Discovery of ergosterol derivative from Aspergillus sp. TJ507 that protects against hepatic ischemia/reperfusion injury

Hong Hu; Yanhui Li; Zhengyi Shi; Xiangli Zhao; Xueqi Lan; Meng Wu; Bo Tao; Yeting Zhang; Xinye Huang; Pengfei Bu; Yi Guo; Xiaosheng Tan; Changxing Qi; Yonghui Zhang

doi:10.1016/j.bioorg.2023.106530

Discovery of ergosterol derivative from Aspergillus sp. TJ507 that protects against hepatic ischemia/reperfusion injury

Bioorg Chem. 2023 Jun:135:106530. doi: 10.1016/j.bioorg.2023.106530. Epub 2023 Apr 8.

Authors

Hong Hu¹, Yanhui Li², Zhengyi Shi¹, Xiangli Zhao³, Xueqi Lan¹, Meng Wu³, Bo Tao¹, Yeting Zhang¹, Xinye Huang¹, Pengfei Bu¹, Yi Guo¹, Xiaosheng Tan⁴, Changxing Qi⁵, Yonghui Zhang⁶

Affiliations

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China.
² Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
³ Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, Hubei Province, People's Republic of China.
⁴ Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address: txs900416@163.com.
⁵ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address: qichangxing@hust.edu.cn.
⁶ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. Electronic address: zhangyh@mails.tjmu.edu.cn.

PMID: 37054517
DOI: 10.1016/j.bioorg.2023.106530

Abstract

Hepatic ischemia/reperfusion injury is a major cause of hypohepatia after surgical procedures such as hypovolemic shock, transplantation, and so on. In our continuous study of bioactive natural products from fungus, eight ergosterol-type sterides (1-8), including two undescribed compounds, sterolaspers A (1) and B (2), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and comparison with the reported NMR data as well as X-Ray single crystal diffraction tests. Activity screen of these isolates showed 5α-stigmast-3,6-dione (3) possessing anti-hypoxia injury effects against CoCl₂-induced hypoxia damage in hepatocytes. More importantly, compound 3 could improve liver function, alleviate liver damage, and restrain the hepatocellular apoptosis in hepatic ischemia/reperfusion injury murine model. As such, this ergosterol-type steride, 5α-stigmast-3,6-dione (3), might serve as lead structure for the development of novel hepatoprotective agents in the clinical treatment of hepatic ischemia/reperfusion injury.

Keywords: Anti-hypoxia injury activities; Aspergillus sp.; Hepatic ischemia/reperfusion injury; Sterides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Aspergillus
Hepatocytes
Ischemia / complications
Liver*
Mice
Reperfusion Injury* / drug therapy