Zhuhuang Granules alleviate psoriatic inflammation via restoring gut microbiota balance and enhancing intestinal barrier integrity.

Psoriasis is a chronic inflammatory skin disorder characterized by excessive keratinocyte proliferation, immune dysregulation, and systemic inflammation. Emerging evidences highlight the gut-skin axis as a key regulatory mechanism linking gut microbiota dysbiosis to psoriasis pathogenesis. This study investigates the therapeutic effects of Zhuhuang Granules (ZH) on psoriasis, focusing on cutaneous inflammation, intestinal barrier integrity, and gut microbiota homeostasis. Using an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, ZH treatment significantly reduced Psoriasis Area and Severity Index (PASI) scores, epidermal hyperplasia, and inflammatory infiltration, with marked improvements observed following medium- and high-dose ZH treatment. ZH also suppressed systemic immune activation by decreasing spleen weight, inhibiting keratinocyte proliferation, and downregulating pro-inflammatory cytokines, including IL-22, IL-1β, TNF-α and CCL20. Additionally, ZH enhanced intestinal barrier function through the upregulation of essential tight junction proteins (TJP1, Occludin, and Claudin-1), leading to reduced intestinal permeability and systemic endotoxemia. 16S rRNA sequencing revealed that ZH partially reversed IMQ-induced gut dysbiosis, with partial restoration of several IMQ-associated microbial taxa, including Lachnospiraceae FCS020 group, Lachnospiraceae UCG-001, and Bacteroides. Functional prediction analysis indicated that ZH altered the predicted abundance of microbial functional pathways related to immune regulation and lipid metabolism. Importantly, antibiotic-mediated gut microbiota depletion attenuated the protective effects of ZH against IMQ-induced psoriasis-like inflammation, providing functional evidence for a contribution of the gut microbiota to the therapeutic effects of ZH. These findings suggest that ZH alleviates psoriasis-like inflammation through suppressing systemic inflammation, improved intestinal barrier functions, and microbiota restoration, supporting its therapeutic potential in psoriasis management.