Studies on the Effect of Piperine on Hepatocyte Nuclear Factor 1 Alpha (HNF-1α) and Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) Levels in High-Fat-Diet and Sucrose-Induced Type 2 Diabetes Mellitus Rats.

Background: Piperine, a naturally occurring compound in black pepper ( Piper nigrum ), is known for its potential health benefits, including its reported enhancement of insulin sensitivity. However, the precise impact of piperine on hepatocyte nuclear factor 1 alpha (HNF-1α) and sterol regulatory element-binding protein 1c (SREBP-1c), transcription factors for insulin signaling and glucose metabolism in hepatocytes, remains unclear.
Objective: This study aims to investigate the effect of piperine, compared to metformin, on blood glucose and insulin levels by modifying the expression of hepatic HNF-1α and SREBP-1c in high-fat-diet (HFD) and sucrose-induced type 2 diabetes mellitus (T2DM) rats and in human Chang liver cells.
Methods: Adult male albino rats were categorized into four groups: group 1 as the control, group 2 as T2DM, group 3 as T2DM rats treated with piperine (40 mg), and group 4 as T2DM rats treated with metformin (50 mg). Fasting blood glucose (FBG) and serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), while real-time polymerase chain reaction (RT-PCR) analysis was conducted to assess the mRNA expression of HNF-1α and SREBP-1c. Further, piperine was treated with normal and high glucose-induced Chang liver cells, and gene expression was analysed. Data analysis was performed using one-way analysis of variance (ANOVA), with a significance set at p<0.05.
Results: Treatment with piperine led to a notable decrease in blood glucose levels and circulating insulin when compared with T2DM rats (group 2). Additionally, piperine administration resulted in the upregulation of HNF-1α mRNA expression and downregulation of SREBP-1c mRNA levels whose effects were found to be near that of the control and standard drug metformin's effects. In vitro study also confirmed that piperine improved the HNF-1α expression and reduced the expression of SREBP-1c in Chang liver cells.
Conclusion: Our findings suggest that piperine treatment effectively regulates hyperglycemic and hyperinsulinemic insulin resistance in the liver by modulating the expression of HNF-1α and SREBP-1c. Consequently, piperine emerges as a promising candidate for therapeutic intervention in managing T2DM.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright © 2024, Zuvairiya et al.)