Computational biomedical modeling and screening for prediction of molecular mechanisms of Simiao Pill against hyperuricemia

Hyperuricemia (HUA) is a type of purine metabolism disease and Simiao Pill (SMP), a classic herbal prescription, has a long history of treating HUA. Nonetheless, the mechanisms underlying SMP against HUA remain unclear. We employed computational biomedical modeling and screening to explore the potential pharmacodynamic components and the mechanisms of SMP for HUA. We obtained 6,045 docking results between 403 herbal compounds and 15 HUA-related targets (average binding affinity −7.081 kcal/mol). We identified 34 signaling pathways based on the 15 HUA-related proteins. Nitric-oxide synthase 3 (NOS3) was found to be the most promising drug target of SMP against HUA, exhibiting the best average binding affinity of −8.05 kcal/mol. Chelerythrine and quercetin were predicted to be the most bioactive compounds for xanthine dehydrogenase (XDH), a known drug target, along with kihadanin A and limonin for NOS3. Of all SMP compounds, prenol lipids, steroids and alkaloids were predicted to be the three primary classes of compounds with potential for targeting NOS3 and XDH. SMP may treat HUA by mechanisms that involve multi-targets and pathways. Our study presented a novel horizon for exploring the mechanism of SMP against HUA and developing potential drugs. Further experimental research is required to verify our results.