Planta Med 2023; 89(03): 254-261
DOI: 10.1055/a-1939-7417
Biological and Pharmacological Activity
Original Papers

Berberine Regulates GPX4 to Inhibit Ferroptosis of Islet β Cells

Lei Bao
Department of Endocrinology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
Yixuan Jin
Department of Endocrinology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
Jiani Han
Department of Endocrinology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
Wanqiu Wang
Department of Endocrinology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
Lingling Qian
Department of Endocrinology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
Department of Endocrinology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu Province, China
› Author Affiliations


Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used to treat diabetes. Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways. However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet β cells in T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet β cell viability and proliferation by MTT and colony formation assays. Western blot and qRT-PCR were utilized to examine GPX4 expression in islet β cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet β cells was investigated by evaluating the content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to inhibit ferroptosis of islet β cells was further revealed by the rescue experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate cell viability and the proliferative abilities of islet β cells. Moreover, BBR stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet β cells, which functioned similarly as ferroptosis inhibitor Fer-1. In conclusion, BBR suppressed ferroptosis of islet β cells via promoting GPX4 expression, providing new insights into the mechanism of BBR for islet β cells.

Supporting Information

Publication History

Received: 25 February 2022

Accepted after revision: 15 August 2022

Article published online:
09 November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
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