Effect of Piperine on an Nrf2/Keap 1 Signalling Mechanism in Adipose Tissue of High Fat Diet and Sucrose-Induced Experimental Diabetic Rats

Abstract

Piperine, an alkaloid compound found in black pepper has been shown to have various health benefits such as anti-oxidants, anti-inflammatory, and anticancer activities. But mechanisms underlying the anti-diabetic activity are unclear. Keap1-Nrf2 is an anti-oxidant stress signal pathway and it is considered to be an intracellular defence mechanism to countered oxidative stress. The study was aimed at assessing antidiabetic activity of piperine against high fat diet and sucrose-induced (HFD) type-2 diabetic rats by regulating the expression of Nrf2/Keap 1 signalling. Healthy adult male albino rats of wistar strain were grouped in to 5. Considering healthy control (group-1), HFD-induced type-2 diabetes (group2), Diabetic rats treated with piperine (group 3), diabetic rats metformin (group 4) and control +Piperine treated rats ( group 5) respectively. After 30 days of treatment, fasting blood glucose (FBG) checked and adipose tissue from control and treated groups was used to determine the role of piperine on the expression of NrF2/Keap 1 mNRA in adipose by Real Time-PCR analysis. Data were analysed by one-way ANOVA and p<0.01 was considered to be statistical significance among the groups. HFD-induced T2DM showed a significant increase in the levels of FBG and altered levels of Nrf-2 and Keap-1 gene expression (2 fold) compared to normal control animals. Piperine at a dose of 40mg, fascinatingly improved the glycemic control and normalised the mRNA expression of both Nrf-2 and Keap-1 whose effects were near to that of standard drug metformin level (p<0.05) proving its potential mechanism of action. Conclusion: Our current study clearly indicates that piperine controls hyperglycemia in type-2 diabetic rats by facilitating the expression of antioxidant signalling (Nrf-2/Keap-1) in the adipose. In addition, this is the first of its kind to show the role of piperine in reducing hyperglycemia against high fat diet and sucrose –induced type-2 diabetic rats as an invivo experimental model. Hence, piperine could be considered as an important health supplement and potential drug candidate for the treatment of diabetes.