Phytochemical profile and pharmacological activity of Aegle marmelos Linn / 中西医结合学报

Aegle marmelos Linn. (Rutaceae), commonly known as "bael" in Nepal and India, is a valuable medicinal plant and is considered sacred by the Hindus. It is used to cure several diseases in the Indian traditional medicine system of Ayurveda and has had similar uses among many ethnic communities residing in Indian subcontinent for over 5000 years. Its leaves, bark, stem, fruits and seeds have been used for various medicinal purposes. Bael fruits are especially effective in the treatment of chronic diarrhea, dysentery and peptic ulcers, while they are also useful as a laxative and cure for respiratory infections. Scientific studies have validated many of the ethnomedicinal uses of A. marmelos, which include antibacterial, antiviral, antidiarrheal, gastroprotective, anti-ulcerative colitis, hepatoprotective, antidiabetic, cardioprotective and radioprotective effects. Recently, this plant has also received attention as an anticancer agent for the treatment of various types of cancers. Thus, this review focuses on scientific evidence verifying the important pharmacological activity such as antioxidant, antidiabetic, antimicrobial, hepatoprotective, cardioprotective and anticancer activity of A. marmelos.

Aggravation of cyclophosphamide-induced reproductive toxicity in mice by aqueous extract of Aegle marmelos (L. )

ABSTRACT Aegle marmelos (L.) (Rutaceae) commonly known as bael is an important medicinal fruit tree. The present study focused on the effects of aqueous extract of Aegle marmelos (AEAM) on the testis and sperm characteristics induced by cyclophosphamide (CPA) in mice. Thirty six adult Parke's strain mice were divided into six groups: group I given only distilled water (control); group II administered with AEAM alone once in a week for five weeks; group III administered with CPA (200 mg/kg b.w., intraperitoneally) once in a week for five weeks and group IV-VI CPA along with AEAM (400, 500 and 600 mg/kg b.w., orally). CPA was found to reduce gonadosomatic index (GSI), sperm counts, motility, viability, antioxidant activities and induced histopathological changes of testis. In the group administered AEAM with CPA an exacerbation of sperm count, motility and viability of the cauda epididymis, GSI, antioxidant activities and architecture of testis was observed. The results suggest that the administration of AEAM may aggravate CPA-induced reproductive toxicity. It may be helpful in preparation of natural male contraceptives.

Bioprospecting Endophytic Fungi and Their Metabolites from Medicinal Tree Aegle marmelos in Western Ghats, India

The increasing emergence of lead drugs for the resistance produced by the pathogenic strains and arrival of new diseases have initiated the need for searching novel metabolites with best anticancer and antimicrobial properties than the existing one. With this view, the investigation was conducted for the isolation, identification, and biological evaluation of potential endophytic fungi of Aegle marmelos, a medicinal tree used for more than three decades, for curing various disorders. A total of 169 endophytic fungal strains obtained from sampling and among those 67 were pigmented strains. Upon antagonistic screening, five endophytic fungal strains exhibited antagonistic potentiality by inhibiting the pathogens. These five potent strains were characterized at molecular level by sequencing the amplified internal transcribed spacer (ITS) 1 and ITS 4 regions of rDNA and they were grouped under order Pleosporales, Eurotiales, and Capnodiales. The metabolites from the respective strains were produced in fungal culturing media and extracted using polar solvents. Further, the extracts of five endophytes manifested antimicrobial activity against tested clinical pathogens and Alternaria alternata (FC39BY), Al. citrimacularis (FC8ABr), and Curvularia australiensis (FC2AP) exhibited significant antimicrobial profile against 9 of 12 tested pathogens, showing broad spectrum activity. The antioxidant levels of all the five endophytes revealed the highest activity at least concentrations, and major activity was unveiled by the members of order Pleosporales FC2AP and FC8ABr. This research explains the value of endophytic fungal extracts and its significance of antimicrobial and antioxidant properties.

Effect of Aegle marmelos (L.) Correa on alloxan induced early stage diabetic nephropathy in rats.

Diabetic nephropathy (DN) has a complex pathogenesis and poor prognosis due to the lack of therapeutic interventions. The present study investigates the effect of A. marmelos leaf extract (AME) on early alloxan induced DN. The treatment with AME was found to significantly decrease the fasting blood sugar, total cholesterol, blood urea, creatinine and renal TBARS and increased the levels of renal reduced glutathione and catalase significantly as compared to the diabetic control group. The maximum dose-dependent protection was observed at a dose of 200 mg kg-1. Histological examination revealed marked reversal of the morphological derangements with AME treatment as indicated by a decrease in glomerular expansion, tubular dilatation and inflammatory cells. The present results conclude that AME treatment has a significant ameliorative effect on early changes induced in the kidneys by alloxan and improves the outcome of DN.

Healing effects of Aegle marmelos (L.) Correa fruit extract on experimental colitis.

Graded doses of 50% ethanolic extract of dried fruit pulp of Aegle marmelos (AME) (100, 200 and 400 mg/kg) daily for 14 days in acetic acid (AA)-induced colitis in rats showed 200 mg/kg of AME as an optimal effective dose against AA-induced colonic damage score and weight. This dose (200 mg/kg; po) was further studied in AA-induced colitis for its effects on various physical (mucous/blood in stool, food and water intake and body weight changes), histology, antibacterial activity and biochemical parameters like free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and myeloperoxidase (acute-inflammatory marker) activities in rat colonic tissue. AME decreased colonic mucosal damage and inflammation (macroscopic and microscopic), mucous/bloody diarrhea, fecal frequency and increased body weight affected in AA-induced colitis. AME showed significant antibacterial activity and enhanced the antioxidants but decreased free radicals and myeloperoxidase activities thereby decreasing tissue damage and inflammation and thus, affording ulcer healing. The above effects of A. marmelos authenticated its use in indigenous system of Medicine.

Antifungal activities of some plant extracts against Fusarium solani and their molecular characterization

The present investigation was carried of the antifungal properties of leaf extract of Aegle marmelos [L.], Trianthema decandra Linn., Sphaeranthus indicus Roxb., Borreria hispida and Leucas aspera against ten clinical isolates of Fusarium solani strains from Aravind Eye Hospital, Coimbatore. The antifungal assay was determined by disc diffusion method by using the solvents such as ethanol, benzene, dimethyl formaldehyde and distilled water used, the leaves of Aegle marmelos Correa, Trianthema decandra and borreria hispida had been extracted with DMF instead of benzene. The results revealed that the ethanolic extract having significant inhibitory activity when compared to other solvent. There was no activity found in aqueous extracts against all strains. Fusarium solani [4th strain] was not inhibited by solvent extracts of all plant leaves. Based on the high inhibitory activity, the six strains were selected and the DNA were isolated from that Fusarium solani

Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction of the guinea pig-isolated trachea

Marmin or 7-[6', 7'-dihydroxygeranyl-oxy] coumarin is a compound isolated from Aegle marmelos Correa. In the study, we examined the effects of marmin on the contraction of guinea pig-isolated trachea stimulated by several inducers, namely histamine, metacholine, compound 48/80. We also evaluated its action against contraction induced by extracellular or intracellular calcium ion. The possibility of marmin to potentiate the

elaxation effect of isoprenaline was also studied. Marmin added in the organ bath at 10 min prior to the agonist inhibited the contraction elicited by histamine and metacholine in a concentration-dependent manner. Moreover, marmin antagonized the histamine-induced contraction in competitive manner. Marmin mildly potentiated the relaxation effect of isoprenaline. In the study, marmin abrogated the contraction of tracheal smooth muscle induced by compound 48/80, an inducer of histamine release. Besides, marmin successfully inhibited CaCl[2-]-induced contraction in Ca[2+] -free Krebs solution. Marmin also inhibited two phases of contraction which were consecutively induced by metacholine and CaCl[2] in Ca[2+]-free Krebs solution. Based on the results we concluded that marmin could inhibit contraction of the guinea-pig tracheal smooth muscle, especially by interfering histamine receptor, inhibiting the histamine release from mast, inhibiting intracellular Ca[2+] release from the intracellular store and the Ca[2+] influx through voltage-dependent Ca[2+] channels

comparative evaluation of medicinal plants for their hypoglycaemic activity in streptozotocin-induced diabetic rats

In the present study, the hypoglycaemic effect of alcoholic extracts of Momordica charantia, Aegle marmelos, and Eugenia jambolana was studied in Streptozotocin [STZ]- induced diabetes. Rats were made diabetic using intraperitoneal injection of STZ [30 mg/kg] in citrate buffer. On confirmation of diabetes after 48 hrs of injection, alcoholic extract of medicinal plant [250 or 500 kg] or glibenclamide [300 micro g/kg] administrated orally to rats for 30 days. These three plants produced dose and duration dependent hypglycaemia very similar to that of glibenclamide. At the end of one month, serum glucose levels of STZ diabetic rats with daily doses of 500 mg/kg of any one of the alcoholic extract were 'more or less' comparable to that of normal rats. The anti-diabetic effect of these plants might be due to enhanced insulin secretion from the viable beta-cells of islets of Langerhans as evidenced by presence of more viable beta-cells and less necrotic changes in the pancreas of diabetic rats as compared to that of control diabetic rats. Thus, these plants appear to be better alternative for the diabetic patients who are prone to develop side effects with the regular use of synthetic hypoglycaemic drugs as these plants are devoid of any untoward/toxic effects

Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos (Linn.) in hyperlipidaemic models of Wistar albino rats.

Lipid lowering effect of 50% ethanolic extract of the leaves of A. marmelos (Linn.) was evaluated in triton and diet induced hyperlipidaemic models of Wistar albino rats. The extract at 125 and 250 mg/kg dose levels inhibited the elevation in serum cholesterol and triglycerides levels on Triton WR 1339 administration in rats. The extract at the same dose levels significantly attenuated the elevated serum total cholesterol and triglycerides with an increase in the high-density lipoprotein cholesterol in high-fat diet- induced hyperlipidaemic rats. The standard drugs atorvastatin in the former and gemfibrozil in the latter studies showed slightly better effects.

Xenobiotic metabolising enzymes in DLA induced Balb/c mice and on treatment with protein fractions of Cynodon dactylon and Aegle marmelos

The investigation on xenobiotic metabolising enzymes have been carried out in mice liver. In the present study, in vivo studies were carried out using BaIb/c mice. DLA cells were transplanted intraperitoneally and ED[50] dose of protein fractions of Cynodon dactylon and Aegle marmelos were injected intraperitoneally once a day during the course of the study. The levels of xenobiotic metabolizing enzymes phase I [Cytochrome b[5] and P450] and phase II [Glutathione S-Transferase] were found to be increased and decreased in DLA induced mice. Administration of protein fractions significantly reversed the level of enzymes both in the presence and absence of DLA cells. These results indicated the protective role of protein fractions

In vitro effect of four herbal plants on the motility of Brugia malayi microfilariae.

BACKGROUND & OBJECTIVE: Disease burden due to lymphatic filariasis is disproportionately high despite mass drug administration with conventional drugs. Usage of herbal drugs in traditional medicine is quite well known but largely empirical. Hence the present study was designed to screen the in vitro antifilarial effect of four herbal plants on Brugia malayi. METHODS: Motility of microfilariae of B. malayi after incubation for 48 h with aqueous/methanol extracts of Vitex negundo L. (roots), Butea monosperma L. (roots and leaves), Ricinus communis L. (leaves), and Aegle marmelos Corr. (leaves) was explored in the concentration range of 20 to 100 ng/ml for possible antifilarial effect by comparing with suitable solvent control. RESULTS: Butea monosperma leaves and roots, Vitex negundo root and Aegle marmelo leaves showed significant inhibition of motility of microfilariae as compared to controls whereas inhibitory activity demonstrated by Ricinus communis L. leaves was not significant. Antifilarial effects imparted by all these extracts were found to be a function of their relative concentrations. Inhibitory concentrations (IC(50)) for the plant extracts with significant antifilarial activity against Brugia malayi microfilariae in in vitro system have been derived to be 82, 83 and 70 ng/ml for Vitex negundo L., Butea monosperma L. and Aegle marmelos Corr. respectively. INTERPRETATION & CONCLUSION: The present study recorded significant antifilarial effect of all plant extracts studied except for Ricinus communis L. leaves and contributes to the development of database for novel drug candidates for human lymphatic filariasis.

Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle marmelos and their phytochemical analysis.

In the present study, methanolic extracts of roots of Vitex negundo L. and extracts of leaves of Vitex negundo L., Ricinus communis L. and Aegle marmelos Corr. were explored for possible antifilarial effect against Brugia malayi microfilariae. It was observed that among the herbal extracts, root extract of Vitex negundo L. and leaves extract of Aegle marmelos Corr. at 100 ng/ml concentration showed complete loss of motility of microfilariae after 48 hr of incubation. Thin layer chromatography of the extracts revealed the presence of alkaloids, saponin and flavonoids in the roots of Vitex negundo L. and coumarin in the leaves of Aegle marmelos Corr.

Antibacterial Screening of Aegle Marmelos; Lawsonia Inermis and Albizzia Libbeck

Three medicinal plant Aegle marmelos; Lawsonia inermis; Albizzia libbeck were extracted by soxhlet apparatus using petroleum ether; ethanol; chloroform and aqueous as solvent. Among those extract; the petroleum ether was considered as effective one. The extracts were subjected to preliminary phytochemical screening and the three plants with four extracts were tested against three Gram positive bacteria (B.cereus; B.subtilis; S. aureus) and three Gram negative bacteria (E.coli; P.vulgaris; and P.aeruginosa) by disc diffusion method. Maximum inhibition (3.8cm) was recorded in Lawsonia inermis. It also showed inhibitory action against all the six pathogen tested. The zone of inhibition of the extracts was compared with the standard antibiotics Streptomycin and Spectinomycin. The study suggests that the plant is promising the development of phytomedicine for antimicrobial properties

Safety evaluation of aqueous extracts from Aegle marmelos and Stevia rebaudiana on reproduction of female rats.

The purpose of this study was to evaluate the safety of a Thai medicinal plant, Aegle marmelos, and a non-caloric sweetener, Stevia rebaudiana, on the reproduction of female rats. Female rats were treated orally with aqueous extract of A. marmelos (6%) and S. rebaudiana at various concentrations (0, 0.2, 1, or 10%) for 60 days (1 ml/day) before mating. The control rats received only distilled water. At the end of the treatment period, treated females were mated with untreated males and the effects on reproduction were examined at day 14 of pregnancy. No notable abnormalities were observed in any of the pregnant rats. The number of corpus lutea, implanted and dead fetuses, as well as the sizes of the fetuses in the treated rats were not significantly different from those of the controls. Based on these results, it may be concluded that aqueous extracts of A. marmelos and S. rebaudiana at the concentrations used in this study do not alter the reproduction of female rats.

A study of hypoglycemic and antioxidant activity of Aegle marmelos in alloxan induced diabetic rats.

The present study was performed to evaluate the hypoglycemic and antioxidant effect of aqueous extract of Aegle marmelos leaves (AML) on diabetic rats. Male albino rats were randomly divided into three groups: Group I: Control; Group II: Diabetic rats; and Group III: Diabetic rats administered AML. Glucose, urea and glutathione-S-transferase (GST) in plasma, glutathione (GSH) and malondialdehyde (MDA) levels in erythrocytes were estimated in all the groups at the end of four weeks. There was a decrease in blood glucose at the end of four weeks in group III animals compared with group II, however it did not reach the control levels. There was an increase in erythrocyte GSH and a decrease in MDA in group III as compared to group II. The plasma GST levels were raised in diabetic rats when compared to controls. In the group III animals, there was a decrease in GST as compared to group II. Owing to hypoglycemic and antioxidant properties, AML may be useful in the long-term management of diabetes.

Antidiabetic activity of Aegle marmelos and its relationship with its antioxidant properties.

Oxidative stress induced by alloxan has been shown to damage pancreatic beta-cell and produce hyperglycemia in rats. Aegle marmelos leaf extract is being used in Ayurveda as a medicine for diabetes. The present study examined the action of Aegle marmelos against experimental diabetes as well as the antioxidant potential of the drug. A methanolic extract of Aegle marmelos was found to reduce blood sugar in alloxan diabetic rats. Reduction in blood sugar could be seen from 6th day after continuous administration of the extract and on 12th day sugar levels were found to be reduced by 54%. Oxidative stress produced by alloxan was found to be significantly lowered by the administration of Aegle marmelos extract. This was evident from a significant decrease in lipid peroxidation, conjugated diene and hydroperoxide levels in serum as well as in liver induced by alloxan. Catalase and glutathione peroxidase activity in blood and liver were found to be increased from 9th day onwards after drug administration. Superoxide dismutase and glutathione levels were found to be increased only on 12th day. These results indicate that Aegle marmelos extract effectively reduced the oxidative stress induced by alloxan and produced a reduction in blood sugar.

Effect of Aegle marmelos Correa. (Bael) fruit extract on tissue antioxidants in streptozotocin diabetic rats.

A study was undertaken to evaluate the anti-lipid peroxidative activity of an aqueous extract of A. marmelos fruits (AMFEt) in streptozotocin diabetic rats in heart and pancreas. Oral administration of AMFEt for 30 days (125 and 250 mg kg(-1) body weight twice daily) produced a significant decrease in the elevated levels of peroxidation products, viz. thiobarbituric acid reactive substances and hydroperoxides in the tissues of diabetic rats. The depressed activities of superoxide dismutase, catalase and glutathione peroxidase and lowered glutathione content in the heart and pancreas of diabetic rats were found to increase on treatment with AMFEt. AMFEt at a dose of 250 mg kg(-1) was more effective than glibenclamide (300 microg kg(-1)) and both reversed all the values significantly. Thus AMFEt exhibits anti-oxidative activity in streptozotocin diabetic rats.

In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses B1-B6.

The in-vitro antiviral activity of a series of compounds in samples extracted from various parts of the Indian holy tree, Bael (Aegle marmelos corr.) were evaluated for their efficacy against human coxsackieviruses B1-B6. The inhibitory concentrations (IC50) for leaves (L1 and L2) stem and stem bark (S1, S2, S3 and S4) fruit (F1 and F2micro) root and root bark (R1 and R2) and pure compound, the marmelide were 1000 microg/ml (for L1 and L2), 1000 microg/ml (for S1, S2, S3 and S4), 1000 microg/ml (for F1) and 500 microg/ml (for F2) 250 microg/ml (for R1) and 500 microg/ml (for R2) and 62.5 microg/ml for marmelide respectively by plaque inhibition assay at 96 hrs. On the other hand, the corresponding value for Ribavirin, a standard antiviral drug, was 2000 microg/ml for the same viruses at the same time period. These concentrations did not exhibit any toxicity to Vero cells, the host subtoxic concentrations were 5000 microg/ml for leaf and stem fractions 2000 microg/ml for fruit fractions 500 and 1000 microg/ml for root fractions 250 microg/ml for marmelide and 2000 microg/ml for Ribavirin. The cytotoxic concentrations were 8000 microg/ml for leaf and stem compounds 4000 mg/ml for fruit; 1000 microg/ml and 2000 microg/ml for root 500 microg/ml for marmelide and 4000 microg/ml for ribavirin at 96 hrs. These were also confirmed by trypan blue dye exclusion test and further passaging of cells. Additionally pretreatment of host cells, virus inactivation, yield reduction and effect of time of addition assays against coxsackievirus B3 suggested that marmelide was most effective as a virucidal agent besides interfering at early events of its replicative cycle like adsorption, penetration, at various steps in single cycle growth curve and effect of time of addition.