R. Balaraman

Time-dependent changes in antioxidant enzymes and vascular reactivity of aorta in streptozotocin-induced diabetic rats treated with curcumin.

In the present study changes in oxidative stress and vascular reactivity in aortic rings of chronic streptozotocin-diabetic (STZ-CON) and nondiabetic (ND-CON) rats is studied at 4 weekly intervals up to 24 weeks. The effect of chronic curcumin (200 mg/kg) treatment was also studied. Blood glucose and blood pressure levels were significantly higher in the STZ-CON group and curcumin administration had no significant effect on it. Superoxide dismutase and catalase activity were either unchanged or significantly increased during the early stage of diabetes whereas during the medium and late stage were significantly reduced. Reduced glutathione and lipid peroxidation levels significantly decreased as time after STZ administration increased. Phenylephrine (PE)-induced contraction was significantly (P < 0.05) increased during the early stage of diabetes, whereas it was significantly (P < 0.05) reduced at the medium and late stage of diabetes. Acetylcholine (Ach)-induced relaxation significantly decreased with respect to time after STZ administration. Sodium nitroprusside (SNP)-induced relaxation was unaltered up to initial stage but after medium stage there was a rightward shift and the pD2 value significantly decreased. Though curcumin treatment had no significant effect on superoxide dismutase, catalase, and reduced glutathione levels, it significantly reduced lipid peroxidation compared with diabetic control. Curcumin treatment attenuated the phenylephrine-induced increase in contraction during the early stage. However, curcumin treatment had no significant effect at the medium and late stage. Though curcumin administration improved Ach-induced relaxation it did not restore it to normal. Inability of curcumin to prevent oxidative stress during the late stage may be due to the fact that chronic diabetes (hyperglycemia) leads to excessive production of free radicals. Hence the present study shows that variations reported in antioxidant enzymes and vascular reactivity are due to the duration of diabetes or time after diabetes induction in STZ model and this can not be completely reversed by chronic treatment with curcumin.

Antiovulatory and abortifacient potential of the ethanolic extract of roots of Momordica cymbalaria Fenzl in rats

Objective: To study the antiovulatory and abortifacient activity of the ethanolic extract of roots of Momordica cymbalaria Fenzl. n Materials and Methods: Female Wistar albino rats (150 to 200 g) with at least three regular estrous cycles were administered ethanolic extracts of roots of Momordica cymbalaria Fenzl. at two doses 250 and 500 mg/kg orally for 15 days. Control group received vehicle (tween 80 1%, p.o. daily). Animals were sacrificed on 16th day. One ovary was subjected to histopathological studies and the other for biochemical studies. Abortifacient study was done in another set of three groups of animals. The extracts at doses of 250 and 500 mg/kg were administered orally through gastric gavage from the day 6 to day15 of pregnancy (the period of organogenesis). The animals were laparotomised under light ether anesthesia and semi- sterile conditions on day 19th of pregnancy. Both horns of the uterus were observed for the number of implantation sites, resorptions, dead and alive foetus. n Results: Highly significant (P<.001) decrease in the duration of estrous cycle and metaestrous phase and increase in proestrous phase was seen, but diestrous phase was unchanged in both 250 and 500 mg treated group when compared to untreated group. Significant decrease in the ovarian weight and a highly significant increase in serum cholesterol with 250 mg/kg dose were seen. Histology of ovary showed an increase in preovulatory and atretic follicles. Ethanolic extract showed a dose dependent abortifacient effect in pregnant rats during organogenesis period. At 250 mg/kg ethanolic extract did not show any abortifacient activity but reduced the number of viable foetus and resorptions with no change in the foetal weight when compared with control group. At 500 mg/kg ethanolic extract showed highly significant (P< 0.001) abortifacient activity. n Conclusion: The ethanolic extract at both doses (250 and 500 mg/kg) showed antiovulatory activity. It is abortifacient at 500 mg/kg but not at 250 mg/kg.

Antiimplantation activity of the ethanolic root extract of Momordica cymbalaria Fenzl in rats

Objective : To evaluate the antiimplantation activity of the ethanolic root extract of Momordica cymbalaria Fenzl. Materials and Methods : The acute oral toxicity study was performed according to the OPPTS guidelines. The ethanolic root extract was investigated for antiimplantation, estrogenic and progestrogenic activities at doses of 250 and 500 mg/kg body weight. Antiimplantation activity was studied on successive stages of embryogenesis. Estrogenic studies were carried out by examining uterine weight, histoarchitecture of uterus, vaginal cornification, uterine content of glucose, cholesterol and alkaline phosphatase levels in immature rats. Progestrogenic activity assay was performed by pregnancy maintenance in rats and Claubergs test (endometrial proliferation assay) in immature rabbits. Results : Both doses of the ethanolic root extract exhibited highly significant (P Conclusion : The ethanolic root extract of Momordica cymbalaria Fenzl exhibited antiimplantation activity but this is not due to estrogenic or progestrogenic activities.

Synthesis and anti-inflammatory activity of 2,3-diaryl-4(3H)-quinazolinones

Abstract2,3-Diaryl-4(3H)-quinazolinones containing various substituents on diaryl rings have been synthesized and evaluated for their cyclooxygenase-2 inhibitory activity by the colorimetric COX (ovine) inhibitor screening assay and anti-inflammatory activity by the carrageenan-induced rat paw edema assay. 2-(4-Nitrophenyl)-3-(4-tolyl)-4(3H)-quinazolinone showed a maximum COX-2 inhibition of 27.72% at 22 µM concentration in the present series and exhibited a mild anti-inflammatory activity at a dose of 50 mg/kg in carrageenan-induced rat paw edema assay.

Synthesis, antileukemic and antiplatelet activities of 2,3-diaryl-6,7-dihydro-5H-1,4-diazepines

The synthesis, antileukemic and antiplatelet activity evaluation of 2,3-diaryl-6,7-dihydro-5H-1,4-diazepines are described. In general, it was found that compound 17o showed moderate antileukemic activity against MOLT3 human leukemic cancer cell lines. An arachidonic acid induced platelet aggregation effect on washed rat platelets was studied. Compound 17i was found to be the most potent. The antiplatelet properties may be mediated by interference with the arachidonic acid pathway.

Retinol-binding protein 4: a possible role in cardiovascular complications

BACKGROUND AND PURPOSE Retinol‐binding protein 4 (RBP4) is an adipocyte‐secreted hormone proposed to link obesity with insulin resistance. However, the role of RBP4 in cardiovascular complications is yet to be fully understood. The present study is aimed to decipher the association between RBP4 with pro‐inflammatory cytokines and low‐density lipoprotein (LDL) cholesterol in diet‐induced obese and hyperlipidaemic mice. To understand the correlation, rimonabant, an anti‐obesity drug, has been used to relieve the atherosclerotic predisposition.

Subtherapeutic Dose of Pioglitazone Reduces Expression of Inflammatory Adipokines in db/db Mice

Agonists of the thiazolidinedione class of peroxisome proliferator-activated receptor-γ exhibit both insulin-sensitizing and anti-inflammatory effects. We hypothesized that pioglitazone might be able to exert its anti-inflammatory properties at a lower dose than that required for its insulin-sensitizing effect. In order to investigate this hypothesis, we evaluated the effects of pioglitazone on inflammatory as well as metabolic biomarkers in serum and white adipose tissue (WAT) at 2 different doses. Female db/db mice were treated orally with therapeutic (30 mg/kg) and subtherapeutic (3 mg/kg) doses of pioglitazone for 14 days followed by an oral glucose tolerance test. Other parameters measured were inflammatory markers such as tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and metabolic biomarkers in serum (insulin, glucose and adiponectin). Moreover, adiponectin, fatty acid-binding protein (aP2) and lipoprotein lipase (LPL) mRNA expression in WAT were determined by real-time PCR. A subtherapeutic dose of pioglitazone significantly suppresses the expression of TNF-α and IL-6 mRNA in WAT, but does not alter the serum glucose, insulin and WAT expression of adiponectin, adipocyte aP2 and LPL. A therapeutic dose of pioglitazone improves insulin sensitivity, enhances LPL, aP2 and adiponectin expression, and also suppresses TNF-α and IL-6 expression. In conclusion, the current study indicates that the anti-inflammatory effect of pioglitazone is produced at a subtherapeutic dose, which is considerably lower than the dose needed to produce any desired metabolic effects. Anti-inflammatory effects of pioglitazone may precede its insulin-sensitizing effects in db/db mice.

Effect of Atorvastatin Treatment on Isoproterenol-Induced Myocardial Infarction in Rats

In the present study, chronic treatment of atorvastatin was evaluated on isoproterenol-induced myocardial infarction. Male Sprague-Dawley rats (200 ± 25 g) were randomized into the following four groups: (1) control group, (2) isoproterenol-treated group, (3) atorvastatin-treated group, and (4) isoproterenol- and atorvastatin-treated group. Various serum and tissue parameters as well as histopathological studies were carried out in all groups. Isoproterenol administration produced severe myocardial damage and oxidative stress in rats. Atorvastatin treatment reduced myocardial infarction which has been reflected by improvement in serum parameters, ATPase activities and histopathological lesions. However, it could not reduce oxidative stress and hypertrophy induced by isoproterenol. Hence, it can be concluded that atorvastatin may protect myocardial infarction induced by isoproterenol independent of its antioxidant properties.