTFCA thrice daily for 2 days before the flight, the day of the flight, and the day after the flight.²⁴ The rate of ankle-swelling and edema were significantly lower in the TTFCA group.

One 2010 study investigated the effects of a 70% hydro-ethanolic extract of C. asiatica (JB Roy State Ayurvedic Medical College and Hospital, Kolkata, India) on generalized anxiety disorder in 33 participants.²⁵ Participants were given a 500 mg capsule twice daily after meals for 60 days. Results indicated that taking gotu kola significantly attenuated stress anxiety/depression-related disorders. Baseline score on anxiety index decreased to 13.1% in 30 days and 26% in 60 days and self-perceived stress improved 12.5% in 30 days and 23.2% within 60 days.

A double-blind, placebo-controlled study in 2000 evaluated the anxiolytic activity in gotu kola in healthy subjects.²⁶ Participants (n=40) were randomly assigned to receive either a singe 12 g orally administered dose of gotu kola (encapsulated crude powder, Nature’s Way, Canada) or placebo. Results showed that, compared to placebo, gotu kola significantly weakened the acoustic startle response 30 and 60 minutes after treatment but had no significant effect on self-rated mood, heart rate, or blood pressure.

At least 1 study has been done on C. asiatica and its effect on cognition and mood in healthy elderly volunteers.²⁷ Various doses of either 250, 500, or 750 mg of plant extract (Center for Research and Development of Herbal Health Product, Faculty of Pharmaceutical Sciences, Khon Kaen University, Thailand) were given daily to 28 participants for 2 months. Cognitive performance and mood were assessed after single treatment and at 1 and 2 months after treatment. Results suggest that gotu kola may lessen the age-related decline in cognition and mood in healthy elderly people.

Gotu kola has also been studied in combination with other herbs and conventional medications used both internally and topically for effectiveness in treating CVI,²⁸ atopic dermatitis,²⁹ photo-aged skin,³⁰ oral and topical phlebotonics for venous insufficiency,³¹ lymphdraining action in the treatment of ulcers of the lower limbs caused by slow-moving blood,³² for supportive periodontal therapy,^33,34 and on improving the appearance of striae rubra (red stretch marks).³⁵

Future Outlook

Total retail sales of gotu kola dietary supplements in the natural and health foods channel in the US totaled $530,686 in 2010, up 4.8% from the previous year.³⁶

There are very little recent data on the sustainability and marketability of gotu kola. In 2000, 1 source opined that most of the gotu kola on the US market was of poor quality, and that it was commonly harvested from ditches in India that were contaminated with heavy metals, pollutants, and other harmful chemicals.³⁷ In 2008, C. asiatica was reported to be one of the most important plants in the Indian medicinal plant trade, and that the plant had largely been depleted in the wild due to overharvesting and limited cultivation attempts.³⁸ Another 2008 report listed C. asiatica as one of 46 medicinal plant species in high trade in India sourced mainly from wastelands. It is reportedly found growing wild in abundance in wastelands including farm bunds (liquid-storage tanks), fallow lands, roadsides, and shrubberies. For this reason, it may not require immediate wild-resource management focus but could possibly benefit from being brought into cultivation in order to conform to quality standards.³⁹ In India, the commercial supply is now obtained from both cultivation and wild collection.⁴⁰ In China, it is wild collected for use in TCM preparations. Tissue culture techniques developed in a 2010 study may be useful for propagation of gotu kola and for helping to conserve the germplasm of the species.⁴⁰

In Madagascar, where gotu kola was considered one of the top 10 Malagasy medicinal plants, a 2004 report stated that quality standards had been identified and there was no threat to gotu kola nor to its habitats.⁴¹ It suggested that there was no need for management of gotu kola but that quality could be improved at the collection level, and information sheets regarding potential revenue stream were made available to women who collected the herb.

—Gayle Engels and Josef Brinckman

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