Curcumin alleviates depression-aggravated psoriasis by targeting MMP9-regulated apoptotic pathways

Depression and psoriasis are highly comorbid, yet their shared molecular mechanisms remain poorly understood. Utilizing cross-sectional data from NHANES and Mendelian randomization (MR), a significant association and causal link between depression and psoriasis were established. A combined mouse model of chronic unpredictable mild stress (CUMS) and imiquimod-induced psoriasis confirmed that depressive state exacerbates psoriasis-like skin lesions. Integrated multi-omics analyses (including bulk and single-cell RNA sequencing, machine learning, and eQTL/pQTL-MR) identified apoptosis as a key shared pathway, with matrix metallopeptidase 9 (MMP9) as a central causal gene. Animal experiments confirmed MMP9 upregulation in both skin and brain tissues. Molecular docking predicted strong binding of curcumin to MMP9, and subsequent in vivo intervention demonstrated that curcumin downregulated MMP9 expression and alleviated both pathological conditions. These findings reveal MMP9-mediated apoptosis as a central pathological link in the comorbidity of depression and psoriasis and suggest a dual-treatment strategy for this comorbidity.