AR and ITGAL: Key Mediators of Andrographis paniculata's Anti-Psoriatic Effects Revealed by Multi-Omics Analysis

This study analyzed the mechanisms of action of Andrographis paniculata (AP), a medicinal plant with diverse pharmacological properties, on psoriasis.

The active components of AP and their corresponding targets were identified. These targets were subsequently intersected with differentially expressed genes (DEGs) and immune-related genes associated with psoriasis. The resulting gene set was subjected to functional enrichment analysis and immune infiltration analysis. The scRNA-seq data were analyzed to delineate the single-cell landscape in psoriasis and cell type-specific expression of genes of interest. Further, the molecular docking and experimental verification were performed for validation.

Active components of AP and their targets were predicted. Cross-referencing these targets with psoriasis DEGs revealed 2 feature genes (AR and ITGAL), both exhibiting strong diagnostic potential. The two genes were associated with differentially enriched pathways and immune cell infiltration. Further, scRNA-seq analysis identified 10 cell subclusters. Notably, AR was expressed in reticular fibroblasts of healthy controls, while ITGAL was expressed in T cells of psoriasis samples. Molecular docking confirmed a stable binding interaction between Dehydroandrographolide and AR. In vitro validation using an M5 cytokine-induced keratinocyte model demonstrated that Dehydroandrographolide exerted potent anti-inflammatory and antiproliferative effects. Furthermore, it significantly modulated the protein expression levels of both genes.

Combining in-silico and in-vitro analyses, this study identified AR and ITGAL as potential key mediators and validated the efficacy of the active component of AP, Dehydroandrographolide, against psoriasis.

Collectively, the study demonstrated that AP had the potential anti-psoriasis effects.