Antidiabetic, Antihyperlipidemic and Antioxidant Activities of Buchanania lanzan Spreng Methanol Leaf Extract in Streptozotocin-Induced Types I and II Diabetic Rats

Purpose: To evaluate the antidiabetic, antihyperlipidemic and antioxidant activities of Buchanania lanzan.Methods: Wistar rats were divided into nine groups of six animals each, and 40 mg/kg of streptozotocin or streptozotocin + nicotinamide was administered intraperitonially to induce types I and II diabetes. Those with blood glucose levels > 190 ± 8 mg/dl were administered the methanol leaf extract of Buchanania lanzan (MEBL, 100 or 200 mg/kg, p.o.) or positive control for 21 days. Blood glucose, lipid profile, antioxidant enzymes and oxidative stress markers were evaluated.Results: Following induction, blood glucose level rose to 327.7 ± 47.4 mg/dl, compared to the normal value of 910 ± 3.2 mg/dl. Administration of MEBL (100 or 200 mg/kg) significantly (p < 0.05) decreased blood glucose level, serum lipid profile, and significantly (p < 0.05) increased antioxidant activity as evidenced by increase in super oxide dismutase (SOD), catalas, glutathione (GSH), and decrease in the activity of lipid peroxidation (LPO).Conclusion: MEBL exhibits antidiabetic, antihyperlipidemic and antioxidant activities in diabetic rat and needs to be further investigated for the treatment of both types I and II diabetes mellitus.Keywords: Antidiabetic, Antihyperlipidemic, Antioxidant, Buchanania lanzan

Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation

<p>Abstract</p> <p>Background</p> <p>Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC.</p> <p>Methods</p> <p>Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589.</p> <p>Results</p> <p>The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays.</p> <p>Conclusions</p> <p>We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.</p

Antidiabetic, Antihyperlipidemic and Antioxidant Activities of Buchanania lanzan Spreng Methanol Leaf Extract in Streptozotocin-Induced Types I and II Diabetic Rats

Purpose: To evaluate the antidiabetic, antihyperlipidemic and antioxidant activities of Buchanania lanzan.Methods: Wistar rats were divided into nine groups of six animals each, and 40 mg/kg of streptozotocin or streptozotocin + nicotinamide was administered intraperitonially to induce types I and II diabetes. Those with blood glucose levels &gt; 190 ± 8 mg/dl were administered the methanol leaf extract of Buchanania lanzan (MEBL, 100 or 200 mg/kg, p.o.) or positive control for 21 days. Blood glucose, lipid profile, antioxidant enzymes and oxidative stress markers were evaluated.Results: Following induction, blood glucose level rose to 327.7 ± 47.4 mg/dl, compared to the normal value of 910 ± 3.2 mg/dl. Administration of MEBL (100 or 200 mg/kg) significantly (p &lt; 0.05) decreased blood glucose level, serum lipid profile, and significantly (p &lt; 0.05) increased antioxidant activity as evidenced by increase in super oxide dismutase (SOD), catalas, glutathione (GSH), and decrease in the activity of lipid peroxidation (LPO).Conclusion: MEBL exhibits antidiabetic, antihyperlipidemic and antioxidant activities in diabetic rat and needs to be further investigated for the treatment of both types I and II diabetes mellitus.Keywords: Antidiabetic, Antihyperlipidemic, Antioxidant, Buchanania lanzan