A modified Heat-Clearing and Blood-Cooling Chinese herbal formulation targeting multiple key machanistic molecules in the treatment of imiquimod-induced psoriasis mouse model

Background and Purpose: The Xijiao Dihuang Decoction demonstrates therapeutic potential for psoriasis with heat-blood patterns. This study investigated the efficacy of its modified formulation, the Heat-Clearing and Blood-Cooling(HCBC) recipe, in an imiquimod (IMQ)-induced psoriasis mouse model,as well as screening its active components involved in the pharmaco-mechanism of action. Experimental Approach:A psoriasis-like dermatitis model was established using IMQ. Serum metabolites of HCBC were identified via UPLC-QE-MS. Network pharmacology predicted target genes and pathways, which were visualized via protein-protein interaction networks and validated by molecular docking. The therapeutic effects and predicted mechanisms were empirically confirmed through phenotypic assessment, histology (H&E, IHC, mIHC), RT-PCR, ELISA, and flow cytometry. Key Results: 43 differential HCBC metabolites were identified in the serum. Network analysis revealed 35 intersection targets between active components and psoriasis, with TNF, IL-10, Stat3, IFN-r, and VEGF as potential key targets for psoriasis therapy. KEGG enrichment analysis revealed that the intersecting targets participate in several key pathways, including T cell receptor signaling, JAK-STAT3, Th17 cell differentiation, and IL-17 signaling. Molecular docking demonstrated that TNF and STAT3, as key targets, exhibited favorable docking interactions with active ingredients, such as myricetin and sesamin. In comparison to the untreated IMQ group, the HCBC Recipe significantly alleviated clinical symptoms, curbed pro-inflammatory mediator generation, and blocked Th1 and Th17 cell specialization. Notably, the RORγt+FOXP3+CD4T cells were detected in the IMQ-induced and HCBC treated lesions. Conclusion and Implications: This study characterized the key active components of the modified HCBC formulation, highlighting its holistic role in the management of psoriasis by targeting multiple pathways, such as JAK-Stat, Th17-IL-17A. HCBC modulated T cell immunity and the release of pro-inflammatory factors.