Phytochemicals From Hansenia weberbaueriana for Psoriasis and Inflammatory Bowel Disease Comorbidity: Based on Network Pharmacology and In Vitro Analysis.

Abstract

Comorbidities, associated with higher rates of disability and mortality, have emerged as a global focus and a significant challenge. Psoriasis (PSO) and inflammatory bowel disease (IBD) are autoimmune disorders with frequent comorbidity and shared inflammatory pathways, yet targeted therapies remain limited. Utilizing an integrated approach combining network pharmacology, bioinformatics, machine learning, molecular docking, and in vitro experiments, we investigated Hansenia weberbaueriana (HW) for its potential to treat the comorbidity of PSO and IBD. Bioinformatics analysis identified 38 intersecting genes between PSO-IBD comorbidity and HW, predominantly enriched in the advanced glycation end-product (AGE)-receptor for AGE (RAGE) signaling pathway. Combining machine learning, weighted gene co-expression network analysis, and molecular docking prioritized PTGS2 (Cyclooxygenase 2 [COX2]) as the top target, with Cnidilin (HW8), a bioactive coumarin derivative from HW, exhibiting high-affinity binding (binding energy: -6.418 kcal/mol and molecular mechanics-generalized born surface area: -35.43 kcal/mol). Furthermore, 100-ns molecular dynamics (MD) simulations confirmed stable Cnidilin-PTGS2 interactions (root mean square deviation ∼2.3 Å). In vitro analysis demonstrated that Cnidilin (10 µM) significantly suppressed COX2, tumor necrosis factor-alpha, and nitric oxide in RAW 264.7 cells, supporting its multi-target mechanism. This study provided the first evidence supporting the therapeutic role of HW in PSO-IBD comorbidity via COX2 suppression and established a machine learning-driven framework for identifying natural compounds with dual therapeutic potential.