Kakuol and asarinin protecting liver injury via HSP90AA1/CDK2/mTOR signaling pathway

Ling Jiang; Cai-Bo Tian; Rui-Han Ye; Nian Shi; Xing-Chao He; Yun-Li Zhao; Xiao-Dong Luo

doi:10.1016/j.fitote.2024.106297

Kakuol and asarinin protecting liver injury via HSP90AA1/CDK2/mTOR signaling pathway

Fitoterapia. 2024 Nov 17:180:106297. doi: 10.1016/j.fitote.2024.106297. Online ahead of print.

Authors

Ling Jiang¹, Cai-Bo Tian¹, Rui-Han Ye¹, Nian Shi¹, Xing-Chao He¹, Yun-Li Zhao², Xiao-Dong Luo³

Affiliations

¹ Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
² Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: zhaoyunli@ynu.edu.cn.
³ Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address: xdluo@ynu.edu.cn.

PMID: 39551106
DOI: 10.1016/j.fitote.2024.106297

Abstract

Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro. In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.

Keywords: Asarinin; HSP90AA1/CDK2/mTOR pathway; Hepatoprotective effect; Kakuol; Network pharmacology.