Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model

Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns.This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity.A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration's Liver Toxicity Knowledge Base (LTKB).Eleven herbal ingredients with proven liver toxicity in the literature were added into the dataset besides chemicals from LTKB. The finally generated QSAR model yielded a sensitivity of 83.8%, a specificity of 70.1%, and an accuracy of 80.2%. Among the externally tested 20 ingredients from TCMs, 14 hepatotoxic ingredients were all accurately identified by the QSAR model derived from the dataset containing natural hepatotoxins.Adding natural hepatotoxins into the dataset makes the QSAR model more applicable for TCM hepatotoxicity assessment, which provides a right direction in the methodology study for TCM safety evaluation. The generated QSAR model has the practical value to prioritize the hepatotoxicity risk of TCM compounds. Furthermore, an open-access international specialized database on TCM hepatotoxicity should be quickly established.