Isoliquiritigenin alleviates abnormal endoplasmic reticulum stress induced by type 2 diabetes mellitus
10.16438/j.0513-4870.2024-0867
- VernacularTitle:异甘草素改善2型糖尿病所致异常内质网应激机制研究
- Author:
Kai-yi LAI
1
;
Wen-wen DING
1
;
Jia-yu ZHANG
1
;
Xiao-xue YANG
1
;
Wen-bo GAO
1
;
Yao XIAO
2
;
Ying LIU
1
Author Information
1. School of Life Sciences, Beijing University of Chinese Medicine, Beijing
2. School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing
- Publication Type:Research Article
- Keywords:
isoliquiritigenin;
type 2 diabetes mellitus;
endoplasmic reticulum stress;
insulin sensitivity;
glucose metabolism
- From:
Acta Pharmaceutica Sinica
2025;60(1):130-140
- CountryChina
- Language:Chinese
-
Abstract:
Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.
