Centella asiatica (L.) Urb.

Scientific Name

Centella asiatica (L.) Urb.

Synonyms

Centella glochidiata (Benth.) Drude, Centella hirtella Nannf., Centella tussilaginifolia (Baker) Domin, Centella ulugurensis (Engl.) Domin, Centella uniflora (Colenso) Nannf., Chondrocarpus asiaticus Nutt., Chondrocarpus triflorus Nutt., Glyceria asiatica Nutt., Glyceria triflora Nutt., Hydrocotyle asiatica L., Hydrocotyle biflora P. Vell., Hydrocotyle brasiliensis Scheidw. ex Otto & F. Dietr., Hydrocotyle brevipedata St. Lager & St.-Lag., Hydrocotyle ficarifolia Stokes, Hydrocotyle ficarioides Lam., Hydrocotyle inaequipes DC., Hydrocotyle lurida Hance, Hydrocotyle nummularioides A. Rich., Hydrocotyle reniformis Walter, Hydrocotyle repanda Pers., Hydrocotyle sylvicola E. Jacob Cordemoy, Hydrocotyle triflora Ruiz & Pav., Hydrocotyle tussilaginifolia Baker, Hydrocotyle uniflora Colenso [1]

Vernacular Name

MalaysiaPegaga [2]
EnglishAsiatic pennywort, Indian pennywort, gotu-gotu [2]
ChinaJi xui cao [3]
IndiaVallarai (Tamil); brahma manduki, brahmi (Hindi); brahmi (Punjabi); manduki, darduracchada (Sanskrit); manimuni (Assamese); jholkhuri, thalkuri, thankuni (Bengali); khodabrahmi, khadbhrammi (Gujrati); ondelaga, brahmi soppu (Kannada); kodangal (Malayalam); karivana (Marathi); saraswati aku, vauari (Telugu); brahmi (Urdu) [4]
IndonesiaDaun kaki kuda, pegagan (General); antanan gede (Sundanese) [2]
BruneiPegaga [2]
SingaporePegaga [2]
ThailandBua bok (Central); pa-na-e khaa-doh (Karen, Mae Hong Son); phak waen (Peninsular) [2]
LaosPhak nok [2]
MyanmarMin-kuabin [2]
PhilippinesTakip-ko-hol, tapingan-daga (Tagalog); hahang-halo (Bisaya) [2]
CambodiaTrachiek kranh [2]
VietnamRau m[as], t[is]ch tuy[ees]t th[ar]o [2]
FranceHydrocotyle asiatique [2].

Geographical Distributions

Centella asiatica is originated from Asian and East African regions such as India, Sri Lanka and Madagascar. It spreads out to many countries including Malaysia, Pakistan, China, Japan, East Africa, West Indies, South America and Australia. It is commonly found growing in wet areas near river banks and canals. Most species survive well in open areas while others need some shade. [5][6]

Botanical Description

C. asiatica is a member of the family. It is a small perennial herb, creeping with long stolons up to 2.5 m long. The rooting system is at the nodes. Its young parts are more or less hairy. [2]

The leaves are in rosettes form and simple. The lamina is orbicular-reniform, 1-7 cm in diametre, regularly crenate or crenate-dentate, palmately veined and slightly smooth. Petiole is 40(-50) cm long, hairless to hairy, broadened at the base into a leaf-sheath. Stipules are absent. [2]

The inflorescence is an axillary simple umbel, (1-)3(-7)-flowered with sessile middle flower and lateral flowers are with a short pedicel and an involucre that consists of 2 ovate bracts with 0.5-5 cm long peduncles. Flowers are 5-merous bisexual. Sepal is obsolete. Petals are roundish to broadly obovate 1-1.5 mm long, entire, greenish, pinkish or reddish. The petals are 2-lobed disk and plane with elevated margin, arranged alternate with the stamens. The ovary is inferior, 2-celled and 2 styles. [2]

The fruit consists of 2 one-seeded mericarps connected by a narrow junction, separate when mature, oblate-rounded, strongly laterally compressed, 3 mm x 3-4 mm. Its mericarps are distinctly 7-9-ribbed; ribs connected by veins and hairy when young but often becoming hairless. [2]

The seed is laterally compressed. [2]

The seedling is with epigeal germination with 2-4 mm long hypocotyls and they are smooth. The cotyledons are broadly egg-shaped to elliptical, shallowly emarginated at apex and hairless. The epicotyl is absent. [2]

Cultivation

C. asiatica occurs in sunny or slightly shaded, damp localities, on fertile soils (preferring sandy loams with much organic mater), 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 coloniser of fallowed land in shifting cultivation systems, 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, it is usually only during the rainy season. [2]

Soil Suitability and Climate Requirement

C. asiatica survives well on sandy loam to sandy clay. It also grows on other soil types as long as not too sandy or clayey. For commercial production, the soil has to be more friable for easy harvesting process. Good soil is friable, fertile with high organic matter and with good drainage. Generally, C. asiatica needs 2,000-3,000 mm of rain annually but not more than 100 mm per month. Dry period of more than two months is not suitable but irrigation is needed if planting is continued. Too much rain makes the crop susceptible to root rot. [5][6]

Field Preparation

Land Preparation

Good land preparation is very important for good crop growth. The area has to be ploughed once with a disk plough followed twice using a rotovator. [5][6]

Production of Planting Materials

C. asiatica or ‘pegaga’ is normally planted using mature vegetative materials consisting of stem, leaves and roots. Cultivar ‘pegaga nyonya’ can be planted using the splits consisting of 8-10 plantlets. It can be directly planted in the field. [5][6]

9fig1
 Figure 1: The plantlets can be used as planting materials by splitting the mature plants.

Field Planting

Planting bed has to be prepared before planting. It can be done manually or by using a rotovator. The planting bed is 1.5 m wide at the base and 1.0-1.2 m high at the topmost. The length depends on the requirement and the planting area. The plant spacing is 20 cm between rows and 20 cm between plants. These planting distances give population density of about 125,000 per hectare. Planting is done at the onset of rainy season. [5][6]

Field maintenance

Fertilisation

Organic and inorganic fertilisers are usually applied in C. asiatica cultivation. Chicken manure can be used as the source of organic fertiliser together with enriched organic fertiliser such as complehumus (NPKTe: 8-8-8-3). When using chicken manure alone, 8.5 t/ha is applied 4-5 days before planting as basal fertiliser followed by 3.5 t/ha applied one month after planting. When combination of chicken manure and enriched organic fertiliser is used, a rate of 1.5 t/ha of chicken manure and 5 t/ha enriched organic fertiliser is applied as basal fertiliser. This is followed by 1.5 t/ha enriched organic fertiliser applied one month after planting. [5][6]

Weed Control

It is recommended to spray pre-emergence weedicide to hinder the germination of weed seeds after C. asiatica is sown. Three to four times of manual weeding is required until the canopy covers the bed fully. Weeding is then no longer required. Mulching using plastic or rice straw/dried lalang at the early stage of growth helps to control weeds efficiently as well as saves energy and cost due to manual weeding. [5][6]

Water management

Sufficient water supply is needed for C. asiatica cultivation. C. asiatica is short-rooted plants where the roots are found near the soil surface. Irrigation is crucial during the first two weeks after planting. Watering is needed once in 2-3 days after two weeks of planting. A micro-sprinkler irrigation system is recommended for C. asiatica. [5][6]

9fig2
 Figure 2: Field planting of C. asiatica on mineral soil.

Pest and Disease Control

The most common diseases are bacterial wilt caused by Pseudomonas solanacearum and root rot by Sclerotia. This occurs when the environment is too damp. To control these diseases, the plant has to be pulled out and removed to avoid spreading to other plants. Insect pests that usually attack C. asiatica are leaf hopper and white fly. [5][6]

Harvesting

C. asiatica is harvested six times (main crop and five ratoon crops) within one year of planting. The main crop of cultivar ‘pegaga nyonya’ is harvested 80-90 days after field planting. Each ratoon crop is harvested every 50-60 days after the first harvest. The average fresh yield of cultivar ‘pegaga nyonya’ for both main harvest and ratoon crops is 20 t/ha. [5][6][7]

9fig3
 Figure 3: Harvesting of C. asiatica for fresh market.
9fig4
 Figure 4: Sorting and cleaning of C. asiatica.

Postharvest handling

Harvested C. asiatica should be cleaned by using running water. For fresh market, it is bundled at one kilogramme each. C. asiatica harvested for making herbal tea or for extraction of active ingredients, the plant materials are dried in a drier at temperature of 40oC. [5][6]

Estimated cost of production

The total input cost is RM5,300-RM35,500. High input cost is during the main crop but the cost reduces during ratoon crop. The high cost is due to the cost of planting materials of about RM22,800 for the main crop. No costs incurred in the ratoon crop. The labour cost is RM4,500-RM10,800. The average cost of production (for main and ratoon crop) is RM20,355. With the fresh yield averaging 20 t/ha at every harvest, the production is RM0.97/kg. The production cost was estimated based on the cost of current inputs during writing of this article. [5][6][7]

Chemical Constituent

Water extract of C. asiatica has been found to contain centellosides D-E, pectin and acidic arabinogalactan. [8][9][10]

The ethanol extract had triterpenes (e.g. 2α,3β,20,23-tetrahydroxyurs-28-oic acid, 2α,3β,23-trihydroxyurs-20-en-28-oic acid), triterpenoid glycosides (e.g. asiaticoside, asiaticosides A-F, madecassoside, scheffuroside B) and a saponin (e.g. 2α,3β,23-trihydroxyurs-20-en-28-oic acid-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl -(1→6)-O-β-D-glucopyranosyl ester). [11][12][13][14] The methanol extract had triterpenes and triterpenoids (e.g. ursolic acid lactone, ursolic acid, pomolic acid, 2α,3α-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, corosolic acid, asiaticoside, madecassoside, asiatic acid, 6β-hydroxyasiatic acid, 3-O-[a-L-arabinopyranosyl]-2α,3β,6β,23-a-tetrahydroxyurs-12-ene-28-oic acid), a phenolic (e.g. rosmarinic acid), a steroid (e.g. b-sitosterol 3-O-b-glucopyranoside) and others (e.g. 8-acetoxy-1,9-pentadecadiene-4,6-diyn-3-ol, centellin, asiaticin, centellicin) [15][16][17][18]. The methanol-water extract had phenolics (e.g. castilliferol, castillicetin, isochlorogenic acid) [19].

C. asiatica has also been reported to contain brahmic acid, 3β-6β-23-trihydroxyolean-12-en-28-oic acid, 3β-6β-23-trihydroxyurs-12-en-28-oic acid, α-terpinene, thymol methyl ether, sceffoleoside A, bayogenin, centellasaponins B-D, centellose, D-gulonic acid, meso-inositol, docosyl ferulates) [20][21][22][23][24]. In addition, its cell cultures had irbic acid, chlorogenic acid and triferulic acid [25].

Active principles of C. asiatica have been reported as pentacyclic tirterpenes, (e.g. asiatic acid, asiaticoside, madecassic acid and madecassoside). [26]

Plant Part Used

Aerial parts, whole plant. [27]

Traditional Use

C. asiatica is traditionally used for albinism, anemia, asthma, bronchitis, cellulite, cholera, constipation, dermatitis, diarrhea, dizziness, dysentery, dysmenorrhea, dysuria, epistaxis, epilepsy, haematemesis, hemorrhoids, hepatitis, hypertension, jaundice, leucorrhoea, nephritis, nervous disorders, neuralgia, measles, rheumatism, smallpox, syphilis, toothache, urethritis and varices. It is also used as an antipyretic, anti-inflammatory and a “brain tonic” [28][29][30]. Poultices of C. asiatica have been used to treat contusions, closed fractures, sprains and furunculosis [30].

Preclinical Data

Pharmacology

Cytotoxic and antitumour activity

Methanol (80%) extract and acetone fraction of methanol (80%) extract of C. asiatica whole plant inhibited proliferation of Ehrlich ascites tumour cells (concentration of 50% cell death 62 and 17 μg/mL, respectively) and Dalton’s lymphoma ascites tumour cells (75 and 22 μg/mL, respectively). The acetone fraction also suppressed multiplication of mouse lung fibroblast (L-929) cells at a concentration of 50% cell death of 8 μg/mL. Both the crude extract and the acetone fraction of C. asiatica significantly reduced the development of murine solid tumours when administered simultaneously with tumour transplantations or given 10 days prior to tumour transplantation. The latter finding suggested a mechanism which involves stimulation of the immune system. The crude methanol extract (1 mg/g body weight) also significantly (p < 0.001) reduced ascites tumour growth and increased the life span of Ehrlich ascites tumour bearing mice. The mechanism may involved inhibition of DNA synthesis. [31]

Methanol (80%) extract of C. asiatica whole plant exhibited concentration dependent cytotoxicity towards human breast cancer cell line MCF-7 by apoptosis with LD50 value of 66 mg. Asiatic acid (10 µM) was found to kill ~95% cells. [32]

Antigenotoxicity activity

The extract of C. asiatica also regulates the genotoxicity which will lead to the protection of human lymphocytes. [33]

Wound healing activity

Titrated extract of C. asiatica plant that constituted of asiatic acid, madecassic acid and asiaticoside (40 mg) injected to male Sprague-Dawley rats twice a week for 4 weeks had wound healing effect by stimulation of glycogen and glycosaminoglycan synthesis and fasten the new formation of connective tissue. [34]

A laboratory animal study reported that various formulations (ointment, cream, and gel) of an aqueous extract of gotu kola applied to open wounds in rats (applied topically 3 times daily for 24 days) with the result of increased cellular proliferation and collagen synthesis at the wound site, as shown by an increase in collagen content and tensile strength. It was found that the C. asiatica treated wounds epithelialized faster and the rate of wound contraction was higher when compared to the control wounds. Healing was more prominent with the gel product [35]. It is believed to have an effect on keratinization, which aids in thickening skin in areas of infection [36].

A formulation with C. asiatica plant extract induced proliferation of granulation tissue and increased tensile strength when applied locally on wounds in rats and decreased the area of skin necrosis caused by burns [37]. The plant also purportedly reduced scarring and stimulated skin growth by acting on the production of collagen fibres by fibroblasts and resulted in a decrease in the inflammatory reaction and myofibroblast production [38].

Asiaticoside which is one of the C. asiatica constituents has been reported to possess wound healing activity by increasing collagen formation and angiogenesis [39][40]. In a laboratory animal study, the effects of asiaticoside on antioxidant levels was examined, as antioxidants have been reported to play a role in the wound healing process. It was concluded that asiaticosides may enhance induction of antioxidants at an initial stage of wound healing, but continued application of the preparation seem not to increase the antioxidant levels in wound healing [41]. C. asiatica may assist in the maintenance of connective tissue. In the treatment of scleroderma, gotu kola C. asiatica may also assist in stabilizing connective tissue growth, reducing its formation [42].

Antigastric activity

Aqueous extract of C. asiatica (0.05, 0.25 and 0.50 g/kg) significantly inhibited ethanol-induced gastric lesions and decreased mucosal myeloperoxidase in a dose dependent manner when the extract was given before ethanol administration. These results suggest that C. asiatica protected the gastric mucosa by improving the integrity of the mucosal lining while reduction of myeloperoxidase and gastric lesions could be due to a decrease in the recruitment of neutrophils by C. asiatica or to its free radical scavenging activity [43].

The water extract of C. asiatica whole plant (0.10 and 0.25 g/kg) and asiaticoside (5 and 10 mg/kg) given orally for 7 days to male Sprague-Dawley rats with acetic acid induced gastric ulcers were found to decrease the ulcer sizes (p< 0.01). This was due to the reduction of myeloperoxidase activity (p< 0.01) and promotion of epithelial cell proliferation (p<0.01) by upregulated expression of basic fibroblast growth factor in the ulcer tissues [44]. The extract and asiaticoside also inhibited inducible nitric oxide synthase activity (p< 0.01) and protein expression at the ulcer tissues [45].

Radioprotective activity

The aqueous extract of C. asiatica whole plant (100 mg/kg body weight) given orally to 6-8 weeks old Swiss Albino mice irradiated with Co-60 gamma radiation was reported to significantly increase survival time. [46]

Antimicrobial activity

Antibacterial

Essential oil of C. asiatica showed a broad spectrum of antibacterial activities against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Shigella sonnei) organisms. Activity against Gram-positive bacteria was greater than against Gram-negatives. Germacrene compounds in the essential oil are known to be strong antimicrobial and antitumour agents. [47]

Antiviral

In vitro study of aqueous extract of C. asiatica showed intracellular activities against Herpes Simplex Viruses, containing both anti-HSV-1 and –2 activities. [48]

Antioxidant activity

Ethanol extracts of all plant parts (leaves, petioles and roots) of C. asiatica showed significant antioxidant activity (p<0.05) in the concentration range of 1000-3000 ppm. [49]

Methanol extract of C. asiatica whole plant (50 mg/kg/day) administered orally to 2-month old lymphoma-bearing male Swiss mice for 14 days significantly increased the antioxidant enzymes of superoxide dismutase, catalase and glutathione peroxidase, as well as the glutathione and ascorbic acid antioxidants in the liver and kidney. [50]

C. asiatica extract (0.3%) and powder (5%) reduced oxidative stress when given to H2O2-exposed rats for 25 weeks. There was a reduction in erythrocyte malondialdehyde levels as well as a decrease in the superoxide dismutase activity of these rats given C. asiatica although the catalase activities were higher than in the H2O2-fed rats. [51]

Aqueous extract of C. asiatica was shown to be able to improve oxidative stress by being a neuroprotective as well as regulate endogenously. [52]

Neuropharmacology activity

Several laboratory studies have found that C. asiatica extracts help decrease cognitive impairment in rat models of Alzheimer’s disease (AD) and stimulating property on neuronal dendrites of hippocampal region. The mechanism of neuroprotection includes enhancement of the phosphorylation of cyclic AMP response element binding protein (CREB) and inhibition of ERK/RSK signaling pathway. [53]

Aqueous extract of C. asiatica whole plant (300 mg/kg) given to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in aged Sprague-Dawley rats for 21 days protected the brain against neurodegenerative disorders with reference to examination of the oxidative biomarker levels in corpus striatum and hippocampus homogenate. [54]

Hydroalcoholic extract of C. asiatica leaves possesses potential anticonvulsant, antioxidant and central nervous system (CNS) depressant actions. The extract (100 mg/kg) showed 50% protection while a higher dose (200 mg/kg) completely protected against pentylenetetrazol-induced convulsions in rats. The extract also protected against convulsions induced by an increase in current electroshock and by strychnine. Spontaneous motor activity was reduced while diazepam withdrawal-induced autonomic hyperactivity was potentiated as was the pentobarbitone sleeping time in mice. The extract (100-150 mg/kg) significantly reduced the normal body temperature of mice, while in brain homogenates it (1.3-40 mg/mL) reduced the formation of lipid peroxidation products. [55]

Aqueous extract of C. asiatica (100-300 mg/kg) was able to prevent cognitive deficits in intracerebroventricular streptozotocin-induced cognitive impairment in rats after 14 and 21 days indicating improved acquisition and retention of memory. These doses of C. asiatica did not affect spontaneous locomotor activity in these rats thus excluding the possibility that the CNS depressant/stimulant activity of the herb had contributed to the changes in the passive avoidance and elevated plus maze tests. After 21 days of treatment in the same groups of rats, the extract (200 & 300 mg/kg) significantly reduced brain malondialdehyde levels and increased brain glutathione levels without affecting brain superoxide dismutase activity while brain catalase levels were increased by the highest dose of the extract (300 mg/kg). [56]

The asiaticoside constituent of C. asiatica showed phospholipase A enzymes inhibition in the brain. [57]

Anxiolytic activity

The triterpine contents in C. asiatica extract showed anxiolytic activity and there are possibility of synergistic effect between terpene and asiaticoside. [58]

Toxicity

Aqueous extract of C. asiatica (5 mg/plate) lack cytotoxicity and mutagenicity on Salmonella typhimurium TA98 or TA100 with or without S9 mixture [59]. Acetone fraction of C. asiatica extract did not induce cytotoxicity in normal human lymphocytes at a 50 µg/mL. Oral administration the crude extract and the acetone fraction of C. asiatica to normal and tumour bearing mice at maximal concentrations of 500 mg/mouse did not produce any toxic symptoms while the body weights of the mice were increased [31].

Acute toxicity

Oral single dose acute toxicity study of aqueous mixture of C. asiatica whole plant powder on female Sprague Dawley rats (aged between 8 and 12 weeks old) showed no toxic effects on the parameters observed, including behaviors, body weight, food and water intake. All rats were observed for 14 days prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality. LD50 value was determined as > 2000 mg/kg. [60]

Clinical Data

Clinical findings

Adjunctive periodontal treatment

A herbal medicament containing C. asiatica and Punica granatum extracts in the form of biodegradable chips for subgingival application elicited significant improvements of pocket depth and attachment level in adult periodontitis patients. [61]

Weigh lost

Slimming liposomes containing esculoside, C. asiatica extracts, caffeine and L-carnitine potentially could provide a slimming effect in human volunteers. The slimming liposomes induced a dramatic increase in cyclic adenosine monophosphate content in human adipocytes, with a subsequent rise in the nonesterified fatty acids content of the incubation medium in in vitro experiments. The slimming liposomes antagonized a2-adrenergic receptors which should subsequently lead to down-regulation of lipolysis. [62]

Antidiabetic activity

30 patients with diabetic microangiopathy treated for six months with a total triterpenic fraction of C. asiatica (60 mg twice daily) led to significant improvement in microcirculation, decreased capillary permeability and also protected against microcirculation deterioration in these patients. [63]

Cognition improvement

A small randomized, placebo-controlled, double-blind study in healthy volunteers found that C. asiatica extract can improve age-related cognitive decline and also plays a role in memory enhancing as well as improvement of mood in high dose administration manner. [64]

Stretch marks during pregnancy

C. asiatica preparations may also be helpful in decreasing the stretch marks (striae gravidarum) that many women develop during pregnancy. A placebo-controlled study of 100 pregnant women compared application of a cream containing a C. asiatica extract, vitamin E (alpha tocopherol), and collagen-elastin hydrolysates to placebo. Application of the compounded cream was associated with less women developing stretch marks than in placebo. [65]

Scar reduction

Application of preparations of C. asiatica kola topically may also be beneficial in decreasing the scarring seen during wound healing, appearing to be related to the stimulation of maturation of the scar by the production of type I collagen and the resulting decrease in the inflammatory reaction and myofibroblast production. [66]

Anxiolytic activity

In a double-blind placebo-controlled study, a single 12 g dose of C. asiatica (encapsulated crude powder herb) was administered to 20 healthy subjects and 20 controls given the placebo. Compared with the placebo-treated group, C. asiatica significantly attenuated the peak acoustic startle response amplitude at 30 and 60 minutes after treatment without having any significant effect on self-rated mood, heart rate or blood pressure. This early findings suggest that the herb may have anxiolytic activity in humans and the anxiolytic activity may in part be due to binding to cholecystokinin receptors and cholinergic enhancement. [67]

Hepatoprotective activity

Titrated extract of C. asiatica showed possible therapeutic activity in chronic hepatic disorders patients. It reportedly stimulates the formation of hyaluronidase and chondroitin sulfate, as well as exerting a balancing effect on the connective tissue. [68]

Antihypertensive activity

One of C. asiatica’s primary effects appears to be on connective tissues by strengthening weakened veins. [69]

C. asiatica has been reported to act on the connective tissues of the vascular wall, being effective in hypertensive microangiopathy and venous insufficiency and decreasing capillary filtration rate by improving microcirculatory parameters of patients with chronic venous hypertensive microangiopathy [70]. A double-blind, placebo-controlled study of the effects of an oral standardized C. asiatica product in 87 patients with chronic venous hypertensive microangiopathy was conducted. The C. asiatica product was given for 60 days (30 mg twice daily and 60 mg twice) versus placebo. Microcirculatory parameters were improved as compared to placebo and seemed to be dose dependent, with the higher dose improving symptoms more significantly [71].

Another study reported the beneficial effects of an oral standardized C. asiatica product (60 mg three times a day) in vascular permeability and microcirculation as assessed by laser Doppler flowmetry. The results showed a combined improvement of the microcirculation and capillary permeability in all patients (10 normal subjects, 22 patients with moderate, superficial venous hypertension, and 12 patients with postphlebitic limbs and severe venous hypertension). [72]

Another study in patients with severe venous hypertension due to deep venous disease reported that a standardized C. asiatica product was acutely effective in reducing capillary filtration and edema in individuals with venous hypertensive microangiopathy. [73]

Precautions

No documentation.

Side effects

Allergic contact dermatitis has been associated with several topical products containing C. asiatica extract [74][75][76]. It was reported present after topical administration of the herb or its constituent [77]. Asiaticoside, a major triterpenic acid in C. asiatica was thought to be allergenic [78].

C. asiatica raw extract and its triterpenic constitutents namely asiaticoside, asiatic acid and madecassic acid showed a weak sensitizing capacity when studied in guinea pigs. [79]

Pregnancy/Breast Feeding

No documentation.

Age limitation

No documentation.

Adverse reaction

Hepatotoxicity was seen with C. asiatica ingestion. [80]

Interaction & Depletion

No documentation.

Interaction with drug

No documentation

Interaction with other Herbs

No documentation

Contraindications

No documentation

Case Report

Three women aged 61, 52 and 49 years old developed jaundiced after taking C. asiatica for 30, 20 and 60 days, respectively. Their respective pathological diagnoses were granulomatous hepatitis with marked necrosis and apoptosis, chronic hepatitis with cirrhotic transformation and intense necroinflammatory activity, and granulomatous hepatitis. All patients improved with discontinuation of C. asiatica although damage recurred in the first patient who again took the herb for two weeks. The second woman reported a similar history a year before accompanied by elevated hepatic enzymes and a negative viral serology when she took the herb for six months. At that time, the jaundice disappeared one month after stopping the herb. The damage produced by C. asiatica was attributed to the triterpene active principles present in the herb which may have induced apoptosis and cell death through an alteration of cell membranes. An immune-mediated mechanism was postulated to underlie the damage as autoantibodies and granulomas were present. [80]

A 38-year old man developed eczematous response on his ears to a preparation which contained C. asiatica extract. He showed positive patch tests with GEIDC standard series and C. asiatica extract. [78]

A 18-year old woman presented with a pruritic eczematous eruption on an interdigital joint and face following the topical application of an ointment that contained C. asiatica extract. She showed positive patch tests to the C. asiatica ointment preparation (applied as is) and to a titrated extract of C. asiatica. [43]

A 42-year old woman with no atopic history developed severe dermatitis of the legs after application of a cream that contained C. asiatica extract. Patch testing with C. asiatica extract showed positive in this woman. [74]

Four women aged 33, 23, 26 and 18 years old developed contact dermatitis following the application of an ointment which contained C. asiatica extract for between 4 to several weeks. All four women showed positive patch tests with the ointment. [77]

Poisonous Management

No documentation.

Line Drawing

Figure 1: The line drawing of C. asiatica. [2]

References

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in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​