Deoxyactein protects pancreatic β-cells against methylglyoxal-induced oxidative cell damage by the upregulation of mitochondrial biogenesis

Suh,Kwang  Sik; Choi,Eun  Mi; Jung,Woon-Won; Kim,Yu  Jin; Hong,Soo  Min; Park,So  Yong; Rhee,Sang  Youl; Chon,Suk

doi:10.3892/ijmm.2017.3018

Deoxyactein protects pancreatic β-cells against methylglyoxal-induced oxidative cell damage by the upregulation of mitochondrial biogenesis

Authors:
- Kwang Sik Suh
- Eun Mi Choi
- Woon-Won Jung
- Yu Jin Kim
- Soo Min Hong
- So Yong Park
- Sang Youl Rhee
- Suk Chon
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Affiliations: Research Institute of Endocrinology, Kyung Hee University Hospital, Seoul 130-702, Republic of Korea, Department of Endocrinology and Metabolism, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea, Department of Biomedical Laboratory Science, College of Health Sciences, Cheongju University, Cheongju, Chungbuk 360-764, Republic of Korea, Department of Medicine, Graduate School, Kyung Hee University, Seoul 130-702, Republic of Korea
Published online on: June 12, 2017 https://doi.org/10.3892/ijmm.2017.3018
Pages: 539-548

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Abstract

Methylglyoxal (MG) is one of the major precursors of advanced glycation end products (AGEs), which are considered to be one of the causes of diabetes and its complications. The root and rhizomes of black cohosh (Cimicifuga racemosa) have long been used medicinally, and deoxyactein is one of its major constituents. In the present study, the protective effects of deoxyactein against MG-induced oxidative cell damage were investigated in insulin-producing pancreatic β-cells. We found that deoxyactein protected the pancreatic β-cells against MG-induced cell death. Pre-treatment with deoxyactein significantly reduced the levels of intracellular reactive oxygen species (ROS), interleukin-1β (IL-1β), cardiolipin peroxidation, and protein adduct accumulation induced by MG. Pre-treatment of the cells with deoxyactein restored glyoxalase I activity and insulin secretion which were reduced by MG, and increased the mRNA expression of insulin 2 (INS2) and pancreatic and duodenal homeobox protein-1 (PDX-1). It also increased the levels of endogenous antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, treatment with deoxyactein increased the levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). These findings indicate that deoxyactein may exert beneficial effects on pancreatic β-cells via the upregulation of mitochondrial biogenesis. Taken together, these results suggest that deoxyactein may be used for the prevention of pancreatic β-cell damage.

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