AUTHOR=Kong Wei-Song , Zhou Gui , Xu Li-Wei , Wang Kun , Feng Yi-Ming , Tao Li-Yu , Xie Rui-Fang , Yang Ming , Zhou Xin TITLE=Beware of the Potential Risks for Polygoni Multiflori Caulis-Induced Liver Injury JOURNAL=Frontiers in Pharmacology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.868327 DOI=10.3389/fphar.2022.868327 ISSN=1663-9812 ABSTRACT=Background: Reynoutria multiflora (Thunb.) Moldenke (PM) is a widely-used medicinal plant in China whose root and stem are included in the Chinese Pharmacopoeia as Polygoni Multiflori Radix (RPM), Polygoni Multiflori Radix Preparata (PMP) and Polygoni Multiflori Caulis (PMC). The hepatotoxicity of RPM and PMP are concerned by public while the risk of PMC is ignored. Purpose: Here, we investigate the potential risks for PMC-induced liver injury from clinical, chemical and animal features. Study design: Firstly, we analyzed the 12-month usage of RPM, PMP and PMC in Longhua Hospital. Secondly, we determined the contents of gallic acid, cis-2,3,5,4’-tetrahydroxy-stilbene-2-O-β-D-glucoside (cis-SG), trans-2,3,5,4’-tetrahydroxy-stilbene-2-O-β-D-glucoside (trans-SG), emodin-8-O-β-D-glucoside (EG), physcion-8-O-β-D-glucoside (PG), emodin and physcion in the water extracts from 15 batches of RPM, PMP and PMC. Thirdly, we probed the hepatotoxic effect of RPM, PMP and PMC in mice and explored the mechanism of cis-SG and trans-SG causing the liver injury at the dosages based on our results from the first and second parts. Results: PMC had nearly five times amount of usage in both outpatient prescriptions and inpatient orders than RPM and PMP did. 68% dosage of PMC was 30 g. The contents of cis-SG, trans-SG and emodin in PMC water extracts were significantly lower than those in RPM and PMP water extracts. PMC induced milder idiosyncratic liver injury for its lower content of cis-SG and trans-SG than its root counterparts. Conclusion: The potential risks for PMC-induced liver injury should be fully aware of.