Search

Hepatocarcinogenesis is a multistep process involving different genetic alterations that ultimately lead to malignant transformation of the hepatocytes. Modern treatment of cancer includes chemotherapy, hormone therapy, radiotherapy and surgery but they are associated with several adverse effects such as alopecia, fatigue and general weakening of the body’s immune system due to bone marrow suppression. However, there is a continual need to look out for newer drugs to overcome the menace of cancer. In view of this we synthesized the new Coumarin-Cobalt complex derivatives. Structures of all the newly synthesized metal complexes are supported by Spectral data such as IR, NMR, and mass spectrometry. Coumarin-Cobalt complex of vanillin exhibited significant anti-cancer activity by in vivo anticancer activity (BrdU estimation). Immunohistochemical analysis has been done by BrdU and the synthesized compounds were screened for anti-oxidant activity and in vitro HepG2 cell lines. The IC50 values of the HepG2 cell lines as compared with that of standard Cisplatin and compounds IIIb, IIId, IIIe, IIIh and IIIj showed appreciable activity at a concentration less than 10 μG. Coumarin-Cobalt complex of vanillin exhibited significant anti-cancer activity. Anti-oxidant activity performed by Nitric oxide reducing ability, Superoxide dismutase and reducing activity:Compounds IIIc, IIIe and IIIg showed appreciable activity at 400μg/mL and 800 μg/mL screened by nitric oxide reducing ability, superoxide anion was effectively scavenged by compound IIIg at 400μg/mL and 800 μg/mL and reducing power of compounds IIIc and IIIj is comparable with standard ascorbic acid at concentrations 400μg/mL and 800 μg/mL.

A novel series of metal complexes of coumarin Schiff bases have been synthesized by reacting to coumarin Schiff bases with cobalt (II) nitrate and zinc chloride. The IR, 1H and NMR spectral data were obtained to characterize the structures of newly synthesized compounds. Newly synthesized compounds were evaluated for acute anti-inflammatory activity using carrageenan-induced rat paw edema and analgesic activity by acetic acid induced writhing method. In acute anti-inflammatory activity, the rat paw volume was measured before and after 0.5, 1,3 and 6 h of the carrageenan injection. Compounds IIIajwere administered at a dose of 10mg/kg body weight, 0.5h before the carrageenan injection. The results showed 36.69, 45.87 and 31.19% inhibition of edematous volume at third hour against carrageenan induced paw edema.The compounds IIIa, IIIbandIIIcwere screened for analgesic activity and measured by noting the writhing response by acetic acid in mice gave 43.01, 34.05 and 26.24% of protection against acetic acid induced writhing, respectively. These results confirm the encouraging anti-inflammatory and analgesic activity of the metal complexes of coumarins Schiff bases.

The study was designed to investigate the hepatoprotective activity of methanol extract of Cissus quadrangularis against rifampicin-induced hepatotoxicity in rats.The coarse powder of the shade dried stem of Cissus quadrangularis was subjected to successive extraction in a Soxhlet apparatus using solvents petroleum ether (60-80°) and methanol. Liver damage was induced in Wistar rats by administering rifampicin (54 mg/kg, p.o.) once daily for 30 days. Methanol extract of Cissus quadrangularis (500 mg/kg, p.o) was administered 1 h prior to the administration of rifampicin (54 mg/kg, p.o.) once daily for 30 days. Silymarin (50 mg/kg p.o) used as reference drug. Elevated levels of aspartate transaminase, alanine transaminase, alkaline posphatase and bilirubin following rifampicin induction were significantly lowered due to pretreatment with methanol extract of Cissus quadrangularis. Rifampicin administration significantly increased lipid peroxidation and decreased antioxidant activities like reduced glutathione, superoxide dismutas and catalase. Pretreatment of rats with methanol extract of Cissus quadrangularis significantly decreased lipid peroxidation and increased the antioxidant activities. Histology of the liver section of the animals treated with the methanol extract of Cissus quadrangularis further confirms the hepatoprotective activity. The results of the present study indicated the hepatoprotective effect of methanol extract of Cissus quadrangularis which might be ascribable to its antioxidant property due to the presence of β-carotene.

Objective: The present investigation was undertaken to explore the possible mechanisms of Plectranthus amboinicus leaf extract in alloxan-induced diabetic rats. Materials and Methods: Control and alloxan-induced diabetic albino rats received different treatments; orally control (vehicle), 200 mg/kg and 400 mg/kg of ethanol extract of Plectranthus amboinicus (PAEE) and 600 μg/kg of glibenclamide (standard) for 15 days. At the end of the experiment, the animals were sacrificed and enzyme activities of carbohydrate metabolism were measured in the liver. Results: Diabetic control rats showed a significant elevation (P < 0.001) in fasting blood glucose on successive days of the experiment as compared with their basal values, which was maintained over a period of 2 weeks. Daily oral treatment with PAEE showed a significant reduction (P < 0.001) in the blood glucose levels on successive days of the experiment as compared with their basal values. The most pronounced antihyperglycemic effect was obtained with the dose of 400 mg/kg. PAEE shows a dose-dependent reduction in gluconeogenic enzymes like glucose-6-phosphatase and fructose-1,6-disphosphatase. After 15 days of treatment with PAEE, glycolytic enzymes like phosphoglucoisomerase resulted in a significant increase with a concomitant significant decrease in the activities of aldolase. On the other hand, glucose-6-phosphate dehydrogenase was significantly improved in diabetic rats on administration of PAEE; the 400 mg/kg dose of PAEE elicited a more potent effect compared with the 200 mg/kg dose. Conclusion: The results obtained in this study provide evidence of the antidiabetic activity of PAEE, mediated through the regulation of carbohydrate metabolic enzyme activities.

Objective: The study was designed to investigate the hepatoprotective activity of methanol extract of Cissus quadrangularis (CQ) against isoniazid-induced hepatotoxicity in rats. Materials and Methods: The successive petroleum ether (60–80°C) and methanol extracts of C. quadrangularis were used. Hepatic damage was induced in Wistar rats by administering isoniazid (54 mg/kg, p.o.) once daily for 30 days. Simultaneously, CQ (500 mg/kg p.o) was administered 1 h prior to the administration of isoniazid (54 mg/kg, p.o.) once daily for 30 days. Silymarin (50 mg/kg p.o) was used as a reference drug. Results: Elevated levels of aspartate transaminase, alanine transaminase, alkaline posphatase, and bilirubin following isoniazid administration were significantly lowered due to pretreatment with CQ. Isoniazid administration significantly increased lipid peroxidation (LPO) and decreased antioxidant activities such as reduced glutathione, superoxide dismutase, and catalase. Pretreatment of rats with CQ significantly decreased LPO and increased the antioxidant activities. Conclusion: The results of this study indicated that the hepatoprotective effect of CQ might be attributed to its antioxidant property.

Objective : To investigate the preventive and curative role of ascorbic acid on doxorubicin (dox)-induced myocardial toxicity in rats. Materials and Methods : Animals were divided into five groups of six animals each. Group I served as normal control and received saline 5 ml/kg/day intraperitoneal (i.p.) for a period of 15 days. Group II animals received ascorbic acid 20 mg/kg per oral (p.o.) for 15 days as a pretreatment control (PR). Group III animals received dox 2.5 mg/kg body weight (b.w.), i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. Group IV animals received ascorbic acid 20 mg/kg p.o. for 15 days as a pretreatment followed by dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg body weight. Group V animals received dox 2.5 mg/kg b.w., i.p., in six equal injections for two weeks for a total cumulative dose of 15 mg/kg b.w. followed by ascorbic acid 20 mg/kg p.o for 15 days as post-treatment control (CR). The biochemical parameters such as tissue glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), and enzyme biomarkers such as creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were monitored. Results : Pretreatment with ascorbic acid (20 mg/kg p.o.) significantly protected the myocardium from the toxic effect of dox (PR), by increasing the levels of antioxidant enzymes such as GSH, SOD, and CAT toward normal and decreased the levels of MDA, CPK, LDH, AST, and ALT as compared with dox-treated rats. Post-treatment with ascorbic acid to dox-treated group (CR) significantly increased the levels of tissue GSH, SOD, CAT and significantly decreased the level of MDA as compared with dox-treated group. It also reduced the severity of cellular damage of the myocardium as confirmed by histopathology. The restoration of the endogenous antioxidant system clearly depicts that ascorbic acid produced its protective effect by scavenging the reactive oxygen species. Conclusion : The results obtained in this study provide evidence for the usefulness of the ascorbic acid as a cardioprotective agent.

Objectives: To investigate the effect of the aqueous extract of Phyllanthus niruri (Aq.E.PN) against doxorubicin (Dox)-induced myocardial toxicity in rats. Materials and Methods: Cardiotoxicity was produced by Dox administration (15 mg/kg for 2 weeks). Aq.E PN (200 mg/kg, orally) was administered as pretreatment for 2 weeks alternated with Dox for the next 2 weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), creatinine phosphokinase (CPK) and alkaline phosphatase, diagnostic enzyme markers like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and antioxidants such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were monitored after 3 weeks of the last dose. Results: Pretreatment with the Aq.E.PN significantly (P < 0.01) protected the myocardium from the toxic effects of Dox by reducing the elevated level of biomarker and diagnostic enzymes like LDH, CPK, AST and ALT to the normal levels. Aq.E PN increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Administration of Dox caused cardiomyopathy associated with an antioxidant deficiency. Conclusion: These results suggest a cardioprotective effect of P. niruri due to its antioxidant properties.

In this study, some neuropharmacological effects of methnolic root extract of Cissus quadrangularis Linn. (CQ) belongs to family Vitaceae were studied in mice using various models. The CQ root extract significantly inhibited acetic acid-induced writhings and increased tail flick withdrawal response in mice. The effects of CQ on CNS were studied by using, spontaneous motor activity, exploratory behaviour, rota-rod performance and potentiation of pentobarbitone sleeping time in mice. Preliminary phytochemical evaluation and acute toxicity values were also carried out and LD50 was found to be 1000 mg/kg by i p route. The extract (50,100 and 200 mg/kg i. p.) produced reduction in spontaneous motor activity, exploratory behaviour and motor coordination and prolonged pentobarbitone sleeping time. Preliminary qualitative chemical studies indicated the presence of triterpenoids, flovonols, sapononis, and alkaloids in the extract. The results suggest that the methanolic root extract of CQ contains some active principles, which may be sedative in nature. (Afr. J. Biomed. Res. 9:69 – 75, May 2006) Keywords: Cissus quadrangularis; Sedation; Spontaneous motor activity, Exploratory Behaviour, Motor coordination, Pentobarbital sleeping time

The present study was designed to compare the curative role of proton pump inhibitors, omeprazole, rabeprazole and lansoprazole against dexamethasone-induced ulcer model. Dexamethasone (5 mg/kg/day) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all rats. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 minutes prior to dexamethasone for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as estimation of myeloperoxidase, cortisol, alkaline phosphatase, malondialdehyde, endogenous anti-oxidants like superoxide dismutase, catalase and reduced glutathione. In dexamethasone induced ulcer model, omeprazole showed significant decrease in malondialdehyde, myeloperoxidase, alkaline phosphatase level and increase in superoxide dismutase, catalase and reduced glutathione level as compared to rabeprazole and lansoprazole. Omeprazole showed significant reduction in cortisol content where as rabeprazole and lansoprazole did not show significant changes as compared to control. The result indicates that omeprazole is the most effective and selective proton pump inhibitor in dexamethasone induced ulcer model as compared to rabeprazole and lansoprazole.

Objective: The present study was designed to investigate the protective and potential effect of gallic acid against doxorubicin (DOX) induced cardiotoxicity. Materials and Methods: Adult Wistar albino rats of either sex weighing 150-200 g were used in this study. DOX administered intraperitoneally in six equal injections (each containing 2.5 mg/kg at 48 h intervals) to total cumulative doses of 15 mg/kg over a period of 2 weeks to induce cardiotoxicity. The estimation of cardiac and lipid biomarkers of both control and treated animals were observed. In vivo antioxidant parameters such as glutathione, superoxide dismutase, catalase, and malondialdehyde were also monitored. The remaining portion of the heart tissue used for histopathological studies. Results: The treatment with doxorubicin increased the levels (P > 0.01) of serum cardiac and lipid biomarker which were brought down by gallic acid treatment. It also exhibited electrocardiographic changes such as reduced R wave and ST segment elevation. Histopathological study revealed that gallic acid restored the myocardial cells towards normal. The restoration of the endogenous antioxidant system clearly depicts that gallic acid have produced its protective effect by scavenging the reactive oxygen species. Conclusion: The results of this study indicated that the cardioprotective effect of gallic acid might be attributed to its antioxidant property.

Objectives: Cardioprotective activity of alcoholic extract of Saraca indica (SI) bark was investigated against cyclophosphamide induced cardiotoxicity. Materials and Methods: Cardiotoxicity was induced in Wistar rats by administering cyclophosphamide (200 mg/kg, i.p.) single injection on first day of experimental period. Saraca indica (200 and 400 mg/kg, p.o.) was administered immediately after administration of cyclophosphamide on first day and daily for 10 days. The general observations and mortality were measured. Results: Cyclophosphamide administration significantly (p < 0.05) increased lipid peroxidation (LPO) and decreased the levels of antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Cyclophosphamide elevated the levels of biomarker enzymes like creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Further, the cyclophosphamide treated rats showed changes in electrocardiogram (ECG) along with increased levels of cholesterol and triglycerides. Treatment with Saraca indica significantly (p < 0.05) reversed the status of cardiac biomarkers, ECG, oxidative enzymes and lipid profile in cyclophosphamide induced cardiotoxicity. Potential cardioprotective effect of Saraca indica was supported by histopathological examination that reduced severity of cellular damage of the myocardium. Conclusion: The biochemical, ECG and histopathology reports support the cardioprotective effect of Saraca indica which could be attributed to antioxidant activity.