The Material Basis for the Beneficial Effects of Paidu Powder on Hyperuricemia: A Network Pharmacology and Clinical Study

Background: Paidu powder (PDP) is a formula that is used in traditional Chinese medicine (TCM) practices and has been demonstrated to be effective to lower blood uric acid (UA) level. Methods: Network pharmacology was employed to probe the mechanistic basis for the beneficial effects of PDP. Then, PDP was subjected to Aspergillus oryza AS3.042 fermentation, and the primary bioactive compounds in the resultant samples were analyzed via HPLC. A clinical study was then performed to test the therapeutic effects of unfermented and fermented PDP on HUA. Results: Network pharmacology strategies identified 122 active compounds and 924 HUA‐related target genes, with 61 overlapping targets relative to PDP and HUA ultimately being selected. These target genes were associated with 474 GO biological process terms and 136 KEGG pathways. Moreover, good binding was observed between three main bioactive compounds of interest and nine primary target proteins. Notably, the levels of the top three bioactive compounds (quercetin, kaempferol, and naringenin) were significantly elevated by 308.96%, 1386.44%, and 719.21%, respectively, following fermentation. Clinical analyses indicated that both PDP and fermented PDP treatment significantly reduced UA, CRE, and BUN levels ( p < 0.01), with a higher overall efficacy rate in the fermented PDP group relative to the unfermented PDP group ( p < 0.01). Fewer adverse reactions were also observed in the fermented PDP group. Conclusion: These results offer novel insights into the putative mechanisms through which PDP can exert its beneficial effects against HUA, offering a novel basis for the identification of the pharmacological effects of this popular TCM prescription.