biostudies-literatureUnknown28(2)Chu CSilibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic ?-cells through up-regulation of estrogen receptor-? (ER?) expression. However, the underlying protective mechanism of silibinin in pancreatic ?-cells is still unclear. In the current study, we sought to determine whether ER? acts as the target of silibinin for the modulation of antioxidative response in pancreatic ?-cells under high glucose and high fat conditions. Our in vivo study 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 ER?, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic ?-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 ER?, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ER? antagonist (MPP) in INS-1 cells or silencing ER? expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic ?-cells through regulation of ER? expression.Biomolecules & therapeutics163-171https://www.ebi.ac.uk/biostudies/studies/S-EPMC7059807biostudies-literatureInvolvement of Estrogen Receptor-? in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic ?-Cells.PMC7059807Li XChu CMa RLi DZhang XWang DJia YXu FGao XfalseInvolvement of Estrogen Receptor-? in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic ?-Cells.Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic ?-cells through up-regulation of estrogen receptor-? (ER?) expression. However, the underlying protective mechanism of silibinin in pancreatic ?-cells is still unclear. In the current study, we sought to determine whether ER? acts as the target of silibinin for the modulation of antioxidative response in pancreatic ?-cells under high glucose and high fat conditions. Our in vivo study 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 ER?, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic ?-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 ER?, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ER? antagonist (MPP) in INS-1 cells or silencing ER? expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic ?-cells through regulation of ER? expression.2020-01-01T00:00:00Z2020 Mar2020-05-22T14:51:56Z2020-05-22T14:51:56ZS-EPMC70598073164920910.4062/biomolther.2019.071