ABOUT AUTHORS
Junaid Niazi1*, Yogita Bansal2, Narinderpal Kaur3
1 Asst.Prof., Bahra Institute of Pharmacy, Patiala, India
2 Assoc. Prof., Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
3 Asst. Prof., Baddi University of Emerging Sciences and Technology, Baddi, India
* niazi.junaid@yahoo.co.in
ABSTRACT
Aegle marmelos Corr., a deciduous aromatic tree has been recognized in traditional medicine for the treatment of different diseases and ailments of humans like dysentery, fever, diabetes, asthma, heart problems, ophthalmia, haemorrhoids urinary problems etc. The plant has been reported to contain several phytoconstituents belonging to category of coumarins (like marmenol), alkaloids (like aegeline), glycosides, triterpenoids, anthraquinones, sterols and volatile oils. Several modern scientific studies have authenticated its anti diarrhoeal and gastro protective, anti diabetic, antibacterial, analgesic, anti-inflammatory, antioxidant, anti thyroid, anti histaminic, anti prolifertive and anti fertility activity. Clinical trials of a formulation Diarex (containing A. marmelos has shown positive results patients suffering from diarrhoea and dysentery. This review gives a bird’s eye view mainly on folkloric uses, phytochemistry and pharmacological actions of the plant.
REFERENCE ID: PHARMATUTOR-ART-1728
INTRODUCTION
Traditional or indigenous drugs used by different ethnic groups of the world for treatment of disease have special significance of having been tested on long time scale .They are relatively safe easily available and affordable to masses. Traditional drugs have given important lead in drug research, resulting in the discovery of novel molecules. Artemisinine, theophylline, glycyretinic acid, silymarin for multi drug resistant malaria, bronchodialation, peptic ulcer treatment, hepatoprotection [1-3] have already been isolated from plants and sincere efforts for curing immunity related problems, AIDS, alzheimer’s disease and diabetes are on the way.
For variety of reasons, popularity of complimentary medicines is on increase. Traditional plant therapies coupled with dietary measures as prescribed Ayurvedic and other indigenous systems of medicines. In Australia and U.S., a sizeable population use at least one form of unconventional therapy including herbal medicines [4-5].
Aegle marmelosCorrea (syn. Feronia pellucida Roth, Cratarea marmelos L., vern. Bael, Vilwam, Kuvalam, Bengal Quince, Golden Apple, Stone Apple and Wood Apple) belonging to order Sapindales and family Rutaceae is a handsome deciduous aromatic tree growing upto 8.5 meters high and widely distributed throughout Indian peninsula along with Sri Lanka, Burma and Thailand. Stems and branches are light brown to green with axillary spines present on branches. Leaves, alternate, pale green, trifoliate; two lateral leaflets, sessile, ovate to lanceolate having reticulate pinnate venation. Flowers, greenish-white, sweetly scented,bisexual, actinomorphic, ebracteate, hypogynous, stalked; calyx, gamosepalous, five-lobed, pubescent, light green; corolla, polypetalous with 5 petals, imbricate, leathery, pale yellow from above and green from beneath; androceium , polyandrous, numerous, basifixed; gynoceium, light green, having capitate stigma and terminal style. Fruit, amphiscara (berry), yellowish green with small dots on outer surface, oblong to globose, 5.3-7.3cm in diameter, 77.2 g in weight; pulp, yellow and mucilaginous, pulp of driedfruit retains yellow colour; rind woody, 4.5 mm thick. Seeds, numerous, embedded in pulp, oblong, compressed, white, having cotton like hairs on their outer surface [6-7].
It has been valued in Ayurveda and Unani system of medicines for possessing variety of therapeutic properties. Present review will help to bridge traditional claims and modern therapy on A. marmelos.
TRADITIONAL USES
As per Charaka (1500 B.C.) bael is the best appreciated drug by the inhabitants of India. Aegle marmelos is one of the most important medicinal plants of India, Burma and Sri Lanka and in Unani system of medication [8]. The unripe dried fruits are astringent, digestive and stomachic and are prescribed to cure diarrhoea and dysentery while ripe fruits are good and simple cure for dyspepsia. Pulp of unripe fruits soaked in gingelly oil for a week is useful in removing peculiar burning sensation in soles [6]. The fruits are used in chronic diarrhoea and dysentery particularly in case of patients having diarrhoea alternating with spells of constipation. Sweet drink prepared from fruits is known to produce a soothing effect on patients recovering from bacillary dysentery. Unripe and half ripe fruits improve appetite and digestion [9]. Fruit pulp marmalade is used as prevention in cholera epidemics, piles and relieves colic flatulence [10]. Fruit is also regarded as a good dietary supplement [11]. Leaves and ripe fruits are prescribed in treatment of diarrhoeas, dysenteries, diabetes mellitus, upper respiratory tract infections and heart ailments [12-14].Leaves are regarded as a good remedy for cholera, dropsy and beriberi associated with weakness of heart [15]. Leaf decoction is said to cure asthma [13-14], effective in treating ophthalmia and other eye infections and is used as expectorant and febrifuge [10]. Inhalation of leaf juice prescribed for migraine [16]. Bark and root decoctions are used as a remedy for hypochondriasis, melancholia, palpitation and intermittent fever [12-14] [17-18]. The root bark extract of the plant has been reported to be beneficial to cure intermittent fever, mental diseases, pericarditis and angina pectoris [15] and with cumin in milk it is valued as a remedy for the poverty of seminal fluid [10].
PHYTOCHEMISTRY
A chemical literature survey of A. marmelos revealed that various plant parts such as root, bark, leaves, heartwood and fruits have number of secondary metabolites belonging to various classes of natural products.
Methanol extract of leaves of A. marmelos was reported to contain coumarin glycosides like marmenol (7-geranyloxycoumarin), scopoletin (7-hydroxy-6-methoxy coumarin) along with several other known compounds like praealtin D, N-p-cis and trans-coumaryltyramaine, montainine, trans- cinnamic acid, valencic acid, betulinic acid, 4-methoxybenzoic acid and rutaretin [19-23]. An alkaloid named (R)-(-) Aegeline, a β-hydroxyamide has been isolated from A. marmelos leaves along with various other alkaloids like N-2-[4-(3’,3’-dimethylallyloxy)phenyl]ethylcinnamide, N-2-hydroxy-2-[4-(3’,3’dimethylallyloxy)phenyl]ethylcinnamide (marmeline), N-2-hydroxy-2-(4-hydroxyphenyl)ethylcinnamide and N-4-methoxy styrylcinnamide [24-25]. Alloimperatorin (a furocoumarin) and o-isopentenylhalfordinol are also been reported from leaf extract [26]. Limonene (82.4%) and (Z)-β-ocimene (5.1%) along with p- Menth-1-en-3β, 5β-diol are the major volatile oils isolated from the A. marmelos leaves [27-28].
Methanol extract of stem bark of A. marmelos is reported to contain S-(+)-marmesin (furanocoumarin) [29] while ethanol extract of stem bark on further fractionation with petroleum ether, carbon tetrachloride, ethyl acetate and methanol yield butylated hydroxylanisole, butyl-p-tolyl sulphate, 3-methyl-4-chromanone, 5,6-dimethoxy-1-indanone, palmitic acid, methyl linoleate and 5-methoxypsoralen [30].
Methanol extract of fruit has been reported to contain a furocoumarin namely, imperatorin along with o-(3,3-dimethylallyl)halofordinol N-2-ethoxy-2-(4-phenyl)ethylcinnamide, [32] marmeline, aegeline, alloimperitorin, xanthotaxol [31-33], o-methylhalfordinol [26], umbelliferone, marmelosin, ascorbic acid and essential oils [34-36]. Fruit pulp had neutral polysaccharides containing arabinose, galactose and glucose in molar ratio 2:3:14 [37]. Bael gum polysaccharide contains d-galactose (71%), l-arabinose (12.5%), l-rhamnose (6.5%) and d-galactouronic acid (7%) [38]. Seeds have been reported to contain carbohydrates (38.5%) consisting of glucose galactose, rhamnose and arabinose and proteins (66.6%) along with a newly reported pyranocoumarin, luvangentin [39-40]. Roots are known to possess auroptene, umbelliferone, marmine, lupeol and skimmanine [36].
Structures of phytoconstituents are listed in Figure 1.
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PHARMACOLOGY
Although this plant has been widely used in various symptoms and diseases, however few pharmacological studies have been reported.
Anti diarrhoeal and Gastro protective activity
Methanol extract of unripe fruits ofA. marmelos has been reported to be effective in treating diarrhoea [41]. Unripe fruit extract in doses of 50 and 100 mg/kg intraperitoneally produced a significant inhibition of gastric lesions induced by ethanol with probable mechanism suggested for this action is involvement of prostaglandin independent mechanism of gastro-protection. At similar doses, it also significantly inhibited both the intestinal transit and the accumulation of intestinal fluid induced by castor oil in mice and also antagonized the contractile responses evoked by different agonists on guinea pig ileum in vitro [42]. Root extract treated animals showed significant inhibitory action against castor oil induced diarrhoea and found to be as effective as standard anti-diarrhoeal agents [43]. Clinical trials of a formulation DIAREX having A. marmelos has been reported on 51 patients suffering from diarrhoea with various etiologies for 7 days regularly and then weekly for eight weeks demonstrated that most of the patients started responding to drug right from 2nd day of treatment and diarrhoea was completely controlled on 2nd and 3rd days. Patients with abdominal gripping were relieved. Stool examination of patients with Entaemoeba infection showed negative result after seven days of treatment and absence of ova of Ascaris in patients suffering from ascariasis [44].
Oral administration of luvangentin, isolated from of A. marmelos seeds showed significant protection against pylorus ligated and aspirin induced gastric ulcers in rats [39].
Anti diabetic and antioxidant activity
Preliminary reports indicated that alcoholic extract of leaves of Aegle marmelos exhibited antidiabetic action in glucose-induced hyperglycaemic rats [45] and in alloxanized diabetic rats [45-47]. Hypoglycaemic and antioxidant effects of aqueous extract of A. marmelos leaves (AML) on alloxan induced diabetic rats were evaluated for four weeks. Plasma glucose levels were assayed to assess the hypoglycaemicactivity. Plasma glutathione-S-transferase (GST), erythrocyte malondialdehyde (MDA) and erythrocyte glutathione (GSH) were estimated to assess the anti oxidant activity. In the 4th week after the administration of AML there was significant reduction in blood glucose and blood urea levels along with a significant increase in GSH levels and a decrease in MDA in AML treated group. The mean GST levels that were higher in diabetic rats decreased on administration of AML [48]. Scopoletin isolated from leaves administered daily for 7 days (1.0 mg/kg p.o.) caused reduction in levels of glucose as well as hepatic glucose-6- phosphate activity along with the inhibition of hepatic lipid peroxidation and increased activity of SOD and catalase [23]. Aegeline, an alkaloid amide isolated from leaves was found to have anti-hyperglycaemic activity as evidenced by the decrease in blood glucose levels by 12.9% and 16.9% at 5 and 24 h respectively in STZ-induced diabetic rats. It also decreased plasma triglyceride (TG) levels by 55%, total cholesterol by 24% and free fatty acid by 24% along with increase in HDL by 28% and HDL- cholesterol ratio by 66% in dyslipidemic hamster model at dose of 50 mg/kg. From pharmacophoric hypothesis and 3D-QSAR model it had been suggested that compound might be a β-(3)-AR agonist [49].
Oral administration of water extract of A. marmelos fruit (125 and 250 mg/kg) twice daily to STZ-induced diabetic rats for four weeks resulted in significant lowering in blood glucose, plasma thio barbituric acid reactive substances (TBARS), hydro peroxides, plasma ceruloplasmin, α-tocopherol and increase in plasma reduced glutathione and vitamin C [50]. It had been reported that umbelliferone controls glycaemia and had a beneficial action on collagen content and its properties i.e. collagen related parameters in tail tendon which indicated recovery from risk of collagen mediated diseases of diabetes [35].
Aqueous decoction of root bark of A. marmelos also found to exhibit hypoglycaemic action in rats [51].
Aqueous extract of seed when administered in doses of 100, 250 &500 mg/kg p.o. to normal, sub diabetic (fasting blood glucose normal) and mild diabetic rats (fasting blood glucose 120-250 mg/dl) was found to be most effective in the dose of 250 mg/kg as it decreased blood glucose level by35.1% in normal healthy rats and 41.2% in sub diabetic rats and 33.2% in mild diabetic rats after 6h. Treatment of severely diabetic rats for 14 days with a dose of 250 mg/kg reduced fasting blood glucose by 60.84% and urine sugar by 75%. It also brought a fall in level of cholesterol by 25.49% with increase of 33.43% in HDL anddecrease of 53.97% and 45.77% in LDL and TG respectively [52].
Oral administration of ethanol extract resulted in significant decrease in levels of blood glucose, glycosylated haemoglobin, urea and concomitant increase in glycogen, haemoglobin and protein in STZ-induced diabetic rats. There was also increase in insulin C-peptide levels and decrease in activity of carbohydrate metabolizing enzymes like hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthetase. Increased activity of lactate dehydrogenase, fructose-1,6-biphosphatase, glucose-6-phosphatase and glycogen phosphorylase were found to decrease after administration of the extract. Increased specific binding of I125 labelled insulin to the receptor in diabetic rats got markedly reduced in extract treated diabetic rats[53].
Methanol extract of A. marmelos was found to reduce blood sugar in alloxan diabetic rats after six days of continuous administration and on 12th day blood sugar reduced by 54%. Oxidative stress produced by alloxan was significantly lowered by administration of extract. This was evident from a significant decrease in lipid peroxidation, conjugated diene and hydro peroxide levels in serum as well as liver induced by alloxan. Catalase and glutathione peroxidase activities in blood as well as liver were found to increase from 9th day onwards and superoxide dismutase (SOD) and glutathione levels on 12th day [54]. Methanol extract in dose of 100mg/ml was significantly activein increasing glucose uptake by elevating of GLUT-4, PPARγ and P-13 kinase [55]. The mechanism of anti-diabetic action of A. marmelos has not been fully understood. It has been suggested that it increases utilization of glucose either by direct stimulation of glucose uptake or via mediation of enhanced insulin secretion [45] and also decreases elevated glucose and glycosylated haemoglobin levels [56].
Effect on myocardium
A study was reported in which rats were pre-treated with A. marmelos leaf extract (AMLE) at doses of 50, 100 and 200 mg/kg orally for 35 days. After treatment period isoprenaline 200 mg/kg was administered subcutaneously to rats at interval of 24 h for two days. Pre-treatment with AMLE decreasedactivity of creatine kinase (CK) and lactatedehydrogenase (LDH) in serum and increased their activity in heart. Also pre-treatment with AMLE increased the activity of Na+-K+ -ATPase and decreased Ca2+ATPase in heart and aorta simultaneously. Levels of cholesterol and triglycerides decreased whereas levels of phospholipids in heart and aorta increased. All the deranged biochemical parameters were restored with 200 mg/ kg AMLE [56].
A linear furanocoumarin, Marmesinin showed the antioxidant activity during experimental myocardial injury. Marmesinin at a dose of 200 mg/kg orally, demonstrated a decrease in serum enzyme levels and restored the electrocardiographic changes towards normalcy, decreased the effect of lipid peroxidation and was shown to have a membrane stabilizing action by inhibiting the release of β-glucouronidase from sub cellular fractions [57]. Methanol extract of root bark of A. marmelos at a concentration of 100μg/ml inhibited the beating rate by approximately 50% in cultured mouse myocardial cells. Auropten isolated from root bark extract had IC50 of 0.6μg/ml which is comparable to verapamil [58].
Anti inflammatory, Analgesic and Anti pyretic activity
Methanol extract of A. marmelos leaves at dose of 200 and 300 mg/kg significantly reduced the writhing induced by acetic acid and exhibited significant analgesic activity in tail flick test showing that extract possessed both peripheral and central activity in mice [59]. Another study exhibited that methanol, acetone and chloroform extracts of leaves produced highly significant acute anti-inflammatory effect equipotent to Phenylbutazone at dose of 150 mg/kg intraperitoneally and also showed a significant decrease in sub acute inflammation by inhibiting cotton-pellet granuloma in rats which revealed the ability of the extract in reducing the number of fibroblasts, and synthesis of collagen and mucopolysaccharide. The extracts also produced marked analgesic activity by reducing the early and late phases of paw licking in mice. Various serial extracts of A. marmelos leaves of produced a reduction in hyperpyrexia induced by dried yeast injection comparable to that of paracetamol [60].
Anti bacterial activity
A. marmelos extracts in petroleum ether, chloroform, ethanol and water were tested on six pathogenic bacterial strains, three gram positive (Bacillus cereus, Bacillus subtilis andStaphylococcus aureus) and three gram negative (Escherichia coli, Pseudomonas vulgaris and Ps. aerogenosa) by disc diffusion method. Out of four extracts, petroleum etherextract was found to be most effective against all pathogenicstrains andactivity of petroleum extract was greater than that of streptomycin [61]. Methanol extract of fruit showed moderate activity against Escherichia coli, Salmonella typhii, Pseudomonas aeregenosa, Staphylococcus aureus, Bacillus cereus, Klebsiella aerogenes, Pseudomonas vulgaris, andShigella boydis as determined by micro broth dilution assay [62]. Hydrochloric extract of leaves of A. marmelos was found to be the most effective against Salmonella typhii by disc diffusion method [63]. Seed oil was also found to be effective bacteriostat for Vibrio cholerae, Staphylococcus aureus, andEscherichia coli [10].
Antifungalactivity
Essential oil from bael leaves was reported exhibit anti fungal activity by inhibiting mycelial growth in solid medium at a concentration of 1000-3000 ppm for certain fungi likePysalospora tucumanensis, Ceratocystis paradoxa, Sclerotium rulfsii, Curvularia lanata, Helminthosporium sacchari, Fusarium monthforme, Alternaria alternate, Alternaria brassicae, Alternaria carthami, Collelotrichum capsici, Curvularia lanata, Fusarium oxysporum, Fusarium udum, Ustilago cyanodontis and Cephalosporium sacchari and by inhibiting spore germination by diffusion testing method [64-70].
Antiviral activity
In vitroantiviral activities of series of compounds in samples extracted from various parts of bael were evaluated for the efficacy in Human Coxsackievirus B1-B6. IC50 for leaves, stem and stem bark, fruits and root, root bark and pure compound marmelide was less as compared to Ribavarin. Marmelide was isolated as the most effective virucidal agent as it interferes with early events of its replication cycle like adsorption, penetration etc [71]. A. marmelos has been reported to be strong antiviral agent against Herpes Simplex Virus-1 [72].
Anti protozoal and anti helminthic activity
Fine powder of unripe fruits showed significant effect on intestinal parasites particularly Entamoeba histolytica and Ascaris lumbricoides [10].Marmelosin isolated from the plant showed anti helmenthic activity especially against ankylostiomiasis[73].
Anti histaminic activity
Ethanol extract of leaves of A. marmelos has been reported to have a contractile effect on guinea pig isolated ileum and tracheal chain and also exerted an antagonistic effect on histamine induced contraction in dose dependent manner which might be the result of relaxant effect exerted by extract i.e. depression of H1 receptors. These studies justify the use of A. marmelos leaf extract in bronchial asthma. Lupeol, aegeline and marmesin, the effective constituents present in alcoholic extract of leaves ofA. marmelos are known to be responsible for the activity [74].
Anti fertility activity
Ethanol extract of A. marmelos leaves showed significant anti spermatogenic activity in rats [75]. Aqueous extract of A. marmelos leaf also exhibited inhibiting activity on motility of sperms in a dose and time dependent manner. Sperm motility was found out to be nil at 10% concentration of extract with in 30 seconds. It had been observed that aqueous extract ofA. marmelos leaves resisted the process of spermatogenesis and reduced sperm motility in rats [76].
Anti thyroid activity
The importance of A. marmelos leaf extract in the regulation of thyroid hormone concentration in male mice was investigated as it decreased only T3 concentration and on comparison with the control, propylthiouracil, the decrease was about 62% suggesting its possible use in the regulation of hyperthyroidism. It decreased hepatic lipid peroxidation (LPO) whereas superoxide dismutase (SOD) and catalase (CAT) activities increased, showing its antiperoxidation role [77].
Scopoletin (7-hydroxy-6-methoxy coumarin) isolated fromthe leaves of Aegle marmelos was evaluated for its potential to regulate hyperthyroidism, lipid peroxidation and hyperglycaemia in levo-thyroxine-induced hyperthyroid rats. Scopoletin at dose of 1.0 mg/kg, p.o. administered daily for 7 days to levo-thyroxine-treated animals decreased the levels of serum thyroid hormones and glucose as well as hepatic glucose-6-phosphatase activity, demonstrating its potential to regulate hyperthyroidism and hyperglycaemia. Scopoletin also inhibited hepatic lipid peroxidation and increased the activity of antioxidants, superoxide dismutase and catalase. On comparison with the standard anti thyroid drug, propylthiouracil, scopoletin exhibited a superior therapeutic activity. These findings suggest that scopoletin has the potential to inhibit thyroid function and hyperglycaemia without hepatotoxicity [23].
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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].
DISCUSSION
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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