Investigation of the mechanism of action of simiao pill against gout using network pharmacology and experimental validation

Background: Gout is a chronic disease of deposition of monosodium urate crystals, characterised by hyperuricaemia and gouty arthritis, plaguing the whole world. Simiao Pill (SMP), a classic herbal formula, has been extensively used to treat arthritic symptoms in clinical practice in China for centuries. The action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of gout. However, the pharmacological mechanisms of SMP still remain vague to date.Hypothesis/Purpose: In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypouricemic mechanisms of SMP.Study design: At first, we collected putative targets of SMP based on Traditional Chinese Medicine Systems Pharmacology Database databases, and relevant targets of gout were summarised by four searching database, including Disgenet, therapeutic target database, Online Mendelian Inheritance in Man, and Gene Cards. The putative targets of SMP and known therapeutic targets of gout built an interaction network, so the networks of compound targets and disease-targets were obtained soon. Then, the protein-protein interactions analysis and molecular docking verification were established. Finally, the key genes were used to find the biological pathway and explain the therapeutic mechanism by genome ontology and kyoto encyclopaedia of genes and genomes analysis. Results: In our study, 30 hypouricemic components and 600 hypouricemic targets of SMP were filtrated based on an online network database. Then the component-target interaction network was constructed, 10 key components and 15 key targets were further obtained. Docking studies indicated that the bio-active compounds could stably bind the pockets of target proteins. Go enrichment and and kyoto encyclopaedia of Genes and genomes pathway analysis indicated that SMP had a strong integration with gout and hyperuricemia, which might significantly contribute to multiple therapeutic effect.Conclusions: In summary, this study used systems pharmacology to demonstrate the main components and mechanism of SMP in treating gout. Moreover, the work provided a scientific basis for the further effect research of SMP and its monomer components, but also provided a new therapeutic strategy in gout.