Phytochemical and pharmacological potential of Acanthus ilicifolius.

Acanthus ilicifolius (Acanthaceae) has received considerable attention due to its wide range of secondary metabolites and its traditional usage in Indian and Chinese system of medicine. This plant is reported to be a mangrove. Mangrove survives in the most hostile environment with fluctuating tidal and saline regime. Hence, these plants are considered to be rich sources of steroids, triterpenoids, saponins, flavonoids, alkaloids, and tannins. Present review article is an attempt to cover recent developments in phytochemical and pharmacological potential of drug. Traditionally, the plant has been used for dyspepsia, paralysis, asthsma, headache, rheumatism, and skin diseases. The plant is known as 'Krishnasaireyaka' or 'Karimkurunji', is one of the 9 plants equated to the drug 'Sahachara,' which is used in Ayurvedic medicine for rheumatic complaints. The plant has not been explored to its full potential. The review will be a good reference tool for investigators who wish to work on natural compounds with free radical scavenging activity to combat diseases associated with stress.

The drug consists of leaves of Acanthus ilicifolius Linn. (Acanthaceae). A gregarious shrub, commonly found with mangroves along the coastal regions of India. The common names of Acanthus ilicifolius are Beng. Harkucha kanta, Eng. Holy leaved acanthus, Hind. Harkukanta, Kan. Holechudi, Mal. Payinachulli, Mar. Marandi, Mandli, Tam. Attumulli, Kaludaimulli, Tel. Alasyakampa, Alchi. It is found commonly in the east and west coasts, also found in Meghalaya and the Andamans. Leaves are simple, oblong to elliptic, varying in size, smaller in flowering season, measuring 7.5 to 15 cm in length and 5 to 6 cm in width, pinnatified, apex truncate to acute, terminating in a sharp spine, surface glabrous, granular; venation reticulate, veins strong, conspicuous, especially on the lower side, lateral veins 3 to 5 on each side terminating in a sharp 3 to 10 mm long spine at the toothed margin, spines longer in flowering season; petiole short, 5 to 6 mm in length, slightly winged with two sharp spines at the base; color dark green when fresh, yellowish-brown on drying. Odor indistinct, taste bitter.[1-3]

Phytochemical Work

Different classes of chemical constituents have been isolated and characterized from Acanthus ilicifolius. Ethanolic/Methanolic/Chloroform/Hexane extracts obtained from different parts of the plant like root, leaves, aerial parts, stem, pods have been found to contain different chemical moieties: Alkaloids, glycosides, lignans, triterpenoid saponins, sterols, fatty acids, and coumaric acid derivatives [Table 1].

Table 1

Chemical compounds reported in Acanthus ilicifolius

Pharmacological Work

Anti-inflammatory activity

The methanolic extract of the plant was tested for analgesic activity in mice in dosage of 1 to 100 mg/kg i.p. The extract showed graded analgesic activity ranging from 42.8 to 85.7% in the tail clip method. The ED50 was 2.5 ± 1 mg/kg compared to 10.0 ± 3.1 mg/ kg of pethidine hydrochloride. Graded protective effect ranging from 31.1 to 70.7% was also seen against hydrochloric acid-induced writhing in mice. The ED50 of the extract administered was 13.0 ± 1.5 mg/kg compared to 240 ± 34.1 mg/kg of sodium salicylate. The extract (5 mg/kg i.p.) exhibited significant anti-inflammatory activity against carrageenan-induced edema in rats. In acute toxicity test, the extract did not show any mortality in mice in doses up to 1 g/ kg i.p.[20]

The methanolic fraction of A. ilicifolius leaf extract produced significant inhibition of rat paw edema when administered both prior to and after carrageenan administration, in a manner similar to BW755C, a synthetic cyclooxygenase and lipooxygenase inhibitor. The extract decreased protein exudation and leukocyte migration in the peritoneal fluid, thereby indicating its effectiveness towards inhibiting peritoneal inflammation. It also produced significant inhibition of cyclooxygenase 1 and 2 and lipooxygenase activity. Preincubation of the extract inhibited the production of proinflammatory cytokines in lipopolysaccharide-stimulated peripheral blood mononuclear cells.[21]

Anti-leishmanial activity

2-Benzoxazolinone (BOA) isolated from the leaves revealed in vitro anti-leishmanial activity against Leishmania donovani. No mortality was observed in mice when BOA was administered (i.p.) in the doses ranging from 0.25-1 g/kg. The LC50 value for BOA was found to be 40 μg/ml and compared well with pentamidine.[22]

Osteoblastic activity

A coumaric acid derivative called acancifoliuside was isolated from the methanolic extract of the leaves. Its effects were tested on the functions of osteoblastic MC3T3-E1 cells. It increased the growth and differentiation of osteoblasts significantly, indicating that A. ilicifolius leaves may help to prevent osteoporosis.[18]

Hepatoprotective activity

The oral administration of the alcoholic extract (250 and 500 mg/kg) significantly reduced CCl4-induced hepatotoxicity in rats as judged from the serum and tissue activity of marker enzymes. The results were comparable with those obtained with curcumin 100 mg/kg,p.o.[23]

Anti-cancer activity

To investigate the chemopreventive efficacy of A. ilicifolius in a transplantable Ehrlich ascites carcinoma (EAC) bearing murine model, male Swiss albino mice were divided into 4 groups: Group A was untreated normal control; Group B was the Ehrlich ascites carcinoma control mice group that received serial, intraperitoneal inoculations of rapidly proliferating 2 × 10(5) viable Ehrlich ascites carcinoma cells in 0.2 ml of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract of A. ilicifolius at a dose of 2.5 mg/kg body weight by single ip injections, once-daily for 10, 20, and 30 consecutive days following tumor inoculation (aq. leaf extract of A. ilicifolius); and Group D was the Ehrlich ascites carcinoma + aq. leaf extract of A. ilicifolius treatment group.[24]

Alcoholic extract of A. ilicifolius (250, 500 mg/kg body weight) was found to be effective against tumor progression and carcinogen-induced skin papilloma formation in mice. The extract was found to be cytotoxic towards lung fibroblasts (L-929) cells in 72 h MTT assay, and the concentration required for 50% cell death was 18 μg/ml. Oral administration of the extract (500 mg/ kg body wt) reduced the tumor volume, and administration of the same concentration increased the life span by 75% in ascites tumor harboring animals. The extract also significantly delayed the onset of dimethylbenzanthrazene/croton oil-induced skin papilloma in mice in a dose-dependent manner.[25]

Screening of different extracts and fractions from the plant A. ilicifolius has been conducted using the in vitro comet assay for anti-cancer using Hela and KB cell lines. The air-dried whole plant was sequentially extracted by n-hexane, chloroform, and methanol. The extracts were fractionated with ethyl acetate, acetone, and water. All the extracts and fractions were tested for anti-cancer activity by comet assay. Ethyl acetate extract of the whole plant showed significant anti-cancer activity.[26]

Anti-ulcer activity

The anti-ulcer activity of methanolic extracts of A. ilicifolius leaves (MEAI) was investigated in pylorus ligation and ethanol-induced wistar models in wistar albino rats. In both models, common parameter determined was the ulcer index. MEAI at doses of 100, 20 mg/kg body weight produced significant inhibition of gastric lesions induced by pylorus ligation and ethanol-induced gastric ulcers. The extract showed significant reduction in the gastric volume, free acidity, and ulcer index as compared to control. This suggests leaf methanolic extracts were found to possess anti-ulcerogenic as well as ulcer healing properties, which might be due to anti-secretary activity.[27]

Anti-microbial activity

The anti-microbial activity of n-hexane, chloroform, and methanol extracts of leaves and roots of the plant A. ilicifolius were studied. Ampicillin and clotrimazole were used as standard anti-bacterial and anti-fungal agents, respectively. The result of the study revealed that the n-hexane and chloroform extract of the leaves exhibited strong inhibitory action against Bacillus subtilis, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus, and Aspergillus niger and moderate inhibitory action against Pseudomonas aeruginosa and Proteus vulgaris.[28]

The anti-microbial activity of ethanol, methanol, and aqueous extracts of leaves, stem, and root of A. ilicifolius were studied. These created an interest to test the possible anti-microbial activity of different part of this plant, which has not been reported. The cub-plate agar diffusion method was employed to assess the activity. 11 test microorganisms were used in this study. Microorganism were grown overnight at 37°C in the Mueller-Hinton broth at pH 7.4. The data obtained were subjected to ANOVA test.[29]

The anti-microbial activity of crude extract against bacterial and fungal pathogens showed the clear inhibition zone against Vibrio cholerae and Aspergillus niger, and aqueous extracts showed clear inhibition zone for Psuedomonas sp. and Candida albicans.[30]

The anti-microbial activity of alcoholic, butanolic, and chloroform extracts of leaves and roots of the plant A. ilicifolius were studied. Ampicillin and clotrimazole were used as standard anti-bacterial and anti-fungal agents, respectively. The result of the study revealed that the alcoholic and chloroform extract of the leaves exhibited strong inhibitory action against Bacillus subtilis, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus, and Aspergillus niger and moderate inhibitory action against Pseudomonas aeruginosa and Proteus vulgaris.[31]

Traditional Medicinal Uses

A decoction of the plant with sugar candy and cumin is used in dyspepsia with acid eructations. It is also considered to be a diuretic and is used as a cure for dropsy and bilious swellings. The plant is reported to be used in asthma. The leaves are expectorant, employed as an emollient fomentation in rheumatism and neuralgia. The leaves and tender shoot are used in snake bite. The root is expectorant and used in asthma. This when boiled in milk is used in leucorrhoea and general debility.

Ethnobotanical Studies

The plant is used for dyspepsia, paralysis, and asthma. The leaves are reported to be used in headache, rheumatism, and in skin diseases. Leaves and shoots are used as antidote in snake bite.[32]