Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress  

作　　者：Qian-zhuo Liu Hui Han Xin-ru Fang Lu-yao Wang Dan Zhao Miao-zhu Yin Nian Zhang Peng-yu Jiang Zhi-hui Ji Li-min Wu 

机构地区：[1]Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,Anhui Province,China [2]Center for Reproduction and Genetics,the First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230031,Anhui Province,China

出　　处：《Journal of Integrative Medicine》2024年第4期493-502,共10页结合医学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (No. 82374212, No. 81971446 and No. 81673811);the Clinical Special Translational Project of the Anhui Provincial Science and Technology Department (No. 202204295107020044);the Key Project of the Anhui Provincial Department of Education (No. 2022AH050523)。

摘　　要：Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD.Methods:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress.Results:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway.Conclusion:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

关 键 词：BERBERINE Hepatolenticular degeneration Copper deposition Ferroptosis Endoplasmic reticulum stress 

分 类 号：R285.5[医药卫生—中药学]