Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model

<b>Background:</b> Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns. <b>Objective:</b> This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity. <b>Methods:</b> 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). <b>Results:</b> 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. <b>Conclusions:</b> 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.