2. Academic Validation
  3. Celastrol induces premature ovarian insufficiency by inducing apoptosis in granulosa cells

Celastrol induces premature ovarian insufficiency by inducing apoptosis in granulosa cells

  • Biomed Pharmacother. 2023 Nov 11:169:115815. doi: 10.1016/j.biopha.2023.115815.
Fan Wen 1,  Dandan Liu 2,  Mingming Wang 3,  Shujie Zhang 2,  Wenhua Kuang 2,  Lixia Yuan 4,  Jigang Wang 5,  Gang Liu 6
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, Shunde Hospital of Southern Medical University, Foshan 528000, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 2 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 3 Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
  • 4 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China. Electronic address: cnylxtcm@163.com.
  • 5 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Nephrology, Shenzhen key Laboratory of Kidney Diseases, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518020, China; Department of Oncology, the Affiliated Hospital of Southwest Medical University, China. Electronic address: jgwang@icmm.ac.cn.
  • 6 Department of Rehabilitation Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: lg2781@smu.edu.cn.
PMID: 37956480 DOI: 10.1016/j.biopha.2023.115815
Abstract

Celastrol, a natural compound purified from the Chinese herb Tripterygium wilfordii Hook. f., has excellent pharmacological activity for the treatment of various diseases. Assessing the safety of its use is essential for its development into a clinical medicine. However, research assessing its toxicity on the female reproductive system has never been reported. In this study, the ovarian toxicity of celastrol and its underlying mechanism were investigated. We found that celastrol induced premature ovarian insufficiency and Apoptosis in granulosa cells. Activity-based protein profiling results showed that high mobility group box 1 was a candidate target protein of celastrol. Celastrol directly bound to Cys106 of high mobility group box 1. Knocking down high mobility group box 1 induced Apoptosis of granulosa cells, while overexpression of this gene reversed celastrol-induced Apoptosis. Celastrol treatment upregulated p21 transcription, but overexpression of high mobility group box 1 reversed this upregulation. Thus, Celastrol induces premature ovarian insufficiency and Apoptosis in granulosa cells by directly binding to high mobility group box 1 and interfering with its biological function to regulate p21 transcription. This study provides valuable information for assessing the safety of the clinical application of celastrol on female patients.

Keywords

Activity-based protein profiling; Apoptosis; Celastrol; Granulosa cell; Premature ovarian insufficiency.

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