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

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

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Objective:Hepatolenticular degeneration(HLD)is an autosomal recessive disorder that manifests as mul-tiorgan 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 dam-age 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 pro-tein 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.

BerberineHepatolenticular degenerationCopper depositionFerroptosisEndoplasmic reticulum stress

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

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Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,Anhui Province,China

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

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaClinical Special Translational Project of the Anhui Provincial Science and Technology DepartmentKey Project of the Anhui Provincial Department of Education

8237421281971446816738112022042951070200442022AH050523

2024

10.1016/j.joim.2024.05.003

结合医学学报(英文版)
上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD
影响因子：0.711
ISSN：2095-4964
年,卷(期)：2024.22(4)