Enhancement of The Anti-Hyperuricemic Activity of Modified Simiao Wan by Optimizing The Conditions of Extraction of The Active Compounds, Using Network Pharmacology Approach

The objective of this study was to enhance the anti-hyperuricemic activity of modified Simiao wan (MSW) by optimizing the conditions of extraction of the active group of compounds determined from network pharmacology analysis. The main group of compounds involved in the uric acid lowering effect of MSW was identified based on the herb-compound-target network. After that, the optimal conditions of extraction of these compounds from MSW were determined using response surface methodology. Then, the biological effects of MSW extracted at optimal conditions and sub-optimal conditions were evaluated. The binding mode of the key compounds of MSW with the potent target was also explored using molecular docking and molecular dynamics. The results suggested that flavonoids, particularly quercetin, luteolin, kaempferol, and wogonin, might be important compounds involved in the anti-hyperuricemic activity of MSW. After that, the optimal conditions of extraction of flavonoid from MSW were determined, including ethanol concentration of 80% and time of extraction of 60 minutes. The results of the pharmacological assay indicated that MSW extracted at optimal conditions could significantly reduce uric acid levels compared with MSW extracted under sub-optimal conditions. The protein-protein interaction network, molecular docking, and molecular dynamics simulation showed that besides anti-hyperuricemic activity, flavonoids from MSW could also exhibit anti-inflammatory effects through inhibiting TNFα. Our study suggested that optimization of extraction based on network pharmacology analysis might be an effective approach to improve the therapeutic activity of this traditional medicine.