Aegle marmelos: A phytochemical and phytopharmacological review

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Anti proliferative and Radio protective activity
It had been revealed that various extracts of stem bark of Aegle marmelos Corr. were able to inhibit the in-vitro proliferation of human tumour cell lines, including the leukaemic K562, T-lymphoid Jurkat, B-lymphoid Raji, erythroleukemic HEL, melanoma Colo38, and breast cancer MCF7 and MDAMB-231 cell lines. Molecules present within the A. marmelos extracts were identified by gas-chromatography/mass-spectrometry analysis; three derivatives (butyl p-tolyl sulphide, 6- methyl-4-chromanone and butylated hydroxyanisole) were found to exhibit strong activity in inhibiting in vitro cell growth of human K562 cells. The anti proliferative activity of these compounds was comparable to that of known anti tumour agents, including Cisplatin, Chromomycin, Cytosine arabinoside and 5-fluorouracil. In addition, the anti proliferative activity of butyl-p-tolyl sulphide, 6-methyl-4-chromanone and 5-methoxypsolaren was associated to activation of the differentiation pattern of K562 cells [30].

The anticancer effect of hydro alcoholic extract of Aegle marmelos (AME) was studied in the Ehrlich Ascites Carcinoma bearing Swiss albino mice. The spatial effect of various AME administration schedules showed that six-day administration increased the survival of tumour bearing mice. The best anti neoplastic action of AME was observed on its intraperitoneal route. Administration of AME once daily for six consecutive days to the tumour bearing mice caused a dose dependent remission of the tumour at 400 mg/kg body weight, where the greatest anti tumour effect was observed and the higher doses showed toxic manifestations. A 24 day lengthening in life span was observed in EAC animals treated with 400 mg/kg AME. This dose of 400 mg/kg was considered as the best dose, where the animals survived upto 43 day post-tumour-cell inoculation as against no survivors in the saline treated control group. The AME treatment resulted in a dose dependent elevation in the median survival time (MST) and average survival time (AST) up to 400 mg/kg AME and declined thereafter. The effective dose of 400 mg of AME was 1/6 of the LD50 dose, which increased the MST and AST up to 29 and 27 day, respectively [78].

The radio protective effect of hydro alcoholic extract of leaves of Aeglemarmelos (AME) was evaluated in cultured human peripheral bloodlymphocytes (HPBLs) by the micronucleus assay. The optimum protectivedose of the extract was selected by treating HPBLs with1.25,2.5, 5, 6.25, 10, 20, 40, 60, 80 and 100 µg/ml AME beforeexposure to 3 Gy -radiation and then evaluating the micronucleusfrequency in cytokinesis blocked HPBLs. Treatment of HPBLs withdifferent doses of AME reduced the frequency of radiation-inducedmicronuclei significantly, with the greatest reduction in micronucleusinduction being observed for 5 µg/ml AME. The irradiation of HPBLs withdifferent doses of γ -radiation caused a dose-dependent increasein the frequency of lymphocytes bearing one, two and multiplemicronuclei, while treatment of HPBLs with 5µg/ml AMEsignificantly reduced the frequency of lymphocytes bearing one,two and multiple micronuclei when compared with the irradiatedcontrol. The dose–response relationship for both groupswas found out to be linear. AME was foundto inhibit free radicals in a dose-dependent manner up to adose of 200µg/ml [79].

The radio protective effect of a hydro alcoholic extracted materialfrom the fruit of Aegle marmelos (AME) was studied in mice exposedto different doses of γ-radiation. The optimum dose for radio protectionwas determined by administering 0, 5, 10, 20, 40, or 80 mg/kgbody weight of AME intraperitoneally once daily, consecutivelyfor 5 days before exposure to 10 Gy of γ-radiation. A total of20 mg/kg of AME for 5 consecutive days before irradiationwasfound to afford maximum protection as evidenced by the highestnumber of survivors after 30 days post irradiation. Animals fromall groups were monitored for 30 days post irradiation for developmentof symptoms of radiation sickness and mortality. Treatment ofmice with AME before exposure to different doses of γ radiation reduced the severity of symptoms of radiation sickness and mortalitywith all exposure doses. Treatment of animals with AME before irradiation causeda significant decrease in the lipid peroxidation accompaniedby a significant elevation in the GSH concentration in liver,kidney, stomach, and intestine of micedeterminedafter 31 dayspost irradiation [80].

Anti thalessemic activity
Extract of A. marmelos has been reported to stimulate the production of fetal haemoglobin in adults and can be used as a possible remedy for β-thalassemia [81].

Antimicroflarial activity
A study has explored that methanolic extracts of leaves of A. marmelos Corr. has antifilarial effect against Brugia malayi microfilariae as it was observed that leaves extract at 100 ng/ml concentration showed complete loss of motility of microfilariae after 48 hr of incubation. Coumarin in the leaves of A. marmelos Corr. are known to be responsible for the activity [82].

Larvicidal activity
Aegle marmelos has been reported to possess moderate larvicidal activity against early fourth-instar larvae of Culex quinquefasciatus [83].

Wound healing activity
The root bark extract of Aegle marmelos was found to promote wound healing in both normal and immunocompromised (steroid treated) rats in a space wound model. The plant increased not only lysyl oxidase activity but also, protein and nucleic acid content in the granuloma tissue indicating it probably exert their action at the cellular (nuclear) level. It also increased the tensile strength of the granuloma tissue due to the result of the increase in the glycosaminoglycan content. Thus A. marmelos root bark not only hastened normal healing, but also reversed steroid depressed healing [84].

Effect on enzyme kinetics
Leaf extract of Aegle marmelos was found to significantly reverse the raised Km values, but not Vmax values of the enzyme malate dehydrogenase, an important enzyme in glucose metabolism [85].

Abortifacient activity
Aqueous extract of A. Marmelos leaves has been reported to exhibit significant abortifacient activity in rats [86].

Anti amnesic activity
A study was undertaken in which Chywanprash (containing A. marmelos as one of the ingredient) at the dose of 1 and 2% w/w of diet administered daily for 15 successive days in mice with memory deficits. The administration of Chywanprash for 15 consecutive days significantly protected the animals from developing memory impairment. Furthermore, there was a significant decrease in brain TBARS and increase in GSH levels after administration of Chywanprash (2% w/w), thereby indicating decreased free radical generation and increased scavenging of free radical, respectively [87].

Toxicity studies
The acute toxicity study of AME showed that the drug is non-toxic up to a dose of 1750 mg/kg body weight. The LD10 and LD50 were found to be 2000 and 2250 mg/kg respectively [78].

From the times immemorial, plants have been used as curative agents for variety of ailments.Aegle marmelos preparations are widely available and employed by practitioners of natural health for treatment of diarrhoea, diabetes, inflammation, asthma, fever, ophthalmia, heart problems and to cure poverty of seminal fluid. Most of the studies have been conducted on crude preparations of A. marmelos without mention of their chemical profile. Although the studies of A. marmelos have proved its efficacy in several complications but the detailed research work on isolation of bio actives through clinical trials followed by standardization is seriously required. There have been reports on the clinical uses of A. marmelos which have shown promising results as the plant A. marmelos has a wide array of pharmacological activities and many isolated compounds of A. marmelos lack study on their pharmacological activity.

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