Jaungo-based herbal complex regulates psoriasis-associated macrophage–keratinocyte inflammatory axis

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Background/Objectives: Psoriasis is a chronic inflammatory skin disease characterized by dysregulated cross-talk between macrophages and keratinocytes, resulting in excessive cytokine signaling and impaired epidermal barrier function. Traditional Jaungo has long been used as a topical remedy for inflammatory skin disorders, and its core herbal components exhibit well-documented anti-inflammatory and tissue-protective properties. This study aimed to develop a Jaungo-based herbal complex (JBHC) and evaluate its effects on macrophage-mediated inflammatory responses and keratinocyte barrier dysfunction under psoriasis-like conditions. Methods: Publicly available transcriptomic datasets were analyzed to identify inflammatory and barrier-related gene expression patterns in psoriatic lesions. The anti-inflammatory effects of JBHC were assessed in LPS-stimulated RAW264.7 macrophages by analyzing the expression of inflammatory mediators and signaling pathways. To evaluate macrophage-keratinocyte cross-talk, conditioned media from activated macrophages, with or without JBHC treatment, were applied to keratinocytes, followed by analysis of epidermal barrier gene expression. Results: Transcriptomic analyses revealed consistent upregulation of inflammatory cytokines and chemokines, accompanied by significant suppression of key epidermal barrier genes in psoriatic lesions. JBHC markedly attenuated LPS-induced inflammatory signaling in RAW264.7 macrophages by downregulating NOS2, PTGS2, and multiple cytokine genes, while selectively modulating STAT1/STAT3 activation. Conditioned media from activated macrophages significantly suppressed the expression of filaggrin (FLG) and loricrin (LOR) in keratinocytes; however, conditioned media from JBHC-treated macrophages effectively mitigated this barrier gene suppression. Conclusion: JBHC modulates macrophage-mediated inflammatory pathways and protects keratinocyte barrier gene expression under psoriasis-like inflammatory conditions. These findings suggest that JBHC has potential as a functional herbal complex targeting the macrophage-keratinocyte inflammatory axis in chronic inflammatory skin diseases such as psoriasis.