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Indo American Journal of Pharmaceutical Research, 2013 Journal home page: http://www.iajpr.com/index.php/en/ ISSN NO: 2231-6876 INDO AMERICAN JOURNAL OF PHARMACEUTICAL RESEARCH A REVIEW: TREMENDOUS PHARMACOLOGICAL WORTH OF AEGLE MARMELOS Hiral K. Modi*1, Vishnu Patel2 1 2 Research Scholar, JJT University, Jhunjhunu, Rajasthan-333001, India APMC College of Pharmaceutical Education & Research, Himmatnagar, Gujarat, India ARTICLE INFO Article history Received / /2013 Available online 31/08/2013 Keywords Aegle marmelos, Rutaceae, Antidiabetic, Anti ulcer, Wound healing. ABSTRACT Aegle marmelos (L.) is one of the important herbal plant with several medicinal and nutraceutical properties. From ancient immorial, plants & their products have been used to treat multiple ailments. Today, fast moving generation wants allopathic drugs for fast response but other darkest side of side effect of this allopathic drug. Hence, natural plants are good alternatives because lack or less side affects with similar efficacy to cure the disease from origin. The present study is based on the pharmacological activity of Aegle marmelos, commonly known as a bael in India. This plant is having great potential to cure the disease like diabetes, cholesterol, peptic ulcer, inflammation, diarrhea, and dysentery, anticancer, cardio protective, anti bacterial, anti fungal, anti pyretic, analgesic, radio protective, constipation, respiratory infection, antioxidant, wound healing and many more. In this review summarizes the scientific background information of various aspects of Aegle marmelos plant used in traditional medical system for cure the variety of diseases. Corresponding author Copy right © 2013 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Page Please cite this article in press as Hiral K. Modi et.al. A review: tremendous pharmacological worth of Aegle marmelos. Indo American Journal of Pharm Research.2013:3(8). 6044 Hiral K. Modi Research Scholar, JJT university, Jhunjhunu, Rajasthan-333001,India Email ID: [email protected] Contact No: +91 9428281543 Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 INTRODUCTION A survival of human being on the earth is not possible without use of natural constituents. This is very true belief that Natural Plants are very healthier & energetic, mostly safer rather than synthetics (Allopathic Medicines). In India, medicinal plants are considered as wide source of active pharmacological constituents which used in multiple ailments in home. A diversity of herbal plants can be used in management of various disorders. The present documentary study on indigenous tremendous uses of Aegle marmelos which explore its ethanopharmacological property. Aegle marmelos is a fruit-bearing tree indigenous to dry forest on hills and plains of central and southern Asian countries & belongs to the family Rutaceae (Citrus Fruits Family). The Bael tree has its origin from Eastern Ghats & Central India. It is mainly found in tropical & subtropical Regions. Bael is found to growing along foothills of Himalaya, Uttaranchal, Jharkhand, and Madhya Pradesh along the east coast. It has many Indian names, depending on the geographical region or the language as shown in Table 1. [1]. Different parts of A. marmelos have been investigated by several workers and found to contain coumarins, alkaloids, triterpenes, sterols and essential oils & flavonoids. [2]. A detail about ethanomedical uses of different parts of plant shown in Table 2. Table 2: Different Phytoconstituents in Aegle marmelos www.iajpr.com Page Free radicals are found to be responsible for the toxic effects of xenobiotics. Flavonoids are a family of antioxidants that protect the cell from oxidative stress. Flavonoids and phenolic compounds, which have been reported to exert multiple biological effects, including antioxidant, free radical scavenging abilities, antiinflammatory activity, anti carcinogenic activity etc. Flavonoids used for the prevention and cure of various diseases which is mainly associated with free radicals. The plant is of very high value in treating cardiac disorders, dysentery, diarrhea, diabetes, fever, inflammation, and pain.[3] The anticancer, antihyperglycemic, anti-inflammatory, antipyretic, analgesic and chemo protective activities of the leaves of the plant have also been studied.[4] The leaves of Aegle marmelos are useful as laxative, febrifuge and expectorant, also in ophthalmia, deafness, inflammations, catarrh, diabetes, and asthmatic and antifungal complaints. The roots, in the form of a decoction, are used to treat melancholia, intermittent fevers and heart palpitations. [5] The bitter tasting leaves are used as a febrifuge and a poultice made of them is used for ophthalmic disorders and ulcers. Fresh leaves have been used to treat weakness of the heart, dropsy and beri-beri. Bengal quince has also been used for stomach ache, snakebite, cholera, convulsions, dyspepsia, malaria, nausea, spasms, thirst, tumors, sores, itches and proctitis and as an abortifacient. It also finds use as an anodyne, astringent, dentifrice, digestive, pesticides, refrigerant, restorative and laxative. 6045 Table 1: Different Vernacular Names of Aegle marmelos Language Vernacular Different Names Hindi Bael, Bel, Belgiri Sanskrit Bilva, Shivdruma, Shivphala English Bengal Quince Urdu Belk, Belk ham Gujarati Bilvaphala Malayalam Marredy Tamil Vivla Marum , Vivama Vol 3, Issue 8, 2013. Hiral K. Modi et al. Part Leaf Bark Fruit Seed ISSN NO: 2231-6876 Phytoconstituents Skimmianine, Aegeline, Lupeol, Cineol, Citral, Citronella, Cuminaldehyde, Eugenol, Marmesinine Skimmianine, Fagarine, Marmin Marmelosin, Luvangetin, Aurapten, Psoralen, Marmelide, Tannin Essential oil: D-limonene, A-D-phellandrene, Cineol, Citronellal, Citral, P-cyrnene, Cumin aldehyde www.iajpr.com Page Antiulcer Activity Ulcer develops when there is imbalance between the aggressive (acid secretion) factors & defensive factors (mucosal lining). H.pylori infection, NSAIDS & stress main causative factors which lowering mucosal protection in inner lining of GI tract. Goel RK et al. reported that oral; administration of pyranocoumarin isolated from the seeds of Aegle marmelos Correa, showed significant protection against pylorus-ligated and aspirin-induced gastric ulcers in rats and cold restraint stress-induced gastric ulcers in rats and guinea pigs.[10] 6046 Tremendous approved pharmacological activity of Aegle marmelos Antidiabetic activity Diabetes mellitus is metabolic disorder which independent risk factor for coronary artery disease, hypertension, myocardial infaraction & hyperlipidemia. Diabetes & its related complication are closely related with free radical induced oxidative stress. Any antidiabetic drug can acts via multidirectional either by increase in glycogen storage or increase in insulin production & by these means significantly decrease the blood glucose level. Mostly leaves & fruits of Aegle marmelos are frequently investigated. Aqueous extract of Aegle marmelos leaves, was evaluated for hypoglycemic and antioxidant effect by Upadhya S using alloxon induced diabetes in male albino rats and proposed AML may be useful in the long-term management of diabetes. There was a decrease in blood glucose at the end of 4 weeks in treated animals compared with diabetic rats. There was an increase in erythrocyte GSH and a decrease in MDA in treated animals. [6] Narender T et al., investigated antihyperglycemic and antidyslipidemic activity in sucrose challenged streptozotocin induced diabetic rats (STZ) model at the dose of 100 mg/kg body weight. From the leaves of Aegle marmelos an alkaloidal-amide, Aegeline 2, was isolated and found to have antihyperglycemic activity as evidenced by lowering the blood glucose levels. Oral administration of the water extract (125 and 250 mg /kg) twice a day for 4 weeks resulted in significant reductions in blood glucose, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and α-tocopherol and a significant elevation in plasma reduced glutathione and Vitamin C in diabetic rats.[7] Kesari AN et al., has found hypoglycemic activity of aqueous extract of Aegle marmelos seeds at 250 mg/kg dose decreases blood glucose level (BGL) by 35.1% in normal healthy rats after 6 h of administration. Treatment of severely (FBG >250 mg/dl) diabetic rats for 14 days with a dose of 250 mg/kg reduces the fasting blood glucose and urine sugar by than their pretreatment levels. It brought about fall in level of total cholesterol (TC) by with increase of in high density lipoprotein (HDL) and decrease of and in low density lipoprotein (LDL) and triglyceride (TG), respectively.[8] Kamalakannan et al., exhibited better hypoglycemic effect of fruit extract of Bael at a dose of 250 mg/kg more effective than glibenclamide, a well-known hypoglycemic drug. This antidiabetic effect is probably due to the presence of Coumarins in the fruit extract, which potentiate the insulin secretion from existing beta cells of the isles of langerhans.[9] Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 Dhuley JN et al., reported that pretreatment of rats with unripe bael fruit extract produce a significant inhibition of absolute ethanol induced gastric mucosal damage. This activity may be due to the compound Luvangetin present in the fruit.[3] Gastric ulcer is basically mediated by the development of oxidative stress and the compounds preventing ulcer formation may act through inhibition of oxidative stress in the gastro duodenal mucosa. The phenolic compounds are potent antioxidants and have powerful antiulcer activities.[11] Phoolsingh BV investigated the therapeutic use of Aegle marmelos in Inflammatory bowel disease (IBD), clinically characterized by bloody diarrhea, cramping and abdominal pain, is an immunologically mediated chronic and relapsing inflammatory disease affecting the lining of the intestine. Studies have shown that feeding a single dose of methanolic extract of bael (200 mg/kg), ameliorated DNBS-induce ulcerative colitis in rats. Bael inhibited the DNBS-induced decrease in food and water intake, wasting and restored the stool consistency. Bael reduced the gross changes, mucosal damage and disease activity index. Histopathological study showed that bael administration decreased infiltrative neutrophil and inflammation. The biochemical assays showed a decrease in the levels of NO, LPx and MPO. Concomitantly the levels of antioxidant enzyme in the bael treated colitis cohort were increased. [12] Page Antimicrobial Activity Various extracts of Bael leaves, roots and fruits have been reported to be active against many bacterial strains. Leaf extract have shown activity against Escherichia coli. The essential oil obtained from the leaves exhibited activity against E. coli, Pseudomonas salanacearum and Xanthomona Vesicatoria. Maheshwari et al, studied on ethanolic extract of dried fruit pulp of Aegle marmelos against various intestinal pathogens i.e. Shigella boydii, S. sonnei & S. Flexneri and proposed that certain photochemical including Phenols, Tannins and Flavonoids were effective against all. It was also confirmed by getting treat E. coli with Aegle marmelos fruit extract. [17] 6047 Analgesic Anti-Inflammatory & Antipyretic Activity Inflammation is attributed to release of histamine & serotonin in initial phase. The second phase characterized by release of prostaglandins. Any Anti inflammatory drug which directly or indirectly affect arachnoids metabolism pathway & reduce the release of prostaglandins. Different organic extracts of the Bael leaves possess highly significant acute and sub acute anti-inflammatory analgesic and antipyretic activities. Arul V et al., studied serial extracts of the leaves of Aegle marmelos Corr. for anti-inflammatory property. The analgesic and antipyretic properties were also evaluated. The most of the extracts derived from the plant Aegle marmelos caused a significant inhibition of the carrageenan-induced paw oedema and cotton-pellet granuloma in rats. The extracts also produced marked analgesic activity by reduction the early and late phases of paw licking in mice. A significant reduction in hyperpyrexia in rats was also produced by the most of the extracts.[13] This activity may be due to the presence of some anti-inflammatory and anti-allergenic constituents, such as Lupeol and Citral present in the alcoholic extract, as most of the anti-inflammatory and anti-allergenic compounds act through inhibition of histamine mediated signaling.[14] Ghangale GR evaluated aqueous extract of Aegle marmelos for anti inflammatory activity by using rat paw oedema model and proposed that Aegle marmelos possesses anti-inflammatory activity.[15] Shankharananth V demonstrated that methanolic extract of leaves of Aegle marmelos at a dose level of 200 and 300 mg/ kg show significant analgesic activity on acetic acid induced writhing and tail flick test in mice.[16] www.iajpr.com Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 Citarasu et al, also experimented Aegle marmelos on certain pathogenic bacteria like Salmonella typhi, Pseudomonas aeruginosa, Aeromonas hydrophyla & Vibrio sp., and concluded its positive bactericidal effects.[18] Methanol and aqueous extract of Bael fruit have shown strong activity against multidrug resistant S. typhimurium. Methanolic extract is more potent than the aqueous extract. The minimum inhibitory concentration (MIC) value of the methanolic extract is around 256 μg/ml. The unsaponifiable matter of the seed has shown considerable in vitro activity against E. coli, S. typhi, Salmonella paratyphi, Proteus vulgaris, Streptococcos faecalis, V. cholerae, Klebsiella pneumoniae, P.aeruginosa and Neisseria gonorrhoeae.[19] Bael has antibacterial activity and the mechanism of action may be the blockage of protein synthesis either at transcription or translation level and /or peptide-glycan synthesis at membrane level. The antibacterial activity of leaf extract may be due to the presence of Cuminaldehyde and Eugenol because these compounds have already shown their activities against various bacterial strains [20]. www.iajpr.com Page Anti Asthmatic Activity Asthma is chronic disorder of respiratory tract which associate with bronchoconstriction by release of histamine. Arul V et al., studied effect of the alcoholic extract of the leaves of Aegle marmelos Corr. on guinea pig isolated ileum and tracheal chain. As this plant is used traditionally to treat asthma and related afflictions. 6048 Antifertility Activity It is known that the structure and function of the epididymis are dependent on androgens. A dose-dependent suppression of cauda epididymal sperm motility and density suggested an undersupply of testosterone to epididymis and caused impaired epididymal function. This impaired epididymal function may also be due to the reduced activity of the testes, which affects the normal passage of testicular fluid into the epididymis. Adenosine triphosphate (ATP) is the source of energy for sperm motility. Any drug treatmewnt which possibly inhibited the activity of ATP in spermatozoa by uncoupling oxidative phosphorylation from the respiratory chain and preventing phosphorylation of adenosine diphosphate to ATP thus rendering the spermatozoa immotile. Sathiyaraj K et al., evaluated the effective concentration of aqueous extract of Aegle marmelos leaves on male reproductive system of albino rats for antifertility activity. Significant decreases in the weights of testis, epididymis and seminal vesicle were observed. A dose related reduction in the testicular sperm count, epididymal sperm count and motility and abnormal sperm count were observed. [21] Chauhan A et al., studied the antifertility potential of ethanolic leaf extract of Aegle marmelos on the reproductive system of male albino rats. Marked reduction in motility and density of the sperm derived from cauda epididymis of the treated animals was observed and suggested an undersupply of testosterone to epididymis and caused impaired epididymal function. This impaired epididymal function may also be due to the reduced activity of the testes, which affects the normal passage of testicular fluid into the epididymis. Aegle marmelos reduced fertility of male rats by 100% at the 300-mg dose level. [22] Das UK et al., investigated the effect of aqueous extract of leaf of Aegle marmelos (Bael) at the dose 50 mg/100 g body weight resulted a significant diminution in the activities of key testicular steroidogenic enzymes along with low levels of plasma testosterone and relative wet weights of sex organs in respect to control without any significant alteration in general body growth. Germ cells numbers in different generation at stage VII of seminiferous epithelial cell cycle were diminished significantly after the treatment of the above extract. The above mentioned dose did not exhibit any toxicity in liver and kidney. Therefore, it may be predicted that the aqueous extract of leaf of Aegle marmelos has a potent anti testicular effect at a specific dose. [23] Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 These effects were investigated using the isolated organ bath method. Alcoholic extracts elicited the antagonistic effect against histamine and also relaxed the histamine-induced contractions, it can be concluded that relaxations induced by Aegle marmelos in both guinea pig ileum and tracheal chain were due to the depression of H1- receptors. [24] Anticancer Activity Costa LV et al., evaluated the anticancer potential of folk medicine used in Bangladeshi and used extracts of Aegle marmelos for cytotoxic action using brine shrimp lethality assay; sea urchin eggs assay, and MTT assay using tumor cell lines. The extract of Aegle marmelos was found to exhibited toxicity on all used assays.[25] Bael inhibited in vitro proliferation of human tumor cell lines including the lecukenic K562, Lymphoid jurhat, Beta lymphoid Raji, Erythro leukemic HEL.[26] Antihyperlipidaemic Activity Hyperlipidemia is characterized by increase in Cholesterol & Triglycerides in blood. Rajadurai M et al., studied antihyperlipidemic activity by pretreatment with Bael leaf extract at 100 mg/kg and 200 mg/kg doses for 35 www.iajpr.com Page Anti thyroid Activity Panda S et al., isolated, Scopoletin (7-hydroxy-6-methoxy coumarin) from Aegle marmelos leaves and evaluate for its potential to regulate hyperthyroidism. It was observed that Scopoletin (at 1.00 mg / kg, p.o. for 7 days) to levo-thyroxine treated animals, decreased serum thyroid hormones level. It was also proved that the Scopoletin have superior therapeutic activity than the standard antithyroid drug, propylthiouracil.[30] Leaf extract (1 gm/kg) of A. marmelos was investigated in the regulation of thyroid hormone in male mice. While serum level of both T3 and T 4 were inhibited by extract of A. marmelos could decrease only T3 concentration about 62% indicating its possible use in the regulation of hyperthyroidism. [31] 6049 Radio Protective Activity The radio protective effect of hydro alcoholic extract of Bael leaves has been evaluated in cultured human peripheral blood lymphocytes (HPBLs). The irradiation of HPBLs with different doses of gamma-radiation caused a dose-dependent increase in the frequency of lymphocytes bearing one, two and multiple micronuclei. Treatment of HPBLs with 5 μg/ml leaf extract significantly reduced the frequency of lymphocyte bearing one, two and multiple micronuclei when compared with the irradiated control. The mechanism of this type of radio protective activity of the leaf extract may be due to the scavenging of radiation –induced free radicals.[27] Symptoms of sickness and mortality of the animals are due to irradiation resulting in a dose-dependent elevation in lipid per oxidation in liver, kidney, stomach and intestine as well as depletion in GSH concentration. Treatment of the Bael fruit extract before irradiation caused a significant decrease in the lipid per oxidation accompanied by a significant elevation in the GSH concentration in liver, kidney, stomach and intestine of mice.[28] Jagetia GC et al., investigated the radio protective effect of Aegle marmelos extract by exposing to different doses of gamma-radiation in mice and found that oral administration of extract resulted in an increase in radiation tolerance by 1.6 Gy. Also studied effects of plant extract on the peripheral blood and small intestine of Swiss albino mice. They exposed the animals to gamma radiation and data were collected against radiationinduced changes in the peripheral blood, spleen colony forming units, and intestinal mucosa, reported that Aegle marmelos extract significantly reduces the deleterious effect of radiation in intestine and bone marrow of mouse.[29] Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 days. Leaf extracts shown significant improvement on the activities of marker enzymes, decrement of lipid peroxides, plasma lipids and lipoproteins in isoproterenol-treated rats, suggesting its antihyperlipidemic effect. [32] Vijaya C et al., investigated hypolipidemic activity by ethanolic extract of Bael leaves extracts inhibited the elevation of serum cholesterol and triglycerides level in triton WR 1339 treated hyperlipidaemic rat. This extract also potentiates glucose utilization. The higher level of fatty acid and their metabolites such as acyl carnitine and long chain acyl CoA usually interfere with NA+/K+ ATPase activity level.[33] Cardio Protective Activity Prince PS et al., evaluated the preventive effects of an aqueous Aegle marmelos leaf extract in isoprenaline (isoproterenol) - induced myocardial infarction in rats. Pretreatment with leaf extract decreased the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum and increased them in the heart, also increased the activity of Na+K+ATPase and decreased the activity of Ca2+ATPase in the heart and aorta simultaneously and the levels of cholesterol and triglycerides decreased whereas phospholipids increased in heart and aorta of leaf extracts-pretreated rats. [34] Anti Malarial Activity Protozoal disease like malaria is of the most troublesome problems in tropical countries. Malaria caused by Plasmodium falciparum causes about 2 million deaths annually.[35] Development of resistance to existing antimalarial drugs has led to complications in treating this dreadful disease Thus, identification of novel molecules to treat this multidrug resistant malaria is vital. [36] www.iajpr.com Page Antifungal Activity The essential oil isolated from the leaves of Bael tree has proved to antifungal activity against animal and human fungi like Trichophyton mentagrophytes, T. rubrum, Microsporum gypseum, M. audounii, M. cookie, Epidermophyton floccosum, Aspergillus niger, A. flavus and Histoplasma capsulatum. The germination of any spore (that is bacterial or fungal) is related to Ca+2 –dipicolonate and /or free Ca+2 ions availability in the medium as well as within by spore is one of the prime factors that determine whether the spore will germinate or remain dormant. The essential oil from the Bael leaves may interfere with the Ca+2 –dipicolonic acid metabolism pathway and possibly inhibit spore germination. Thus it exhibits the antifungal activity by lowering 6050 Thus, identification of novel molecules to treat this multidrug resistant malaria is vital. The alcoholic extracts of the Bael seeds and leaves have been tested in vivo and in vitro for antimalarial activity against the NK65 strain of Plasmodium berghei. The seeds have shown schizontocidal activity in both the system, whereas, the leaves have shown activity only in the in-vitro system.[37] Wound Healing Activity Jaswant A et al., investigated effect of topical and intraperitoneal administration of methanolic extract of Aegle marmelos ointment and injection was studied respectively on two types of wound models in rats, the excision and the incision wound model. Both the injection and the ointment of the methanolic extract of Aegle marmelos produced a significant response in both of the wound type tested. In the excision model the extract treated wounds were found to epithelialize faster and the rate of wound contraction was higher, as compared to control wounds. The extract facilitated the healing process as evidenced by increase in the tensile strength in the incision model. [38] Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 the vegetative fungal body inside the host or in solid medium. This is the possible mechanism of the protective role of Bael leaf oil against fungal infection. [39] Ocular Activity Agarwal R et al., have shown that administering the unripe fruit extract (1%) reduces the intraocular pressure caused by water loading and steroids in the in the New Zealand white rabbits. The efficacy was comparable to that of timolol, a standard clinically used drug after 45 min of water loading in the water loading model, and during the first 2 h of treatment in the steroid-induced model. These results clearly suggest that bael fruit extract was effective in lowering the experimentally-induced intraocular pressure in experimental animal models and has the potential to be of pharmaceutical use. [40] www.iajpr.com Page Toxicological Studies Total alcoholic, total aqueous, whole aqueous and methanolic extracts were collected from the leaves of A. marmelos and studied in experimental rats for their toxicity. No histopathological changes were found when extracts of A. marmelos were administered intraperitoneally for 14 days successively at the dose of 50 mg/kg 6051 Antidepressant Activity Kothari S., investigated the anxiolytic and antidepressant activities of methanol extract of Aegle marmelos leaves as well as its interaction with conventional anxiolytic and antidepressant drugs using elevated plus maze and tail suspension test in mice. Albino mice were treated with AM (75, 150 and 300 mg/kg, po), imipramine (20 mg/kg, po), fluoxetine (20 mg/kg, po), and combination of sub-effective dose of AM with imipramine or fluoxetine. Effects were observed on time spent on, number of entries into, number of stretch attend postures, number of head dips in arms of elevated plus maze and on duration of immobility in tail suspension test. Effects of extracts (75, 150 and 300 mg/kg po) were observed on locomotor activity using photoactometer. Results showed that extracts significantly (P<0.05) and dose dependently increased proportionate time spent on and number of entries into open arms while decreased number of stretch attend postures and head dips in closed arms. Dose dependent and significant (P<0.05) anti-immobility effect was found in mice treated with extract. Combination of extract (75 mg/kg, po) with imipramine (5 mg/ kg, po) or fluoxetine (5 mg/kg, po) also produced significant (P<0.05) anxiolytic and antidepressant activity. Methanol extract showed insignificant (P>0.05) effect on locomotor activity of mice. It is concluded that extract possess potential anxiolytic and antidepressant activities and it enhances the anxiolytic and antidepressant activities of imipramine and fluoxetine. [41] Immunomodulatory Studies The aim of the present study was to investigate the immunomodulatory action of methanolic extract of Aegle marmelos fruit (FEAM) in experimental model of immunity. Cellular immunity was carried out by neutrophill adhesion test and carbon clearance assay, whereas, humoral immunity was analyzed by mice lethality test and indirect haemagglutination assay. Both high and low doses of FEAM significantly prevented the mortality induced by bovine Pasteurella multocida in mice. Treatment of animals with FEAM and OSE significantly increased the circulating antibody titer in indirect haemagglunation test. Among the different doses, low one was more effective in cellular immunity models than the high. However, all the doses exhibited similar protection in humoral immunity procedures. From the above findings, it is concluded that FEAM possesses potential for augmenting immune activity by cellular and humoral mediated mechanisms more at low dose (100 mg/kg) than high dose (500 mg/kg).[42] Vol 3, Issue 8, 2013. Hiral K. Modi et al. ISSN NO: 2231-6876 body wt. The collected data demonstrate that the extracts of the leaves of A. marmelos have a high margin of drug safety.[43] Other Activities Bael plant acts as a ‘Sink’ for chemical pollutants as it absorbs poisonous gases from atmosphere and make them inert or neutral. It is a member of plant species group known as ‘Climate Purifiers’, which emit greater percentage of oxygen in sunlight as compared to other plants. The tree is also consider under the category of ‘Fragrant’ species, whose flowers and volatile vapours neutralize bad smell of petrified organic matter or decaying refuge and thus save human life from bacterial attack by making them inert and deodorizing the bad odour of air.[44] www.iajpr.com Page REFERENCES 1. Pattanayak P, Mohapatra P, Phytopharmacology of Aegle marmelos (L.) CORREA. Pharmacognosy Reviews 2008; 2(4): Supplement. 2. Siddique NA, Mujeeb M, Ansari SH, Ahmad S, Development of quality standards of Aegle marmelos Leaves. Journal of Phytology 2010; 2(2): 36–43. 3. Dhuley JN, Investigation on the gastroprotective and antidiarrhoeal properties of Aegle marmelos unripe fruit extracts. Hindustan Antibiotics Bulletin 2007; 41: 45-46. 4. Shaheen F, Fatima F, Sadia R, Aneela N, Fatima N et al., Shahidine, a novel and highly labile oxazoline from Aegle marmelos: the parent compound of aegeline and related amides. Tetrahedron 2009; 65: 998– 1004. 5. Rana BK, Singh UP, Taneja V, Antifungal activity & kinetics of inhibition by essential oil isolated from leaves of Aegle marmelos. Journal of Ethnopharmacology 1997; 57(1): 29-34. 6. Upadhya S, Shanbhag KK, Suneetha G, Balachandra Naidu M, Upadhya S. A study of hypoglycemic and antioxidant activity of Aegle marmelos in alloxan Induced diabetic rats. Indian Journal of Physiology & Pharmacology 2004; 48 (4): 476–80. 7. Narender T, Shweta S, Tiwari P, Papi Reddy K, Khaliq T, Antihyperglycemic and antidyslipidemic agent from Aegle marmelos. Bioorganic & Medicinal Chemistry Letters 2007; 17:1808–181. 8. Kesari AN, Gupta RK, Singh SK, Diwakar S, Watal G, Hypoglycemic and antihyperglycemic activity of Aegle marmelos seed extract in normal and diabetic rats. Journal of Ethnopharmacology 2006; 107(3): 374-79. 9. Kamalakkanan N, Prince PS, Antihyperlipidaemic effect of Aegle marmelos fruit extract in Streptozotocin-induced diabetes in rats. J. Sci. Food Agric 2005; 85: 569. 10. Goel RK, Maiti RN, Manickam M, Ray AB, Antiulcer activity of naturally occurring pyrano cumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa. Indian J Exp Biol 1997; 35: 1080-83. 6052 CONCLUSION This review gives somewhat evident that different parts of Aegle marmelos possess numerous phytoconstituents which expose its therapeutic significance of plant. A number of therapeutic investigation was carried out by different investigator on Aegle marmelos plant. But, most of the compounds have not properly been evaluated for the exploration of new lead molecule. In this view, natural plant more research can be done to investigate unexplored mechanism of action as well as to prove efficacy of medicinal value of plant in other therapeutic uses. ISSN NO: 2231-6876 11. Karakaya S, Bioavailability of phenolic compounds. Crit. Rev. Food Sci. Nutr 2004; 44: 453. 12. 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Kalyani publishers India 1997; 1: 1-160 Page Submit your next manuscript to IAJPR and take advantage of: • Access Online first • Double blind peer review policy • No space constraints • Rapid publication • International recognition Submit your manuscript at: [email protected] 6054 54878478451001763 www.iajpr.com