Effect of combination treatment of S–amlodipine with peroxisome proliferator-activated receptor agonists on metabolic and cardiovascular parameters in Zucker fa/fa rats

BACKGROUND: Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. The available drugs are not sufficiently efficacious in reducing cardiovascular risk and restoring normal glucose metabolism associated with type 2 diabetes as a mono- or a combination therapy. The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats. METHODS: Following combination treatment for 14 days, blood pressure (BP), serum glucose, total cholesterol and triglycerides were measured. Aortic ring study was conducted to determine the effect of combination treatments on phenylephrine-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation. RESULTS: In combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose (115.1 ± 6.6 vs. 81.7 ± 4.2), BP (184.4 ± 5.0 vs. 155.1 ± 5.0), serum triglycerides (362.5 ± 47.5 vs. 211.1 ± 23.7) and glucose intolerance when compared with vehicle treated Zucker fa/fa rats. Similar results were observed with the combination of S-Amlodipine and Ragaglitazar (Triglycerides, 362.5 ± 47.5 vs. 252.34 ± 27.86; BP, 184.4 ± 5.0 vs. 159.0 ± 8.0) except for serum glucose. ACh-induced vasorelaxation in aortic rings was also superior with both of the combinations compared to individual treatment. Furthermore, there was less body weight gain and food intake with S-Amlodipine and Pioglitazone combination in Zucker fa/fa rats. S-Amlodipine itself caused significant reduction in glucose (115.1 ± 6.6 vs. 89.7 ± 2.7) and BP (184.4 ± 5.0 vs. 156.1 ± 4.0) with improvement in insulin sensitivity observed through oral glucose tolerance test. CONCLUSIONS: The results suggest that a combination of PPAR agonists and S-Amlodipine has partial benefits in improving the cardiovascular risk factors such as reduction in triglyceride levels, associated with chronic type 2 diabetes, and therefore may be utilized as an approach for addressing some of these devastating metabolic syndrome complications

Anti-diabetic activity and safety assessment of Ayurvedic medicine, <i style="mso-bidi-font-style:normal">Jasada bhasma</i> (zinc ash) in rats<span style="mso-bidi-font-weight:bold"> </span>

811-822Jasada bhasma (zinc ash) is an extensively used Ayurvedic medicine for treating diabetes mellitus. The present communication presents yet unavailable comprehensive scientific data on its physico-chemical nature vis-à-vis anti-diabetic activity and toxicity profile.Zinc ash prepared by traditional method was found to consist of 200-500 nm sized particles, predominantly zinc oxide with hexagonal wurtzite crystal structure.The effective dose range of zinc ash in oral glucose tolerance tests performed using normoglycemic Wistar rats was found to be 3-30 mg/kg. Subsequently anti-diabetic activity was assessed in streptozotocin induced type 1 and type 2 diabetic rats. Four weeks treatment with zinc ash (1, 3, 10 mg/kg) resulted in improved glucose tolerance (16-19%), lowered blood glucose levels (20-33%) and reduced serum insulin levels (27-32%). Systemic absorption was assessed by single dose pharmacokinetic study where serum zinc levels were found to be elevated (3.5 folds) after oral administration of zinc ash. Acute and sub-acute toxicity tests demonstrated safety of zinc ash up to 300 mg/kg doseie. 100 times the efficacy dose in rats.These findings, the first of their kind, provide concrete scientific evidence that justifies usage of zinc ash in diabetes treatment