Emodin Alleviates High-Glucose-Induced Pancreatic β-Cell Pyroptosis by Inhibiting NLRP3/GSDMD Signaling

Yiqian Xing; Yuchi He; Yuan Zhang; Heting Wang; Sihan Peng; Chunguang Xie; Jian Kang; Ya Liu; Xiyu Zhang

doi:10.1155/2022/5276832

Emodin Alleviates High-Glucose-Induced Pancreatic β-Cell Pyroptosis by Inhibiting NLRP3/GSDMD Signaling

Evid Based Complement Alternat Med. 2022 Feb 27:2022:5276832. doi: 10.1155/2022/5276832. eCollection 2022.

Authors

Yiqian Xing¹, Yuchi He¹, Yuan Zhang², Heting Wang³, Sihan Peng¹, Chunguang Xie⁴, Jian Kang⁵, Ya Liu⁶, Xiyu Zhang⁴

Affiliations

¹ Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
² First Affiliated Hospital of Army Medical University, Chongqing 400038, China.
³ Department of Traditional Chinese Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
⁴ TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
⁵ Department of Anorectal, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
⁶ Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.

Abstract

Diabetes mellitus (DM) is a chronic noninfectious disease that is mainly featured by pancreatic β-cell (β-cell) dysfunction and impaired glucose homeostasis. Currently, the pathogenesis of dysfunction of the β-cells in DM remains unclear, and therapeutic approaches to it are limited. Emodin (EMD), a natural anthraquinone derivative, has been preliminarily proven to show antidiabetic effects. However, the underlying mechanism of EMD on β-cells still needs to be elucidated. In this study, we investigated the protective effects of EMD on the high glucose (50 mM)-induced INS-1 cell line and the underlying mechanism. INS-1 cells were treated with EMD (5, 10, and 20 μM) when exposed to high glucose. The effects of EMD were examined by using the inverted phase-contrast microscope, qRT-PCR, ELISA, and western blot. The results showed that EMD could alleviate cellular morphological changes, suppress IL-1β and LDH release, and promote insulin secretion in high-glucose-induced INS-1 cells. Furthermore, EMD inhibits NOD-like receptor protein 3 (NLRP3) activation and gasdermin D (GSDMD) cleavage to alleviate pyroptosis induced by high glucose. Overexpression of NLRP3 reversed the above changes caused by EMD. Collectively, our findings suggest that EMD attenuates high-glucose-induced β-cell pyroptosis by inhibiting NLRP3/GSDMD signaling.