Ferulic acid prevents Diosbulbin B-induced liver injury by inhibiting covalent modifications on proteins

Huiling Chen; Chenchen Liu; Meng Li; Yida Zhang; Zhendong Wang; Qiyao Jiang; Jianxin Wang; Qi Wang; Yue Zhuo

doi:10.1016/j.dmpk.2023.100507

Ferulic acid prevents Diosbulbin B-induced liver injury by inhibiting covalent modifications on proteins

Drug Metab Pharmacokinet. 2023 Jun:50:100507. doi: 10.1016/j.dmpk.2023.100507. Epub 2023 Mar 30.

Authors

Huiling Chen¹, Chenchen Liu¹, Meng Li², Yida Zhang³, Zhendong Wang¹, Qiyao Jiang¹, Jianxin Wang⁴, Qi Wang⁵, Yue Zhuo⁶

Affiliations

¹ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
² Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510405, China.
³ Department of Allergy and Clinical Immunology, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510405, China.
⁴ Department of Pharmaceutics, School of Pharmacy, Ministry of Education, Fudan University & Key Laboratory of Smart Drug Delivery, Shanghai, 201203, China.
⁵ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: wangqi@gzucm.edu.cn.
⁶ Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: zhuoyue@gzucm.edu.cn.

PMID: 37075616
DOI: 10.1016/j.dmpk.2023.100507

Abstract

Diosbulbin B (DIOB) has been reported to cause serious liver injury. However, in traditional medicine, DIOB-containing herbs are highly safe in combination with ferulic acid (FA)-containing herbs, suggesting potential neutralizing effect of FA on the toxicity of DIOB. DIOB can be metabolized to generate reactive metabolites (RMs), which can covalently bind to proteins and lead to hepatoxicity. In the present study, the quantitative method was firstly established for investigating the correlation between DIOB RM-protein adducts (DRPAs) and hepatotoxicity. Then, we estimated the detoxication effect of FA in combination with DIOB and revealed the underlying mechanism. Our data indicated that the content of DRPAs positively correlate with the severity of hepatotoxicity. Meanwhile, FA is able to reduce the metabolic rate of DIOB in vitro. Moreover, FA suppressed the production of DRPAs and decreased the serum alanine/aspartate aminotransferase (ALT/AST) levels elevated by DIOB in vivo. Thus, FA can ameliorate DIOB-induced liver injury through reducing the production of DRPAs.

Keywords: Diosbulbin B; Ferulic acid; Hepatoxicity; Protein adducts; Reactive metabolites.

MeSH terms

Chemical and Drug Induced Liver Injury* / metabolism
Chemical and Drug Induced Liver Injury* / prevention & control
Chemical and Drug Induced Liver Injury, Chronic* / metabolism
Drug-Related Side Effects and Adverse Reactions* / metabolism
Humans
Liver / metabolism
Proteins / metabolism

Substances

diosbulbin B
ferulic acid
Proteins