A cross talk study on sitagliptin mediated reclamation on TGF ß signalling, DPP 4, miR-29a and miR-24 expression in PCOS rats fed with high fat-high fructose diet.

Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive, endocrine and metabolic disturbance which is very commonly observed in females of reproductive age group. The disease is still incurable however the use of synthetic drugs in combination with lifestyle is recommended. Accordingly, the present study was conducted to investigate the possible beneficial effects of sitagliptin on PCOS induced rats on control diet (CD)/high fat- high fructose diet (HFFD). PCOS was induced by giving testosterone propionate (TP) for 28 days to both the CD/HFFD rats and treated with STG i.p. for last 15 days. At the end of the experiment lipid profile, inflammatory markers, expression of NF-κB-p65, miR-24 and miR-29a, fibrotic and apoptotic proteins from ovary tissue were examined. Moreover, lipid accumulation and fibrosis of ovary tissue was further confirmed using Sudan III and Masson's trichrome stain. STG treated rats exerted a significant decrease in levels of cholesterol, TG, LDL-C, VLDL-C, IL-6 and TNF-α and increased HDL-C level, miR-24 and miR-29a expression. STG treated groups expressed significantly decreased expression of NF-κB-p65, TGF-ß1, p-Smad 2 and p-Smad 3 followed by no significant changes in the expression of BAX, caspase-9, caspase-3 and Bcl-2 in all the PCOS induced groups. Among all the CD/ HFFD fed groups, rats on HFFD showed more devastating effect which suggests that diet plays a major role in genesis of PCOS. In conclusion, current results reflect the potential impact of STG against dyslipidaemia, inflammation and fibrosis in PCOS rats via regulating dyslipidaemia and fibrosis via DPP 4 mediated miR-29a expression.

Evaluation of Serum miRNA-24, miRNA-29a and miRNA-502-3p Expression in PCOS Subjects: Correlation with Biochemical Parameters Related to PCOS and Insulin Resistance.

MicroRNAs (miRNAs) are small, endogenous, non-coding, single stranded RNAs which play a role in the regulation of gene expression and function. Therefore, the analysis of differentially expressed miRNAs are of great importance in disease diagnosis. This study is focussed on the differential expression of miRNAs in serum of PCOS subjects compared to control and their correlation with metabolic and endocrine parameters. Anthropometry, hormone concentrations and biochemical characteristics were measured in healthy (n = 20) and PCOS (n = 20) subjects. MiR-24, miR-29a and miR-502-3p were determined in serum by quantitative RT-PCR. The levels of miR-24 was significantly decreased in PCOS subjects (P = 0.00) compared to control. No significant difference was observed in the levels of miR-29a and miR-502-3p in PCOS and control subjects. MiR-24 showed significant inverse correlation with BMI, glucose, insulin, FIRI, HOMA, LH, testosterone, TG, and LH:FSH ratio whereas HDL levels showed significant positive association with miR-24 and miR-29a. LH showed significant negative association with miR-29a. No correlation was observed between the expression of miR-502-3p with any of the studied parameters. The receiver operating characteristic curve for miR-24 alone showed a significant discriminative capacity. The study suggests that serum miR-24 analysis in PCOS patients could be of diagnostic value that can be used as a biomarker for PCOS.

Apigenin attenuates hippocampal oxidative events, inflammation and pathological alterations in rats fed high fat, fructose diet.

High calorie diet promotes oxidative stress and chronic low grade inflammation that predispose to brain dysfunction and neurodegeneration. Hippocampus region of the brain has been shown to be particularly sensitive to high calorie diet. We hypothesize that apigenin (API), a flavonoid could attenuate hippocampal derangements induced by high fat-high fructose diet (HFFD). In this study, we investigated the effects of API on oxidative stress and inflammation in the hippocampus, and compared with those of sitagliptin (STG), a standard drug with neuroprotective properties. The markers of oxidative stress and inflammation were examined using biochemical assays, western blotting and immunohistochemistry techniques. HFFD-fed rats showed severe pathological alterations and API treatment rescued the hippocampus from the derangements. API significantly improved the antioxidant machinery, reduced ROS levels and prevented the activation of the stress kinases, inhibitor of kappa B kinase beta (IKKß) and c-Jun NH2 terminal kinase (JNK), and the nuclear translocation and activation of nuclear factor kappa B (NF-κB). The plasma levels of inflammatory cytokines were also reduced. Our findings suggest that hippocampal derangements triggered by HFFD feeding were effectively curtailed by API. Suppression of oxidative stress, NF-κB activation and JNK phosphorylation in the hippocampus are the mechanisms by which API offers neuroprotection in this model.

Antihyperglycemic effect of the alcoholic seed extract of Swietenia macrophylla on streptozotocin-diabetic rats.

BACKGROUND: Streptozotocin (STZ) selectively destroys the pancreatic insulin secreting cells, leaving less active cells and resulting in a diabetic state. The present study was designed to investigate the antihyperglycemic effect of the ethanolic seed extract of Swietenia macrophylla (SME) in normal and STZ-diabetic rats. MATERIALS AND METHODS: The experimental groups were rendered diabetic by intraperitoneal injection of a single dose of STZ (40 mg/kg body weight [BW]). Rats with glucose levels > 200 mg/dL were considered diabetic and were divided into 5 groups. Three groups of diabetic animals were orally administered, daily with seed extract at a dosage of 50, 100, and 200 mg/kg BW. One group of STZ rats was treated as diabetic control and the other group was orally administered 600 µg/kg BW glibenclamide daily. RESULTS: Graded doses of seed extract and glibenclamide showed a significant reduction in blood glucose levels and improvement in serum insulin levels. The extract also improved body weight and promoted liver glycogen content. After treatment, hemoglobin (Hb) level increased and glycosylated Hb level significantly decreased in diabetic rats. The activities of the carbohydrate metabolic enzymes showed significant changes in the rats. Of the 3 doses, 100 mg dose showed maximum activity. Histological investigations of pancreas also supported the biochemical findings. CONCLUSIONS: Thus, our findings indicate the folklore use of the seed for diabetes and the mechanism seems to be insulin secretion.