Abstract: Objective To establish a rapid method for screening hepatotoxic components in Polygonum multiflorum (P.M.) by taking the farnesoid X receptor (FXR) as the target. Methods First of all, computer molecular docking technology was adopted, Discovery Studio 2.5 software was used to molecularly dock the target compounds with the FXR, and the target compounds were screened virtually with FXR inhibitors as the reference objects. Next, the cell counting kit (CCK-8) method was used to investigate the toxicity of the target compounds on HepaRG after 24 h of treatment, while real-time PCR was used to determine the effects of the target compounds on the relative expression level of FXR genes in HepaRG cells. Results The molecular docking results showed that nine components in Polygonum multiflorum, including aloe-emodin-8-O-β-D-glucoside and emodin-8-O-β-D-glucoside, were potential inhibitors of FXR. In vitro cytotoxicity test further confirmed that both aloe-emodin-8-O-β-D-glucoside and emodin-8-O-β-D-glucoside had hepatotoxicity that could significantly inhibit the expression level of FXR genes. Conclusion This study effectively predicts the potential hepatotoxic components of Polygonum multiflorum, and a rapid and efficient high-throughput hepatoxicity screening method is established, which is expected to provide new ideas for safety evaluation of traditional Chinese medicine.

Key words: Polygonum multiflorum, farnesoid X receptor, molecular docking, hepatotoxicity, safety evaluation