Simultaneously screening multiple UGT1A1 inhibitors from Polygonum multiflorum root using ultrafiltration LC–MS |
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Authors: | Yan Jiang Cai Zhang Xian Zheng Zhen Zhao Hui-Jun Li |
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Affiliation: | 1. College of Chemical Engineering, Nanjing Forestry University, Nanjing, China;2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China |
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Abstract: | Liver injury induced by Polygonum multiflorum root (PMR) is an immediate issue requiring global attention. UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors are suspected to additively contribute to the hepatotoxicity of PMR. This study was deliberately designed to simultaneously screen UGT1A1 inhibitors from PMR, and their co-contribution to hepatotoxicity was determined. Using ultrafiltration coupled to LC–MS method, four compounds, namely cis-2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside, trans-2,3,5,4′-tetrahydroxystilbene-2-O-β-d -glucoside, emodin-8-O-β-d -glucoside, and emodin, were screened, exhibiting the in vitro inhibitory activities against UGT1A1 with IC50 values of 76.23, 18.70, 62.18, and 34.02 μM, respectively. The varying activities of the screened UGT1A1 inhibitors were demonstrated by performing a molecular docking simulation. Finally, zebrafish larvae and mice assays demonstrated that the UGT1A1 inhibitors co-contributed to the hepatotoxicity of PMR. These findings are conducive to understand the role of UGT1A1 inhibitors in PMR-induced hepatotoxicity. |
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Keywords: | hepatotoxicity Polygonum multiflorum root UDP-glucuronosyltransferase 1A1 inhibitor ultrafiltration zebrafish |
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