Different activity and uses of Acanthus ilicifolius (Acanthaceae)

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.

uses

• Decoction of 30-60 g of dried material used for acute and chronic hepatitis, swelling-enlargement of the liver and spleen, swelling and enlargement of the lymph nodes, gastralgia, asthma.

• Decoction of roots and leaves used for asthma; also, to aid expectoration.

•  Root boiled in milk used for leucorrhea and general debility.

• Used for gastrointestinal pains.

• Leaves are high in mucilage and used as emollient fomentation in rheumatism.

• Young leaves used as an antidote for snake venom.

•  In India, popularly used for its wound healing effects; tender shoots and leaves used for snake bites.

•  In Malaysia, leaves used for rheumatism, neuralgia, and poison arrow wounds.

•  In Thailand, decoction of whole plant used for kidney stones.

•  In Goa, mucilaginous leaves used as emollient in rheumatism and neuralgia.

• Ground fresh bark is used as antiseptic.

•  Decoction of leaves for pain and as blood purifier.

•  In Ayurvedic medicine, it is one of 9 plants in the drug 'Sahachara,' used for rheumatic complaints.

•  Plant decoction with sugar candy and cumin used for dyspepsia with acid eructations. Also used as diuretic and cure for dropsy and bilious swellings. Leaves used for snake bites, and roots used for asthma and as expectorant. Plant boiled in milk used for leucorrhea and general debility.

In Siam and Indo-China, roots used for paralysis and asthma.
Others

         • Soap: Plant is used in the manufacture of soap; the lye prepared from the ash.

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.

Pharmacological Work

 • Anti-Hepatic Cancer:

 Study showed the aqueous leaf extract prevented hepatic DNA alterations and chromosomal damage in tumor-bearing mice. and lengthened survival. It suggests A. ilicifolius may be a potential chemoprotector against hepatic neoplasia.

• Anticarcinogenic / Tumour Reducing:

 The study found AI extract to be effective against tumor progression and carcinogen induced skin papilloma in mice. There was reduction of tumor volume and significant delay in the onset of DMBA/Croton oil-induced skin papilloma in mice in a dose-dependent manner.

• Anti-osteoporotic:

Chemical constituents of Acanthus ilicifolius L. and effect on osteoblastic MC3T3E1 cells: The study yielded a new coumaric acid derivative, acancifoliuside and six other known compounds. Tested on osteoblastic cells, it concludes that A. ilicifolius may help prevent osteoporosis.

• Anti-Inflammatory / Free Radical Scavenging Activity:

 In a study to evaluate its anti-inflammatory activity, the methanolic fraction of A ilicifolius leaf extract produced significant inhibition of rat paw edema, similar to a COX and LOX inhibitor. It also produced significant inhibition of COX 1and 2 and 5-LOX activity. It also showed significant free radical scavenging activity.

• Antimicrobial / Leaf, Stem and Roots:

Study evaluated the antimicrobial activity of ethanol, methanol, and aqueous extracts of leaf, stem, and roots of A. ilicifolius. The most active antimicrobial parts were aqueous root, ethanol stem, and methanol leaf. The ethanol extract effect was significantly higher than that produced by methanol and aqueous extracts.

• Chemopreventive / Ehrlich Ascites Carcinoma:

 Study showed treatment of EAC-bearing mice with an aqueous leaf extract resulted in restoration of hematological and hepatic histological profiles and lengthening of survival of animals against the proliferation of ascites tumor in vivo.

• Chemopreventive Activity Against Hepatocellular Carcinoma:

Study analyzed the active components of a leaf extract of A. ilicifolius. Five natural steroid compounds were compared against a synthetic drug Sorafenib and Doxorubicin on various target proteins of liver cancer.

• Antioxidant / Free Radical Scavenging Effect:

 Study confirmed the antioxidative and radical scavenging activity of an A. ilicifolius extract.

• Antioxidant / Cytotoxic / Flowers:

Flowers yielded terpenoid, phenolic compounds, and alkaloid. A methanol extract exhibited the highest antiradical efficiency against DPPH radicals and highest cytotoxicity against shrimp brine Artemia salina nauplii. Results present a potential candidate for cancer therapy.

• Antinociceptive:

A methanolic extract of Ai leaves was tested for antinociceptive activity using acetic acid-induced writhing, formalin and hot plate testing. Results showed a significant and dose-dependent antinociceptive activity in all three models.

• Gastroprotective / Anti-Ulcer:

Study evaluated the gastroprotective activity of a methanolic extract of A. ilicifolius using different models of gastric ulceration. In pylorus-ligated rats, the methanolic extract of leaves significantly reduced gastric volume, acidity, and peptic activity. Pretreatment significantly restored the levels of reduced glutathione (GSH) and SOD, CAT, and GPX, along with inhibition of both lipid peroxidation and myeloperoxidase activity. Results suggest the extract of leaves may possess anti-ulcer activities in addition to anti-inflammatory properties.

• Anti-Diabetic / Roots:

Study evaluated an ethanolic extract of roots in alloxan-induced albino Wistar rat models. Dosage of 200 and 400 mg/kg of extract significantly reduced blood glucose levels. Histopath studies showed better regeneration of ß-cells at both doses. Phytochemical analysis of roots showed the presence of flavonoids, alkaloids, terpenoids, tannins, and steroids.

• Hepatoprotective / Hepatitis B / Roots:

 Study evaluated the effect of alcohol extract on duck hepatitis B. Results showed an obvious protective effect on liver function and liver tissue. However, A. ilicifolius cannot inhibit the replication of duck hepatitis B virus.

• Anticarcinogen Against Hydrocortisone-Induced Genotoxicity:

 Study evaluated the anti-genotoxic effect of A. ilicifolius against hydrocortisone-induced genotoxicity. The extract significantly reduced the frequencies of chromosomal aberration, sister chromatid exchanges and enhancement of replication index in vitro. Results showed the Acanthus extract is highly effective in cancer prevention and quench free oxygen radicals.

• Diuretic Activity:

Study evaluated an ethanolic extract for diuretic activity. Results showed a significant increase in urine volume (P<0.01), with increase in urine electrolyte excretion of sodium and potassium.

• 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.

• 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.

• 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.

• 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.

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.

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.

• 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.

• 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.

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.

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.

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.

• Anti-Inflammatory / Free Radical Scavenging Activity:

 In a study to evaluate its anti-inflammatory activity, the methanolic fraction of A ilicifolius leaf extract produced significant inhibition of rat paw edema, similar to a COX and LOX inhibitor. It also produced significant inhibition of COX 1and 2 and 5-LOX activity. It also showed significant free radical scavenging activity.