Traditional Use, Phytochemistry, Pharmacological and Toxicological Properties of Acanthus ilicifolius: A Review ()
1. Introduction
Serendipity and man’s expedition for the drug in nature inaugurated the discovery of medicines. Nature has been an incredible cradle of medicinal agents since ages where a striking number of modern drugs have been isolated from natural sources, many of these derivations were grounded on the utilization of the agents in traditional medicine [1] . Since a long, plants have been exploited as medicines. Medicinal plant-based drug discovery continues to give new and novel therapeutics/lead compounds against various ailments like cancer, HIV/AIDS, Alzheimer, malaria, pain etc. [2] . Whole plant or plant parts basically gripped the system of crude drugs for instance tinctures, teas, poultices, powders, and other herbal formulations [3] . Traditional medicines encompass herbal medicines poised of herbs, herbal resources, herbal groundings, and finished herbal yields, that enclose as active ingredients parts of plants, or other plant supplies, or combinations thereof. Animal parts and minerals are also a part of traditional medicines [4] . The majority of the evolving world, 80% of the residents trust on these traditional medicines for major health care [5] .
Acanthus that belongs to family Acanthaceae is a genus of the topmost group angiosperms (flowering plants) embracing more than 29 species extensively disseminated in the tropical and subtropical region [6] . The term “Acanthus” is picked from the Greek word “Acantha” which means thorn or thistle indicates sensitive leaves. Acanthaceae, one of 24 families in the mint order (Lamiales) of flowering plants, containing approximately 220 genera and nearly 4000 species distributed predominantly in tropical and subtropical regions of the world. The greater part of the Acanthaceae family are herbs or shrubs, but vines and trees occur as well [7] . The range of habitats extends from marshes and estuaries to extremely dry situations, but most of these plants are found in damp tropical forests. A diverse family, Acanthaceae has few universal characteristics among its members. Most have simple leaves arranged in opposite pairs, with cystoliths (enlarged cells containing crystals of calcium carbonate) in streaks or protuberances in the vegetative parts. The bisexual flowers are frequently bilaterally symmetrical and are usually enclosed by leaflike bracts, often colored and large. Sepals and petals number five or four each and are often fused into tubular structures [8] .
Acanthus ilicifolius (Figure 1), also identified as sea holly, holly mangrove, or holly-leaved acanthus, are conventionally used in Indian and Chinese medicine. These mangroves belong to the Acanthaceae family and are 1.5 m tall vines. Conferring to Indian Ayurveda, the uses of A. ilicifolius species are convenient as nerve tonic, astringent, stimulant, and expectorant. The roots of Acanthus ilicifolius are highly indicated for the treatment of cough, asthma, leucorrhea, and paralysis. The roots and leaves are indicated against the bites of animals and insects. The mucilage of leaves aids in managing neuralgia and rheumatism [9] .
2. Methods
Scientific literatures were searched using databases like Google Scholar, PubMed,
ScienceDirect, Research Gate for traditional use, phytopharmacology and toxicology of the Acanthus ilicifolius and its pahamcological and therapeutic properties are briefly discussed in this paper.
2.1. Notable Species of Acanthus Genus
Among 29 representative species of the Acanthus genus, around six species are available in India cited A. ebracteatus Vahl, A. leucostachyus Wall, A. carduaceus Griff., A. mollis L., A. volubilis Wall. Asia and Australia represent the overriding variety and distribution of mangrove species. Consequently, the genus is inimitable amid all true mangrove genera where together true mangrove and terrestrial associates are accessible. The two subspecies of A. ebracteatus A. ebracteatus subsp. ebracteatus and A. ebracteatus subsp. ebarbatus are prevalent in Australia. Additionally, both subspecies are standing apart by few key structural features i.e. leaf outline, stem spines, floret shade and hairiness, etc. The genus was testified with one acknowledged species; A. leucostachyus from North East India which was formerly recognized by Wallich in his Numerical List of Dried Specimens (Cat. No. 2512) on the source of the assortment made by F. De Silva from Sylhet District of Bangladesh [7] .
2.2. Phytochemical Work of Acanthus ilicifolius
Different categories of chemical constituents have been sequestered and categorized from Acanthus ilicifolius. Ethanolic, Methanolic, Chloroform, Hexane extracts of different parts of the plant like root, leaves, aerial parts, stem, pods have been found to encompass diverse chemical moieties e.g., alkaloids, glycosides, lignans, triterpenoid saponins, sterols, fatty acids, and coumaric acid derivatives as summarized in Table 1 & Table 2.
2.3. Pharmacological Potential of Acanthus ilicifolius
Anti-Inflammatory Activity
Table 1. Phytochemistry of Acanthus ilicifolius.
Table 2. Compounds Isolated from Acanthus ilicifolius.
The methanolic extract of Acanthus ilicifolius plant leaf 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 extract displayed substantial anti-inflammatory activity in case of carrageenan-induced edema at 5 mg/kg i.p in rats. In acute toxicity test, the extract did not demonstrate any case of mortality in mice at doses up to 1 g/kg I [16] .
Anti-Leishmanial Activity
A compound named 2-Benzoxazolinone (BOA) was extracted from the leaves that exposed in vitro anti-leishmanial activity against Leishmania donovani. There was no case of mortality in mice when BOA was administered (i.p.) in the doses ranging from 0.25 - 1 g/kg. The LC50 value for BOA was observed to be 40 µg/ml and compared well with pentamidine [15] .
Osteoblastic Activity
A derivative of coumaric acid named acancifoliuside was secluded from the methanolic extract of the leaves. Its effects were tested on the functions of Osteoblastic MC3T3-E1 cells. It augmented the growth and differentiation of osteoblasts expressively, designating that A. ilicifolius leaves may aid to prevent osteoporosis [18] .
Hepatoprotective Activity
A significant reduction of CCl4-induced hepatotoxicity was observed followed by the oral administration of the alcoholic extract (250 and 500 mg/kg) 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. [19] .
Anti-Cancer Activity
According to Babu BH, 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 observed to exhibit cytotoxic activity towards lung fibroblasts (L-929) cells in 72 h MTT assay, and the concentration needed to cause 50% cell death was about 18 µg/ml. Furthermore, the tumor volume reduced and the life span by 75% in ascites tumor harboring animals followed by the oral administration of the extract (500 mg/kg body wt). The extract also pointedly delayed the onset of dimethyl benzanthrazene/croton oil-induced skin papilloma in mice in a dose-dependent manner [19] .
Anti-Ulcer Activity
Methanol extract of Acanthus ilicifolius leaves in experimental rats demonstrated significant inhibition of gastric lesions induced by pylorus ligation and ethanol-induced gastric ulcers. The extract displayed significant lessening in the gastric volume, free acidity, and ulcer index as compared to control. This recommends leaf methanolic extracts were found to hold anti-ulcerogenic as well as ulcer healing properties, which might be owing to anti-secretary activity [20] .
Anti-Microbial Activity
Khajure et al investigated the antimicrobial activity of the extracts of Acanthus ilicifolius demonstrated that the anti-microbial activity of alcoholic, butanolic, and chloroform extracts of leaves and roots of the plant A. ilicifolius. In that study, Ampicillin and clotrimazole were used as standard anti-bacterial and anti-fungal agents, respectively. The end result of the study discovered that the alcoholic and chloroform extract of the leaves unveiled robust inhibitory action against Bacillus subtilis, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus, and Aspergillus niger and moderate inhibitory action against Pseudomonas aeruginosa and Proteus vulgaris [21] .
Antioxidant Activity
Firdaus et al. have inspected the antioxidant properties of A. ilicifolius by the DPPH scavenging assay. The test was piloted on entire five extracts (methanol, acetone, acetone 70%, methanol 80% and water) of flowers where the extracted methanol exhibited maximum antiradical effectiveness (141.30%), whereas water extract of indicated lowermost (0.0037%) amid the extracts [22] . Flavonoids and phenolic compounds extracts of A. ilicifolius presented their good antioxidant activity on the animal model [23] .
Cytotoxic Activity
Firdaus et al. investigated the cytotoxic action of the flower extracts of A. ilicifolius on the brine shrimp lethality. The outcomes revealed methanol extract has nethermost LC50 value (22 μg/ml) while water extract exposed the peak value at 10 μg/ml amongst the extracts [22] .
Table 3 summarized the pharmacological properties of A. ilicifolius.
Table 3. Pharmacological potential of Acanthus ilicifolius.
2.4. Toxicological Studies of Acanthus ilicifolius
Acute Toxicity
According to Husori et al., all male mice groups showed no symptoms of toxicity after the administration of ethanolic extracts if Acanthus ilicifolius leaves at the doses of 1000, 2000 and 5000 mg/kg body weight. At the maximum dose, there was no death in the acute toxicity experimental animal. The above-mentioned dose did not change in general behavior or any clinical signs of toxicity [25] .
Effect on Liver
Husori et al. investigated the effect on liver by histopathological examination in mice by administering the ethanolic extract of Acanthus ilicifolius leaves at different doses. While in the group dose of 1000, 2000, and 5000 mg/kg BW, the hepatocytes initiated to experience deviations marked by the amplified infiltration of inflammatory cells, asymmetrical sinusoidal arrangement and noticeable broadening of the cell to further cover the sinusoid, but the hepatocyte has not necrosis. Infiltration of inflammatory cells did not occur in the control group, but at a dose of 1000 mg/kg BW began to be found mild infiltration and at a dose of 2000 mg/kg BW augmented infiltration of inflammatory cells and at doses of 5000 mg/kg BW severe infiltration and had formed the thrombus [25] .
Effect on Kidney
In a study of ethanolic extract of the leaves of Acanthus ilicifolius at the dose of 1000 mg/kg BW, showed the occurrence of mesangial cell proliferation but has not shown hypertrophy of glomerular tissue. But the dose of 2000 mg/kg BW showed hypertrophy of the glomerular tissue and at doses of 5000 mg/kg BW had increased the proliferation of mesangial cells, Bowman’s capsule, narrowing of tubular lumen due to enlarged cells [25] .
Effect on Pancreas
The pancreas is an essential glandular organ in the body comprising of exocrine and endocrine tissues, exocrine part consists of pancreatic acinar cells that secrete enzymes into the duodenum and the endocrine region composed of Langerhans island excrete enzymes directly into the blood [26] . In a study of the ethanolic extract of the leaves, at the dose of 2000 and 5000 mg/kg BW showed that, the glands around the Langerhans island begun to swell [25] .
Effect on Heart
Ethanolic extract of the leaves of Acanthus ilicifolius at the dose of 1000 mg/kg BW had showed no abnormality, but at the dose of 2000 mg/kg BW, had showed necrosis in heart muscle and at the dose 5000 mg/kg BW, had occurred necrosis and fatty tissue infiltration [25] .
Effect on Lung
The histologic feature of the lung after administration of ethanolic extract of the Acanthus ilicifolius leaves appeared normal. While the dose of 2000 mg/kg BW has begun thickening of the bronchial epithelium. While the dose of 5000 mg/kg BB occurs of epithelial cells damage. The results of this study indicated that the, dose up to 1000 mg/kg BW remains safe, dose of 2000 mg/kg BW cause some damage in lung tissue and dose of 5000 mg/kg BW cause toxicity on the lung tissue [25] .
The toxicological effect of the Acanthus ilicifolius is summarized in Table 4.
2.5. Ethnomedicinal Use of Acanthus ilicifolius
This plant is used to formulate Ayurvedic medicine known as Sahachara used to treat for rheumatic diseases. In Thai Traditional Medicine System, the plant is used as purgative and as an anti-inflammatory, the leaves are mixed with pepper (Piper nigrum L) as tonic pills. It is also employed as an emollient for rheumatism and neuralgia [27] . It is believed among mangrove habitats that chewing the leaves cause protect against snake bites [28] . Tea prepared from the leaves relieves pain and purifies blood [29] . A decoction of the plant with sugar candy and cumin is used in dyspepsia with acid eructation. Leaves are pounded and
Table 4. The toxicological effect of the Acanthus ilicifolius.
soaked in water for external application and also used as an expectorant [30] . Traditional medicinal practitioners claim that this plant is useful in the treatment of asthma, diabetes, dyspepsia, hepatitis, leprosy, neuralgia, paralysis, ringworm, skin disease, snake bite, leukemia [27] .
3. Conclusion
The plants belonging the genus Acanthus are extensively sprinkled in the tropical and subtropical provinces of the globe. The methodical pharmacological studies regarding Acanthus ilicifolius have assumed incredible appreciation to their ethnomedicinal uses in the management of health care. Study of the literature revealed that, Acanthus ilicifolius is an important medicinal plant with diverse pharmacological activities. Additionally, scanty and inadequate toxicological information on the animal model is currently existing, which proposes that meticulous toxicological estimation is needed for different extracts of different parts of this plant. Furthermore, the biological efficacy studies should be conducted for the extracted secondary metabolites as well, which could validate the remedial claims of Acanthus ilicifolius.