Discovery, evaluation, prevention, and control of liver injury risk by Polygoni Multiflori Radix

Abstract

In recent years, adverse reactions and events associated with traditional Chinese medicines (TCM) and herbal medicines (HM) have frequently occurred. In particular, with regard to the safety of newly discovered TCM that have been deemed “toxic,” providing a scientifically based answer and developing effective solutions is challenging. Owing to the complexity of TCM/HM products and lack of systematic research, our understanding of the potential causes of TCM/HM-induced liver injury is limited. Therefore, significant advancements in understanding the toxicity of TCM and preventing and managing safety risks are urgently needed to address the safety concerns associated with TCM/HM. Using Polygoni Multiflori Radix (PMR) hepatotoxicity as a typical example, we evaluated the “integrated evidence chain” based on the causality evaluation of TCM-induced liver injury, and confirmed the objective authenticity of PMR hepatotoxicity. Furthermore, we first proposed and established a disease-syndrome-combined toxicology model that was applied to the material basis and analysis of the mechanism of PMR-induced hepatotoxicity. The mechanism hypothesis of “three-factor-induced toxicity” of idiosyncratic hepatotoxicity of TCM was proposed and confirmed. Based on this, the disease characteristics of the population susceptible to PMR idiosyncratic hepatotoxicity were elucidated, and various biomarkers were screened and identified, including the genetic marker HLA-B*35:01 and immunological and metabolomic markers. Finally, the study explored and established a safe medication strategy and method for “host-drug-use” three-dimensional risk prevention and control based on identifying susceptible individuals, controlling susceptible substances, and clinical precision medication. This study provides a foundation for comprehensively understanding the scientific implications of TCM/HM toxic side reactions and establishing scientific and effective risk prevention and control strategies.