Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Involvement of Estrogen Receptor-α in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic β-Cells

  • Chu, Chun (Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University) ;
  • Gao, Xiang (Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University) ;
  • Li, Xiang (Qiqihaer Middle School) ;
  • Zhang, Xiaoying (Department of Food Quality and Safety, Faculty of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Ma, Ruixin (Department of Food Quality and Safety, Faculty of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Jia, Ying (Department of Food Quality and Safety, Faculty of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Li, Dahong (Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University) ;
  • Wang, Dongkai (Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University) ;
  • Xu, Fanxing (Wuya College of Innovation, Shenyang Pharmaceutical University)
  • Received : 2019.04.28
  • Accepted : 2019.09.04
  • Published : 2020.03.01
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Abstract

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-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. 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 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 suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

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References

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