Quercetin mitigates hepatic injury by inhibiting TGF-β/p-Smad3 signaling pathway activation and enhancing AMPK activity in type 2 diabetic rats

Abstract

Objective: To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.

Methods: Four groups of 32 rats were used in this study: three groups were given streptozotocin to induce diabetes, and one group was given a normal control. For treatment groups, each group received either metformin (200 mg/kg body weight) or quercetin (50 mg/kg body weight) for a month. The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins (TGF-β and p-Smad3) was evaluated by Western blot. Furthermore, MCP and IL-1β were determined by ELISA.

Results: Quercetin significantly reduced insulin and glucose levels. Besides, it reduced the serum levels of ALT, AST, and ALP, improved lipid profile, lowered the MDA level, increased SOD activity, decreased the rise in MCP-1 and IL-1β, inhibited the TGF-β/Smad3 signaling pathway, decreased α-SMA and SREBP1c expression, and increased AMPK (P<0.05).

Conclusions: Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.

Keywords

Quercetin / Metformin / Streptozotocin / Liver injury / TGF-β/Smad signaling / AMPK / SREBPlc