Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action. BALB/c mice were administered topical imiquimod to induce psoriasis-like skin and were then randomly assigned to control, vehicle control, salvianolic acid B in vehicles, and 0.25% desoximetasone ointment treatment groups. Barrier function, cytokine expression, histology assessment, and disease severity were evaluated. The results showed that salvianolic acid B-containing microemulsion alleviated disease severity, reduced acanthosis, and inhibited interleukin-23/interleukin-17 (IL-23/IL-17) cytokines, epidermal proliferation, and increased skin hydration. Our study suggests that salvianolic acid B represents a possible new therapeutic drug for the treatment of psoriasis. In addition, such formulation could obtain high therapeutic efficacy in addition to providing sufficient hydration for dry skin.

(1) Background: Psoriasis is a T helper 1/T helper 17 cells-involved immune-mediated genetic disease. Lithospermic acid, one of the major phenolic acid compounds of Danshen, has antioxidation and anti-inflammation abilities. Due to the inappropriate molecular weight for topical penetration through the stratum corneum, lithospermic acid was loaded into the well-developed microemulsion delivery system for IMQ-induced psoriasis-like dermatitis treatment. (2) Methods: BALB/c mice were administered with topical imiquimod to induce psoriasis-like dermatitis. Skin barrier function, disease severity, histology assessment, autophagy-related protein expression, and skin and spleen cytokine expression were evaluated. (3) Results: The morphology, histopathology, and skin barrier function results showed that 0.1% lithospermic acid treatment ameliorated the IMQ-induced psoriasis-like dermatitis and restored the skin barrier function. The cytokines array results confirmed that 0.1% lithospermic acid treatment inhibited the cutaneous T helper-17/Interleukin-23 axis related cytokines cascades. (4) Conclusions: The results implied that lithospermic acid might represent a possible new therapeutic agent for psoriasis treatment.

Skin barrier dysfunction plays a pivotal role in the pathogenesis of inflammatory skin diseases such as atopic dermatitis and psoriasis. This review provides a comprehensive analysis of recent advances in the transcriptional and post-transcriptional regulation of key skin barrier-related genes, including FLG, LOR, CLDN1, AQP3 and IVL. We detail how intrinsic genetic variations and immune-mediated cytokine pathways-particularly the T helper 2 and T helper 17 axes-disrupt the epidermal defense system. Emerging therapeutic strategies targeting skin barrier restoration through natural compounds, biologic agents, and gene modulation technologies-such as small interfering RNA, antisense oligonucleotides, and histone deacetylase inhibitors-are critically reviewed. Moreover, the impact of the gut-skin axis and microbial metabolites on epidermal gene expression is discussed. Finally, we highlight the role of artificial intelligence and multi-omic integration in driving biomarker discovery and enabling precision dermatology. These insights underscore the potential of barrier-centric, gene-targeted approaches as a transformative strategy in managing chronic dermatoses.

Sakuranetin, a methoxylated flavanone with known anti-inflammatory and antioxidant properties, has yet to be explored for its therapeutic potential in psoriasis treatment. This study evaluates its efficacy in an imiquimod-induced psoriasis-like murine model, focusing on both immune modulation and skin barrier restoration. Topical administration of sakuranetin significantly attenuated psoriatic inflammation, with high-dose treatment achieving comparable efficacy to desoximetasone. RNA sequencing and qPCR validation revealed that sakuranetin modulates keratinization, cornified envelope formation, and kallikrein-related peptidase activity, suggesting its role in epidermal homeostasis. Notably, sakuranetin selectively downregulated IL-17A while maintaining IL-17F expression, supporting a targeted immunomodulatory effect. Additionally, sakuranetin upregulated KRT1, KRT16, KLK7, Sprr2f, and Wfdc18 while downregulating Sprr2k and Sprr3, indicating a refined regulation of skin barrier proteins. The observed upregulation of Tslp suggests a potential role in epidermal repair mechanisms. These findings highlight sakuranetin as a novel, plant-derived therapeutic candidate with dual anti-inflammatory and skin barrier-enhancing properties, providing a potential corticosteroid-sparing approach for long-term psoriasis management.

(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01–0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg/gm clobetasol ointment. (4) Conclusions: The cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.

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