Background This study used a holistic network pharmacological approach to clarify the mechanism of Compound Zeqi Granule (CZG) in treating psoriasis vulgaris (PV). Methods The potential bioactive compounds and corresponding targets of CZG were collected and searched via the TCMSP database. Disease targets of PV were obtained from the GeneCards database. The targets of CZG and PV were standardized by the UniProt database. GO and KEGG enrichment analyses were performed using the Metascape database. Then, molecular docking verification was conducted using the CB-Dock database. Animal experiments were conducted to validate the effects of CZG on PV. Results This approach identified 99 bioactive compounds, 579 potential drug targets, 822 PV-related targets, and 108 potential target proteins. The biological processes were primarily related to regulation of defense response, regulation of inflammatory responses, and cellular response to lipid. The targets of CZG for treating PV were significantly associated with 20 pathways including JAK-STAT signaling pathway. Animal experiments confirmed that CZG exerted its therapeutic effects on PV by promoting the expression of IL-10 and JUN, and inhibiting the activation of STAT1 and STAT3. Conclusion The present study provides evidence supporting the efficacy of CZG for the treatment of PV through a multi-compound, multi-target and multi-pathway approach and lays a theoretical foundation for further experimental research in this field.
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