Centella asiatica

Alternative Medicine Review, March, 2007

Description

Centella asiatica (also known as gotu kola and Hydrocotyle asiatica) is a perennial, herbaceous creeper with kidney-shaped leaves, found in India, Sri Lanka, Madagascar, South Africa, Australia, China, and Japan. Centella prefers to grow in shady, moist, or marshy areas. (1,2)

Active Constituents

Centella contains several active constituents, of which the most important are the triterpenoid saponins, including asiaticoside, centelloside, madecassoside, and asiatic acid. In addition, Centella contains other components, including volatile oils, flavonoids, tannins, phytosterols, amino acids, and sugars. (3)

Mechanisms of Action

Centella has several pharmacological actions, based primarily on in vivo experiments. After oral and topical administration in rats, increased cellular hyperplasia and collagen production were noted at the site of injury, measured by increased granulation tissue levels of DNA, protein, total collagen, and hexosamine. More rapid maturation and cross-linking of collagen were seen in animals treated with the herbal extract, as evidenced by elevated stability of acid-soluble collagen and increases in aldehyde content and tensile strength. Compared to control wounds, rats treated with gotu kola had a higher degree of epithelialization and a significantly more rapid rate of wound contraction. (4,5)

In addition to improving wound healing, Centella may also have an effect on connective tissue of varicosities. After receiving 30 mg total triterpenoid fraction of Centella asiatica (TTFCA) twice daily for three months, individuals with varicose veins had significantly reduced serum enzymes involved in mucopolysaccharide metabolism (beta-glucuronidase, beta-N-acetylglucosaminidase, and arylsulfatase) compared to baseline values (p<0.01). (6)

The capacity to regenerate axons is an important component of healing following nerve damage. Rats given Centella extract in their drinking water recovered more quickly after nerve damage than controls, with increased axonal regeneration and more rapid functional recovery. (7)

The fresh juice extract of gotu kola at 200 and 600 mg/kg twice per day has proven to be protective against aspirin- and ethanol-induced gastric ulcers, (8,9) with similar effects as the medication sucralfate. (8) Centella significantly induced gastric mucin secretion and mucosal cell glycoprotein production, markers of increased gastric mucosal defense factors. (8)

Pharmacokinetics

A pharmacokinetic study suggests the active ingredients in TTFCA are well absorbed in human volunteers. (10) After single oral administration of 30 and 60 mg of the extract, maximum plasma levels of asiatic acid were reached at 4.5 and 4.2 hours, respectively. Plasma half-lives were 2.2 hours in the 30-mg dose and 3.4 hours in the 60-mg dose, with no detectable levels of the saponin present 24 hours after single dosing. Seven-day treatment with the herb at the same dosing schedule resulted in higher peak plasma concentrations, longer half-lives, and greater area-under-the-curve values. (10)

Clinical Indications

Venous Insufficiency

In a double-blind study, 94 patients (86 men, 8 women; ages 20-80) with venous insufficiency of the lower extremities for an average of 14 years, were randomized to one of three treatment groups: a triterpenoid extract of Centella asiatica (TECA) at a daily dose of 60 or 120 mg or placebo for three months. Individuals who took gotu kola at either dose demonstrated significant clinical improvements in limb heaviness (p=0.033), edema (p=0.026), and global evaluation of efficacy (p= 0.05). Venous distension, measured by plethysmography, was significantly better in the active group at 40 mmHg (p=0.08), 50 mmHg (p=0.055) and 60 mmHg (p=0.09), compared to deteriorating placebo values. (11)

Venous Hypertensive Angiopathy

Forty patients (21 males, 19 females; mean age 48 years) with severe venous hypertension, ankle swelling, and lipodermatosclerosis, were randomized to receive TTFCA 60 mg twice daily or placebo for eight weeks; patients in the study did not wear compression stockings. After trial conclusion, patients taking the herbal extract experienced a significant decrease in skin flux and rate of ankle swelling compared to baseline values (p<0.05). In addition, patients in the active group reported rapid clinical improvement, reflected by a reduction in the analogue scale line score (e.g., symptoms of edema, pain, restless limbs, swelling, and change in skin condition/color) from 9.5 at baseline to 4.5 after eight weeks. (12) In another study using Laser doppler evaluation, subjects taking 60 mg TTFCA twice daily for six weeks demonstrated a 29-percent decrease in resting flux (p<0.05), 52-percent increase in venoarteriolar response (p<0.05), and 66-mL reduction in leg volume. Similarly, those utilizing the herbal extract demonstrated 7.2-percent increase in p[O.sub.2] and 9.6-percent reduction in pC[O.sub.2] (p<0.05). (13)

Airline Flight Microangiopathy

Physical consequences of long-distance flights range from simple swelling of the lower limbs to the formation of dangerous blood clots. Centella's effectiveness was evaluated in 66 flight passengers (33 men, 33 women; mean age 38) traveling in economy class for 3-12 hours. Subjects were randomized to receive 60 mg TTFCA three times per day or a placebo two days before, the day of, and two days after the flight. Results showed significant improvements in microcirculatory function (transcutaneous p[O.sub.2] and pC[O.sub.2], laser doppler flowmetry, venoarteriolar response, rate of ankle swelling, and edema) in those utilizing TTFCA (p<0.05), with edema and rate of ankle swelling approached normal values in those given TTFCA (p<0.025). (14)