Centella asiatica (PROSEA)

Plant Resources of South-East Asia
Introduction

1, plant habit; 2, leaf; 3, stem base with young leaf, flowers and fruits; 4, inflorescence; 5, flower; 6, fruit (Iskak Syamsudin)

Centella asiatica (L.) Urb.

Protologue: Mart., Fl. bras. 11, 1: 287, pl. 78, fig. 1 (1879).

Family: Umbelliferae

Chromosome number: 2n= 18

Synonyms

Hydrocotyle asiatica L. (1753).

Vernacular names

Asiatic pennywort, Indian pennywort, gotu-cola (En).
Hydrocotyle asiatique (Fr).
Brunei: pegaga
Indonesia: daun kaki kuda, pegagan (general), antanan gede (Sundanese)
Malaysia: pegaga (general)
Philippines: takip-kohol, tapingan-daga (Tagalog), hahang-halo (Bisaya).
Singapore: pegaga.
Burma (Myanmar): min-kuabin
Cambodia: trachiek kranh
Laos: phak nok
Thailand: bua bok (central), pa-na-e khaa-doh (Karen, Mae Hong Son), phak waen (peninsular)
Vietnam: rau má, tích tuyết thảo.

Origin and geographic distribution

Centella comprises approximately 40 species with an amazing diversity in South Africa, where all species are confined except C. asiatica which has a pantropical distribution including South-East Asia and extending into some subtropical regions.

Uses

Asiatic pennywort has been used in southern Asia, India and China since prehistoric times for a wide range of complaints. In China, it has been known for many centuries as a medicinal plant with tonic and cooling properties, and (together with Hydrocotyle spp.) is known in pharmacology as "Folia Hydrocotyles".

The most important use of the whole plant is in skin-related diseases. Fresh leaves, fresh juice, a decoction or an extract are applied, depending on the complaints. Several over-the-counter preparations recommended for skin care are available, containing various extracts of the plant or one of its constituents asiatocoside. Extracts are applied topically in the adjunct treatment of surgical wounds and minor burns. The extract is used effectively in the treatment of keloids, leg ulcers, phlebitis, slow-healing wounds, scleroderma, lupus, leprosy, surgical lesions, striae distensae, cellulitis and aphthae. Purified extracts are known to accelerate cicatrizing and skin grafting.

Orally, the extract is indicated to relieve the symptoms of venous and lymphatic vessel insufficiency, and used to treat atonic wounds and for hypertrophic healing. The direct application of Asiatic pennywort as a drug is only rarely prescribed in Western medicine. More frequently, standardized extracts are utilized; these are applied orally, intramuscularly or subcutaneously. Asiatic pennywort has a considerable reputation for treating epilepsy. In Ayurvedic medicine in India, it is one of the ingredients of a non-alcoholic anti-epileptic syrup which showed significant anti-epileptic activity in tests with rats. It is also used in India and Thailand as a tonic and to treat dysentery. In Sri Lanka, an extract is used in traditional medicine as a galactagogue. Dry leaves are one of the ingredients of pills taken in Vietnam against senility, and are also used successfully in a complex preparation against acute infective hepatitis.

Asiatic pennywort is a relished vegetable in many South-East Asian countries (with the exception of the Philippines) and also in Sri Lanka. The slightly bitter leaves are eaten raw or cooked. In Thailand, Vietnam, Cambodia and Laos a softdrink is made from the juice of the leaves; the juice is diluted with water and some sugar is added. The popularity of Asiatic pennywort as a vegetable and soft drink is certainly related to its medicinal properties.

Production and international trade

The reported quantities of dried plants used by traditional drug manufacturers in Indonesia in the period 1991 to 1994 vary between 19-125 t/year. Most of Asiatic pennywort for commercial medicinal preparations comes from Madagascar. From 1979 to 1988, 26-96 t/year was exported from this country to all parts of the world for pharmaceutical use.

Fresh Asiatic pennywort is a common product on vegetable markets in South-East Asia. Usually plants are gathered from the wild, but it is cultivated commercially in Sri Lanka. No statistics are available. In Thailand a locally produced soft drink made from Asiatic pennywort is sold canned in supermarkets.

Properties

Several triterpenoid compounds have been isolated from Asiatic pennywort, the most important ones being asiaticoside, madecassoside, asiatic acid and madecassic acid. These are considered the pharmacologically active principles. In ethanolic extracts compounds such as β-sitosterol and stigmasterol have been demonstrated.

Several animal tests have confirmed that extracts have a wound-healing effect, and this activity has also been reported from clinical studies with humans. Patients with burns, cellulitis, leprotic infections and skin ulcers have been treated successfully in controlled studies. Asiatic acid, madecassic acid and asiaticoside have been tested separately and in combination on skin human fibroblast collagen I synthesis in vitro. The mixture as well as each individual component stimulated collagen I synthesis to a similar extent. Collagen I is involved in wound healing. A mixture of brahmoside and brahminoside exhibits antispasmodic, antipyretic, central nervous system-depressant and hypotensive activity.

Asiatic pennywort has shown promising narcotic analgesic activity mediated through opiodergic receptors. The ethanolic extract exhibited anti-stress activity and activity against stress-induced gastric ulcer formation in rats, comparable to that of diazepam. In a clinical test in Italy, patients with chronic venous insufficiency of various etiology were treated with Asiatic pennywort at a dose of 60 mg/day during 4 months. For most patients the drug was effective against the subjective symptoms, but did not show significant changes in conjunctival capillaroscopy. In a multicentre, double-blind placebo-controlled study in France with patients suffering from venous insufficiency of the lower limbs, a significant difference was found in favour of a titrated extract of Asiatic pennywort for the symptoms of heaviness in the lower limbs and oedema. The venous distensibility was improved by the extract. The triterpene fraction of Asiatic pennywort has an effect on the metabolism in the connective tissue of the vascular wall and on the microcirculation. Treatment with the triterpene fraction for 3 weeks caused a significant reduction in the number of circulating endothelial cells in patients with post-phlebitic syndrome.

An aqueous extract of Asiatic pennywort showed activity against the herpes simplex II virus. The recovery of guinea-pigs with experimentally induced tuberculosis was hastened by treatment with asiaticoside. This compound promotes healing through bacteriostatic activity and stimulation of the reticuloendothelium.

The anti-tumour effect of the crude extract of Asiatic pennywort and of partially purified fractions has been studied by in vitro short and long term chemosensitivity and by in vivo tumour model test systems. The proliferation of transformed cell lines was inhibited more by the partially purified fractions than by the crude extract. The 50% effective doses on 3-hour exposure to the fractions were 17 μg/ml for Ehrlich ascites tumour cells and 22 μg/ml for Dalton's lymphoma ascites tumour cells. Hardly any toxic effects were detected in normal human lymphocytes. At a concentration of 8 μg/ml the partially purified fractions also significantly suppressed the multiplication of mouse lung fibroblast cells. Oral administration of the extracts retarded the development of solid and ascites tumours and increased the lifespan of these tumour-bearing mice.

The sensitizing capacity of the raw extract and its triterpenic constituents asiaticoside, asiatic acid, madecassoside and madecassic acid has been studied in guinea-pigs. All were found to be very weak sensitizers; although applied frequently to damaged skin, the risk of acquiring contact sensitivity is low. The toxic dose of asiaticoside by intramuscular application to mice and rabbits is reported to be 40-50 mg/kg body weight. In oral applications, 1 g of asiaticoside per kg body weight has not proved toxic in rats. Asiatic pennywort is toxic in large overdose or as a result of long-term application. It can produce narcotic effects, headache, vertigo, and, occasionally in sensitive individuals, it may even lead to coma. Contra-indications include patients with cardiovascular disorders and internal bleeding. Besides the above activities, anti-amoebic and immunostimulant activity are also reported. Asiaticoside is related to chemical compounds with known oncogenic activity and it has been found to exhibit slight tumour-producing properties in experimental animals, but possible carcinogenic effects have not yet been investigated thoroughly. Reduction of fertility in female mice has also been reported for asiaticoside.

In the essential oil isolated by steam distillation from the aerial parts of Malaysian plants 41 compounds have been identified, with the sesquiterpenoids (80%) as the major category and β-caryophyllene (27%), α-humulene (34%) and germacrene-D (10%) as the most abundant. The major components in the essential oil from plants collected in Sri Lanka were α-copaene (14%), β-caryophyllene (12%), trans-β-farnesene (5%) and α-humulene (9%).

Per 100 g edible portion fresh leaves contain: water 88 g, protein 2 g, fat 0.2 g, carbohydrates 7 g, fibre 1.6 g, Ca 170 mg, P 32 mg, Fe 6 mg, provitamin A 4.5 mg and vitamin C 49 mg.

Adulterations and substitutes

Asiatic acid and asiaticoside have also been demonstrated in the bark of Schefflera heptaphylla (L.) Frodin (syn. S. octophylla (Lour.) Harms), which is used in Vietnamese traditional medicine as a tonic and to treat rheumatism. Asiatic acid has also been found in ether extracts of the wood of Terminalia brassii Exell and T. complanata K. Schumann.

Description

A small perennial herb, creeping with long stolons (up to 2.5 m long), rooting at the nodes; young parts more or less puberulous.
Leaves in rosettes, simple, lamina orbicular-reniform, 1-7 cm in diameter, regularly crenate or crenate-dentate, palmately veined, subglabrous; petiole 1-40(-50) cm long, glabrous to puberulous, broadened at the base into a leaf-sheath; stipules absent.
Inflorescence an axillary simple umbel, (1-)3(-7)-flowered with middle flower sessile and lateral flowers with a short pedicel and with involucre of 2 ovate bracts, 0.5-5 cm long peduncled, 1-5 together; scale-like leaves at base of peduncles about 3 mm long.
Flowers bisexual, 5-merous; calyx obsolete; petals roundish to broadly obovate, 1-1.5 mm long, entire, greenish, pinkish or reddish; stamens alternate with the petals; disk 2-lobed, plane with elevated margin; ovary inferior, 2-celled, styles 2.
Fruit consisting of 2 one-seeded mericarps connected by a narrow junction, separating when mature, oblate-rounded, strongly laterally compressed, 3 mm × 3-4 mm, mericarps distinctly 7-9-ribbed, ribs connected by veins, pubescent when young but often glabrescent.
Seed laterally compressed.
Seedling with epigeal germination; hypocotyl 2-4 mm long, glabrous; cotyledons broadly ovate to elliptical, shallowly emarginate at apex, glabrous; epicotyl absent.

Growth and development

Asiatic pennywort grows and flowers year round. In the Philippines, it is reported to be one of the main pollen sources for honeybees.

Other botanical information

C. asiatica seems related to Hydrocotyle species, but there is morphological, anatomical, palynological and phytochemical evidence for retaining it in Centella. Morphologically, Hydrocotyle differs particularly in its 3-ribbed mericarps, its free stipules at the base of the petiole, and its peltate or reniform leaves, in the latter case with lobed margins.

In Sri Lanka, where Asiatic pennywort is cultivated as a vegetable, two cultivars are distinguished: a small creeping form, and an erect bushy form with large leaves and petioles. The latter cultivar is most popular.

Ecology

Asiatic pennywort occurs in sunny or slightly shaded, damp localities on fertile soils (preferring sandy loams with much organic matter), e.g. along stream banks, on or near paths, alongside walls and in damp, open grassland, from sea-level up to 2500 m altitude. It is an early colonizer of fallowed land in shifting cultivation sytems, but may occur also on recently disturbed habitats and even on undisturbed sites. It may carpet the ground completely, but in regions with a monsoon climate usually only during the rainy season.

Propagation and planting

Asiatic pennywort can be easily propagated vegetatively by runners which root on the nodes, although reproduction by seed is possible. It often regenerates from fragments of stems buried in the soil during hoeing.

Stem pieces with one node are planted directly in the field or first in a nursery. Shading is not necessary, but sufficient soil moisture is essential. In Sri Lanka, planting distance is 30 cm × 25 cm for the bush type cultivar and 15 cm × 15 cm for the creeping type cultivar. A planting distance of 50 cm × 60 cm has been reported from Indonesia and Malaysia. At planting, organic fertilizer is added at a rate of 1.5 kg/m². Runners can be planted directly in the field ploughed to 20 cm deep.

In vitro production of active compounds

Cell suspension cultures of Asiatic pennywort can be grown on a modified Murashige and Skoog medium supplemented with growth regulators, 30 g/l sucrose and 500 g/l casein hydrolysate. They can be subcultured at intervals of 14 days in flasks on a shaker at 24 °C and a 16-hour photoperiod.

Cell suspension cultures are used to convert the cytotoxic compound thiocolchicine, a hemisynthetic substrate obtained from natural colchicine (from seeds of Colchicum autumnale L.), to thiocolchicoside (3-O-glucosylthiocolchicine), a drug used as a myorelaxant and analgesic. The thiocolchicine can be administered to 7-day-old suspension cultures, and the glucosides are localized intracellularly. Thiocolchicoside accounts for 85% of the glucosides. The cultures have also shown the ability to oxidize papaverine to papaveraldine. There is no known in vitro production of the active compounds of Asiatic pennywort.

Husbandry

Cultivated Asiatic pennywort does not need much care. A planting can be maintained for 2-3 years if only leaves are harvested. Every 6 months it needs to be fertilized with 1.5 kg/m² of organic material. Sometimes small amounts of urea are given, to stimulate leaf growth.

Diseases and pests

Asiatic pennywort is relatively little affected by diseases and pests. Bacterial wilt caused by Pseudomonas solanacearum has been reported from Sri Lanka, and a leaf spot disease caused by Cochliobolus geniculatus has been reported from India.

Harvesting

If circumstances are favourable, the first harvest can be obtained 2-3 months after planting. Subsequent harvests are possible every 2 months if only leaves are to be harvested. However, creeping types are usually harvested as whole plants. For medicinal use, whole plants are generally harvested at any suitable time of the year.

Yield

Bushy types may reach 8 t/ha of fresh leaves for the first harvest, and 14 t/ha for each subsequent harvest. Yields of the creeping types are lower.

Handling after harvest

After harvesting, plants to be used for medicinal purposes are stripped of their roots, cleaned with water and air-dried. The dried material should be kept in tightly closed containers and stored under dry conditions. Fresh leaves harvested as a vegetable are tied together in small bundles and marketed soon, as they wilt rapidly.

Genetic resources and breeding

Considerable genetic variation may occur between natural populations, due to the wide distribution of Asiatic pennywort. However, there are no known germplasm collections.

In a study of the presence of asiaticoside in various Indian ecotypes it appeared that the asiaticoside content differed significantly among them, with the highest amount (about 0.11%) in ecotypes from subtemperate Himalaya. Selection of genotypes with high asiaticoside content should be considered for commercial exploitation for medicinal purposes. No breeding work is being done.

Prospects

The medicinal value of Asiatic pennywort has been acknowledged in both traditional and modern medicine. Recent studies have confirmed the efficiency of the plant and its extracts in the treatment of skin injuries and diseases. Moreover, asiaticoside is reported to have considerable medicinal value against leprosy. Therefore, it is remarkable that hardly any commercial plantings exist. As a vegetable, however, cultivation on a larger scale is successful in Sri Lanka. Research on cultivation practices and breeding for specific purposes is needed prior to large-scale production in South-East Asia for medicinal purposes. A suitable method has already been developed for fingerprint analysis and standardization of all Asiatic pennywort preparations.

Literature

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Authors

Djoko Hargono, Pudji Lastari, Yun Astuti & M.H. van den Bergh