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  • Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity.

Hypericin maintians PDX1 expression via the Erk pathway and protects islet β-cells against glucotoxicity and lipotoxicity.

International journal of biological sciences (2019-07-25)
Chen Liang, Fang Hao, Xinlei Yao, Ye Qiu, Lei Liu, Shuyue Wang, Chunlei Yu, Zhenbo Song, Yongli Bao, Jingwen Yi, Yanxin Huang, Yin Wu, Lihua Zheng, Ying Sun, Guannan Wang, Xiaoguang Yang, Shaonian Yang, Luguo Sun, Yuxin Li
ABSTRACT

A decrease in islet β-cell mass is closely associated with the development and progression of diabetes. Therefore, protection against β-cell loss is an essential measure to prevent and treat diabetes. In this study, we investigated the protective effects of non-photoactivated hypericin, a natural compound, on β-cells both in vitro and in vivo. In vitro, hypericin greatly improved INS-1 cell viability under high-glucose and high-fatty-acid conditions by inhibiting glucotoxicity- and lipotoxicity-induced apoptosis and nitric oxide (NO) production. Then, we further demonstrated that hypericin elicited its protective effects against glucotoxicity and lipotoxicity in INS-1 cells by attenuating the reduction in pancreatic duodenal homeobox-1 (PDX1) expression and Erk activity. In vivo, prophylactic or therapeutic use of hypericin inhibited islet β-cell apoptosis and enhanced the anti-oxidative ability of pancreatic tissue in high-fat/high-sucrose (HFHS)-fed mice, thus alleviating β-cell loss and maintaining or improving β-cell mass and islet size. More importantly, hypericin treatment decreased fasting blood glucose, improved glucose intolerance and insulin intolerance, and alleviated hyperinsulinaemia in HFHS-fed mice. Therefore, hypericin showed preventive and therapeutic effects against HFHS-induced onset of type II diabetes in mice. Hypericin possesses great potential for development as an anti-diabetes drug in the future.