Antidiabetic and Anti-oxidant Activity of Aegle marmelos Extract in Streptozotocin-Induced Diabetic Rats

The aqueous extract of Aegle marmelos Correa. fruits (AMFEt) was studied in normal and streptozotocin (STZ) diabetic rats and anti-lipid peroxidative activity was studied in hepatic and renal tissues in diabetic rats. Oral administration of AMFEt for 30 days (twice a day) prevented significantly the STZ-induced hyperglycaemia and hypoinsulinemia. The extract also produced a significant decrease in peroxidation products, viz., thiobarbituric acid reactive substances and hydroperoxides in diabetic rats. The activity of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase was found to be increased in the hepatic and renal tissues of diabetic animals treated with AMFEt. AMFEt, at a dose of 250?mg/kg, was more effective than glibenclamide and reversed all the values to near normal status. Thus, AMFEt exhibits antidiabetic and anti-oxidative activity in STZ-diabetic 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.     

Antiproliferative and antioxidant activity of Aegle marmelos (Linn.) leaves in Dalton's Lymphoma Ascites transplanted mice

Objective:

The present investigation was performed to evaluate the antiproliferative and antioxidant activity of Aegle marmelos leaves in Dalton''s Lymphoma Ascites (DLA)-bearing mice.

Materials and Methods:

The DLA cells maintained in vivo in Swiss albino mice were used for developing ascitic tumor in mice by intraperitoneal transplantation. The standardized 50% ethanolic extract of A. marmelos leaves (AMEE) was administered intraperitoneally in dose levels 200 and 400 mg/kg, after 24 hours of tumor inoculation in mice for two weeks.

Results:

The AMEE treatment significantly prevented (P<0.001) the increase in body weight due to tumor cell growth and increased the mean survival time of the tumor-bearing mice as compared to the untreated DLA control mice. The treatment of DLA-bearing mice brought down the Alanine Aminotransferase (ALAT), Aspartate Aminotransferase (ASAT), and alkaline phosphatase to normal levels. The extract decreased the levels of hepatic lipid peroxidation and increased the levels of hepatic antioxidants Glutathione, Superoxide Dismutase (SOD), and catalase. All the changes observed with AMEE treatment were dose dependent.

Conclusion:

The hydroalcoholic extract of A. marmelos exhibits strong antitumor and antioxidant activities in DLA-bearing mice.KEY WORDS: Aegle marmelos, antioxidant activity, antiproliferative activity, Dalton''s Lymphoma Ascites     

Investigation on the gastroprotective and antidiarrhoeal properties of Aegle marmelos unripe fruit extract

The Study was designed to verify the gastroprotective and antidiarrhoeal effects of unripe fruit extract of Aegle marmelos Corr. The gastroprotective function of this extract was evaluated in rats against gastric mucosal damage induced by hypothermic restraint stress, absolute ethanol, and indomethacin, whereas the antidiarrhoeal activity was investigated by studying the influence on gastrointestinal transit as measured by a charcoal marker and on castor oil-induced accumulation of intestinal fluid in mice and also on contractile responses evoked by acetylcholine, histamine, serotonin, and barium chloride in isolated guinea-pig ileum, the results demonstrated that pretreatment of animals with unripe fruit extract (50 and 100 mg/kg, i.p.) produces a significant inhibition of gastric lesion induced by ethanol but not those induced by restraint stress or indomethacin and suggest a probable involvement of a prostaglandin-independent mechanism of gastroprotection. At similar doses, both the intestinal transit as well as the accumulation of intestinal fluids induced by castor oil in mice were significantly inhibited by raw fruit extract. Furthermore, the extract antagonized the contractile responses evoked by different agonists on guinea-pig ileum in vitro and its inhibitory potential for the drugs are in the order of acetylcholine > histamine > serotonin > barium chloride. Taken together, these results point out a possible antidiarrhoeal effect of unripe fruit extract of A. marmelos Corr., since inhibition of intestinal motility and secretion can control clinical diarrhoea.     

Evaluation of the anti-inflammatory activity of Aegle marmelos (Bilwa) root

Aims and objectives:

The purpose of this study was to evaluate and compare the anti-inflammatory activity of the aqueous root bark extract of Aegle marmelos (Bilwa) in experimental acute and chronic inflammatory animal models.

Materials and Methods:

Aqueous extract of root bark of Bilwa was prepared and tested for anti-inflammatory activity in albino rats weighing 150-280 grams. The animals were randomly divided into 3 groups of 6 each; one group served as control and other two groups received indomethacin and Bilwa orally 1 hour prior to experimentation. The in vivo anti-inflammatory activity was studied using the acute (Carrageenan induced paw edema) and chronic (Cotton pellet induced granuloma) animal models. Anti-inflammatory activity was expressed as Percent inhibition (PI). Statistical analysis was performed using One-way analysis of variance (ANOVA) followed by Scheffe''s post hoc test. P < 0.05 was considered statistically significant.

Results:

The PI with indomethacin and Bilwa in carrageenan induced paw edema were 52.7% and 46% and in cotton pellet induced granuloma were 24.7% and 9.2% respectively. Indomethacin showed highly significant anti-inflammatory activity in both the models. However, Bilwa showed highly significant activity in acute model and but a trend of anti-inflammatory activity in chronic model studied.

Conclusions:

As Bilwa showed significant anti-inflammatory activity in the models studied, it can be a promising anti-inflammatory agent.     

Immunomodulatory activity of methanolic fruit extract of Aegle marmelos in experimental animals

Aim

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.

Methods

Cellular immunity was carried out by neutrophil adhesion test and carbon clearance assay, whereas, humoral immunity was analyzed by mice lethality test and indirect haemagglutination assay. FEAM dose was selected by Stair case method (up and down) and administered at 100 and 500 mg/kg orally. The Ocimum sanctum (OSE, 100 mg/kg, p.o) was used as standard.

Results

FEAM at 100 and 500 mg/kg produced significant increases in adhesion of neutrophils and an increase in phagocytic index in carbon clearance 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 titre 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.

Conclusion

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).     

Antimicrobial activity and phytochemical screening of serial extracts from leaves of Aegle marmelos (Linn.)

The in vitro antimicrobial activity of serial petroleum ether, chloroform and methanol extracts from leaves of Aegle mawmelos were investigated against bacterial and fungal species. All the extracts exhibited broad spectrum antimicrobial activity with zones of inhibition ranging from 10 to 22 mm against bacteria: Staphylococcus aureus, beta Streptococcus haemolyticus group A, Proteus mimrabilis, Klebsiella pneumoniae, Pseudomonas aenrginosa, Escherichia coli, Salmonella typhi, fungi: Candida albicans, Candida tropicalis and Aspergillusflavus. The minimal inhibitory concentrations (MIC) and the minimal microbicidal concentrations (MMC) of the extracts ranged from 1.25 to 10 mg/mL and 2.5 to 20 mg/mL respectively. Assessment of antibacterial efficacy of different extract revealed that Staphylococcus aureus, beta Streptococcus haemolyticus group A, Pseudomonas aeruginosa and Escherichia coli showed high susceptibility to petroleum ether extract. Proteus mimrabilis, Klebsiella pneumoniae showed high susceptibility to chloroform extract and Salmonella typhi showed high susceptibility to methanol extract. Petroleum ether extract exhibited the highest antifungal efficacy against all tested fungal species. Phytochemical screening revealed the presence of phenols, sterols in petroleum ether and chloroform extracts, whereas tannins, flavonoids, coumarins, saponins and triterpenoids in methanol extract. The ability of the leaf extracts of Aegle manmelos to inhibit growth of bacteria and fungi is an indication of its broad spectrum antimicrobial activity which could be a potential source for development of novel bioactive antimicrobial agents.     

Immunomodulatory Potential of Methanol Extract of Aegle marmelos in Animals

The aim of the current research was to evaluate the immunomodulatory potential of methanol extract of Aegle marmelos in an experimental animal model of cellular and humoral immunity. Administration of methanol extract of Aegle marmelos (500 and 1000 mg/kg, p.o.) and Ocimum sanctum (100 mg/kg, p.o.), produced significant increase in adhesion of neutrophils and an increase in phagocytic index in carbon clearance assay. Both doses of Aegle marmelos prevented the mortality induced by bovine Pasteurella multocida in mice. Moreover, all treated groups demonstrated significant elevation in circulating antibody titre in the indirect haemagglunation test. From the above results, it can be concluded that methanol extract of Aegle marmelos possess immunomodulatory potential by stimulating cellular and humoral immune mechanisms. However, low dose of methanol extract of Aegle marmelos was more effective for augmenting cellular immunity, whereas, high dose was more inclined towards humoral immunity.     

Protective Effect of Aegle marmelos Fruit in Gastrointestinal Dysfunction in rats

The effect of the ethanol extract of the unriped fruits of Aegle marmelos Correa was assessed on experimentally induced diarrhoea and gastric ulceration in rats. The extract (50, 100 and 200?mg/kg, p.o.) exhibited a dose-dependent decrease in the intestinal propulsion from 61.79–39.32% which is equivalent to 38.21–60.68% intestinal propulsion inhibition (control 58.3 ± 3.4 inhibition, P < 0.5 to P < 0.001) and caused a dose-dependent decrease in the total number of faecal matter in castor oil-induced diarrhoea (control 70, reduced to 51 and 42 at 100 and 200?mg/kg extract, p.o.). Further, yohimbine, a α₂ adrenoreceptor blocker, attenuated the antidiarrhoeal effect of the extract in a dose of 200?mg/kg to 17.14%, and diphenoxylate by 74.28%. The extract also reduced the ulcer index induced by ethanol (control 18.7 ± 4.4, 34.22–72.73% protection), aspirin (control 22.6 ± 3.4, 36.73–81.42% protection) and cold restraint stress (control 23.8 ± 3.2, 56.72% and 81.51% protection). Further study on tissue lipid peroxidation was significantly increased (P < 0.001) as evidenced by accumulation of malondialdehyde in cold restraint stress ulcers. Administration of A. marmelos (100 and 200?mg/kg), cimetidine 50?mg/kg and reduced glutathione (150?mg/kg) prior to cold restraint stress causes significant decrease in ulcer index and lipid peroxidation (P < 0.01 to P < 0.001). The result showed that A. marmelos had significant antidiarrhoeal and ulcer protective activity by scavenging the reactive oxygen species on the cold restraint stress-induced gastric damage.     

Effect of hydroalcoholic extract of Aegle marmelos fruit on radical scavenging activity and exercise-endurance capacity in mice

Context: Aegle marmelos L. Corr (Rutaceae) is an important Indian Ayurvedic medicinal plant used for the treatment of various ailments. However, little information is available on the anti-fatigue properties of its fruit.

Objective: Evaluation of the physical endurance and exercise-induced oxidative stress modulating properties of A. marmelos fruit in mice.

Material and methods: Radical scavenging activity of the fruit hydroalcoholic extract was evaluated using in vitro systems. The extract was further evaluated for its endurance-enhancing properties at three oral doses (100, 200 and 400?mg/kg?b.wt) in BALB/c mice for 21?d using a swimming test.

Results and discussion: The extract exhibited significant scavenging activity against DPPH (IC₅₀, 351?±?37?µg/ml) and ABTS radicals (IC₅₀, 228?±?25?µg/ml), respectively, with the polyphenol content of 95?µg/mg extract. It also inhibited AAPH radical-induced oxidation of biomolecules such as BSA protein (63%), plasmid DNA (81%) and lipids (80.5%). Administration of extract resulted in an increase in the duration of swimming time to exhaustion by 23.4 and 47.5% for medium and higher doses, respectively. The extract significantly normalized the fatigue-related biochemical parameters and also down-regulated the swim stress-induced over-expression of heat shock protein-70 and up-regulated the skeletal muscle metabolic regulators (GLUT-4 and AMPK1-α) by 2- and 3-fold, respectively, at the higher dose in muscle tissues.

Conclusion: Our study demonstrates the anti-fatigue properties of A. marmelos fruit, most probably manifested by delaying the accumulation of serum lactic acid, increasing the fat utilization and up-regulating the skeletal muscle metabolic regulators.     

Inhibition of CYP3A4 and CYP1A2 by Aegle marmelos and its constituents

1.?Aegle marmelos (bael) is a popular tree in India and other Southeast Asian countries. The fruit is usually consumed as dried, fresh or juice, and is reported to have a high nutritional value and many perceived health benefits. Despite its edible nature and therapeutic properties, no studies are reported regarding its effects on major drug metabolizing enzymes.

2.?This study was aimed to evaluate the inhibitory potential of methanolic extract of A. marmelos fruit and its constituents (three furanocoumarins, namely marmelosin, marmesinin and 8-hydroxypsoralen, and 1 alkaloid, aegeline) towards major Cytochrome P450 enzymes (CYP3A4, 2D6, 1A2, 2C9 and 2C19) using human liver microsomes and recombinant CYPs.

3.?The methanolic extract and marmelosin was found to be competitive and time-dependant inhibitor of CYP3A4. While reversible and non-competitive inhibition was observed for CYP1A2. Time-dependent inhibition of CYP3A4 was not affected by the addition of reduced glutathione. Marmesinin showed moderate inhibition of CYP3A4 and 1A2, while aegeline was a very weak inhibitor of CYP3A4 and showed no inhibition for CYP1A2 isoform. No significant inhibition of recombinant CYP2D6, 2C9, and 2C19 was seen with the extract or its constituents.

4.?This is the first report of CYP3A4 and CYP1A2 inhibition by A. marmelos extract and one of its furanocoumarins, marmelosin. Further studies are warranted to determine if acute or prolonged use of bael fruit could affect the pharmacokinetics of drugs that are substrates of CYP3A4 or CYP1A2.     

Anxiolytic and antidepressant activities of methanol extract of Aegle marmelos leaves in mice

The objective of the present study was to evaluate the anxiolytic and antidepressant activities of methanol extract of Aegle marmelos (AM) 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 (a) time spent on (b) number of entries into (c) number of stretch attend postures (d) number of head dips in arms of elevated plus maze and on duration of immobility in tail suspension test. Effects of pretreatment with prazosin (0.062 mg/kg, po), haloperidol (0.1 mg/kg, po) and baclofen (10 mg/kg, po) were also studied on AM induced decrease in duration of immobility. Effects of AM (75, 150 and 300 mg/kg po) were observed on locomotor activity using photoactometer. Results showed that AM 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 AM. Combination of AM (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. Antidepressant activity of AM (150 mg/kg, po) was significantly (P<0.05) decreased by prazosin, haloperidol and baclofen. Methanol extract showed insignificant (P>0.05) effect on locomotor activity of mice. It is concluded that AM possess potential anxiolytic and antidepressant activities and it enhances the anxiolytic and antidepressant activities of imipramine and fluoxetine.     

Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease

Objective:

The present study was designed to evaluate the effect of Aegle marmelos unripe fruit extract (AMFE) on inflammatory bowel disease (IBD) in Wistar albino rats.

Materials and Methods:

Effect of AMFE was studied on acetic acid induced ulcerative colitis (1 ml of 4% acetic acid solution, transrectal) and indomethacin-induced enterocolitis (10 mg/kg, single dose, p.o) in Wistar albino rats. The extract was administered orally at different dose of 150, 200 and 250 mg/kg body weight. Disease pathogenesis was assessed by measuring disease activity index (DAI), macroscopic score, microscopic score, mesenteric mast cell protection, superoxide dismutase (SOD), and malonaldehyde (MDA) levels in the above two models.

Results:

The results showed a dose dependent decrease in intestinal inflammation following treatment with AMFE. Significant protection in mast cell degranulation was observed in acetic acid and indomethacin-induced IBD models. Treatment with AMFE significantly decreased the MDA levels and increased SOD activity.

Conclusion:

In our study, AMFE produced anti-inflammatory, antioxidant, and mast cell stabilizing effects demonstrating protective effect in inflammatory bowel disease.KEY WORDS: Aegle marmelos (bael), aqueous extract, inflammatory bowel disease     

Pharmacognostic standardisation and antiproliferative activity of Aegle marmelos (L.) Correa leaves in various human cancer cell lines

Therapeutic management of cancer is a great clinical challenge and alternative medicines are being extensively explored to have integrated approach to cure cancer. Aegle marmelos (L.) Correa (Rutaceae) is known for its hypoglycaemic, radioprotective, antidiarrhoeal and many other pharmacological activities. The present study is designed to carryout pharmacognostic standardisation and evaluation of antiproliferative activity of the leaf extracts Aegle marmelos (L.) Correa (Rutaceae) and the chromatographic fractions of the most active extract. Hexane, petroleum ether, chloroform and ethanol extracts of the shade dried leaves were prepared by soxhelation and antiproliferative activity was assessed using human cancer cell lines of lung (A-549), colon (CoLo-05), ovary (IGR-OV-1), prostrate (PC3), leukaemia (THP-1) and breast (MCF-7) cancer. Bioactivity-derived fractionation was carried out for most active extract by column chromatography. The phytochemical studies indicated alkaloids, anthraquinones, terpenoids in the alcohol, chloroform extracts and tannins, terpenoids, reducing sugars in the petroleum ether and hexane extracts. Ethanol extract showed maximum inhibition in colon and breast carcinoma cell lines at a dose of 100 μg/ml. Column chromatography of the ethanol extract yielded five fractions. Out of this, fractions 2, 4 and 5 showed significant inhibition in leukaemia cell line with IC₅₀ of 12.5, 86.2 and >100 μg/ml for fractions 2, 4 and 5, respectively. High-performance thin layer chromatography of the fraction 2 revealed imperatorin as one of the major phytoconstituents. Among the different extracts investigated, ethanol extract exhibited significant antiproliferative activity and its fraction 2 containing furanocoumarin imperatorin showed antiproliferative activity against leukaemia cell line with IC₅₀ of 12.5 μg/ml.     

Involvement of opioid and monoaminergic pain pathways in Aegle marmelos induced analgesia in mice

Objective:

To study analgesic activity and to evaluate the involvement of opioid and monoamines in the antinociceptive activity of methanol extract of leaves of Aegle marmelos.

Materials and Methods:

Analgesic activity of methanol extract (ME) of A. marmelos alone (75,150 and 300mg/kg orally) and in combination with morphine or venlafaxine (subanalgesic) were studied using tail flick test and acetic acid-induced writhing in mice. The effect of pre-treatment with opioid antagonist naltrexone 1mg/kg was also studied on antinociception induced due to ME.

Result:

ME produced a dose-dependent significant antinociceptive activity in the tail flick test and acetic acid-induced writhing in mice. (P<0.05) Administration of subanalgesic dose of ME with morphine or venlafaxine also resulted in significant (P<0.05) antinociceptive activity in both the pain models. Pre-treatment with naltrexone inhibited analgesic activity induced by ME alone and combination with morphine or venlafaxine.

Conclusion:

A.marmelos in induced antinociception is mediated through both opioid and monoaminergic pain pathways, suggest its possible use in chronic pain.KEY WORDS: Aegle marmelos, analgesia, monoamines, opioid, tail flick latency     

Antidiabetic and antioxidant activity of Swietenia mahagoni in streptozotocin-induced diabetic rats

Context: Swietenia mahagoni L. Jacq. (Meliaceae) is a medium to large evergreen tree native to Southern Florida, Cuba, The Bahamas, Hispaniola, and Jamaica.

Objective: To evaluate the antidiabetic and antioxidant potential of S. mahagoni bark.

Materials and methods: In the present study, the antidiabetic activity of the methanol extract of S. mahagoni (MESM) bark in streptozotocin (STZ; 65?mg/kg body weight)-induced diabetic rats was evaluated. Glibenclamide (0.5?mg/kg; orally) was taken as the reference drug. The blood glucose levels and body weights were measured every 5th day over a period of 15 days. Antioxidant effects were assayed in diabetic rats by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and catalase (CAT) levels.

Results and discussion: Oral administration of MESM at the doses of 25 and 50?mg/kg b.w. resulted in a significant (p?<?0.001) reduction in blood glucose levels in diabetic rats. Body weights were significantly (p?<?0.001) reduced in STZ-induced diabetic rats when compared to normal rats, while the extract significantly restored body weight. The present study was further undertaken to evaluate the antioxidant activity of MESM in STZ-induced diabetic rats. Decreased levels of TBARS and increased levels of GSH and CAT activity indicated a reduction in free radical formation in tissues such as the liver and kidney of diabetic rats.

Conclusion: These findings showed the significant hypoglycemic and antioxidant activity of the extract (MESM) in diabetic rats.     

Analgesic and antioxidant activity of mangiferin and its derivatives: the structure activity relationship

Mangiferin, 2-beta-D-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one, obtained directly from methanolic extracts of Bombax ceiba leaves in substantial amounts demonstrated strong antioxidant activity (EC(50) 5.8+/-0.96 mug/ml or 13.74 muM) using DPPH assay comparable to rutin, commonly used as antioxidant for medical purposes. The acetyl and cinnamoyl derivatives were found to be less active than mangiferin whereas, methyl and 3,6,7-trimethylether tetraacetate derivatives were inactive implying that for antioxidant activity, free hydroxyl groups and catechol moiety are essential. Moreover, mangiferin showed hepatoprotective activity against carbon tetrachloride induced liver injury further supporting the free radical scavenging property in the in vivo system. Additionally, plant extracts and mangiferin failed to exhibit acute anti-inflammatory activity whereas, it displayed significant analgesic effect in acetic acid-induced writhing and hot plate tests in mice. Using naloxone, it was revealed that plant extracts induced analgesia was independent of opioid receptor, whereas, mangiferin demonstrated significant interaction with it at peripheral site with a slight contribution at the neuronal level.     

Effect of Aegle marmelos on DEN initiated and 2-AAF promoted hepatocarcinogenesis: a chemopreventive study

In this study, we examined the inhibitory effects of Aegle marmelos methanolic extract on diethylnitrosamine (DEN) initiated and 2-acetyl aminofluorene (2-AAF) promoted liver carcinogenesis in male Wistar rats. Interestingly, it was found that A. marmelos (25 and 50?mg/kg body weight) resulted in a marked reduction of the incidence of liver tumors, which was further confirmed with histopathology. Furthermore to understand the underlying mechanisms of chemoprevention potential of A. marmelos, we evaluated the levels of hepatic antioxidant defence enzymes, ornithine decarboxylase (ODC) activity and hepatic DNA synthesis as a marker for tumor promotion since a direct correlation between these marker parameters and carcinogenicity have been well documented. Treatment of male Wistar rats for five consecutive days with 2-AAF induced significant hepatic toxicity, oxidative stress and hyper-proliferation. Pretreatment of A. marmelos extract (25 and 50?mg/kg body weight) prevented oxidative stress and toxicity by restoring the levels of antioxidant enzymes at both the doses. The promotion parameters (ODC activity and DNA synthesis) induced by 2-AAF administration in diet with partial hepatectomy (PH) were also significantly suppressed dose-dependently by A. marmelos. Therefore, we can conclude that ultimately the protection against liver carcinogenesis by A. marmelos methanolic extract might be mediated by multiple actions, which include restoration of cellular antioxidant enzymes, detoxifying enzymes, ODC activity and DNA synthesis.