Metabolic activation mediated genotoxicity of specific traditional Chinese medicine components

ZHANG Kai; WANG Xiaojuan; GE Guangbo; XIAO Xiaohe; WANG Yikun

doi:10.13506/j.cnki.jpr.2025.10.010

Abstract：Toxicity of traditional Chinese medicine(TCM)is a key issue restricting the modernization and internation-alization of TCM.The adverse events represented by nephrotoxicity and genotoxicity of Aristolochia sinensis have sounded the alarm for the safety of Chinese medicines.Genotoxicity of Chinese medicines is characterized difficulty in detection and iden-tification.Drug metabolism closely regulates the transformation and toxicity of TCM components.This review compiled the knowledge about metabolic activation in the genotoxicity of certain specific TCM components and natural products,summa-rized the pathways and patterns of metabolism-induced genotoxicity of TCM components,and highlighted the recent findings on genotoxicity biomarkers and genotoxicity mechanisms.Based on the existing literature,we found that metabolic activation is the key to the toxicity of TCM components,and genotoxic substances is not the prototypes of TCM ingredients,but the re-active metabolites produced after metabolic activation.Reactive metabolites are essentially terminal carcinogens that cova-lently bind to and damage DNA,causing mutations in proto-oncogenes or oncogenes,blocking the repair of DNA damage,and inducing tumorigenesis.In addition,this review also described the herbal components-DNA adducts and DNA mutational fingerprints,which provide biological biomarker references for risk control and translational studies of genotoxicity of herbal medicines and contribute to monitor and prevent the genotoxic effects of these components in further clinical practice.