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Article Publish Status: FREE
Abstract Title:

Involvement of Estrogen Receptor-α in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic β-Cells.

Abstract Source:

Biomol Ther (Seoul). 2019 Oct 25. Epub 2019 Oct 25. PMID: 31649209

Abstract Author(s):

Chun Chu, Xiang Gao, Xiang Li, Xiaoying Zhang, Ruixin Ma, Ying Jia, Dahong Li, Dongkai Wang, Fanxing Xu

Article Affiliation:

Chun Chu

Abstract:

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreaticβ-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Ourstudy revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin- induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggeststhat silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

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