Structure-affinity driven repurposing of natural compounds and herbal prescriptions for ulcerative colitis and psoriasis.

Background: Psoriasis and ulcerative colitis (UC) are immune-mediated chronic inflammatory diseases that affect barrier organs and share significant overlap in both pathogenesis and treatment strategies. Although the advent of biologics has transformed therapeutic options, their high cost often limits long-term accessibility, underscoring the need for alternative approaches.

Purpose: Natural compounds and traditional medicine represent valuable sources for novel drug discovery and repurposing, but systematic strategies for repurposing traditional medicines remain underdeveloped.

Methods: Here, we present a computational framework for drug repurposing based on drug-target affinity and structural rationality, focused on the traditional herbs and prescriptions of JAK family and chemokine receptors.

Results: We identified 204 natural compounds, among which 9-hydroxycamptothecin showed the most promising therapeutic potential for both psoriasis and UC. Notably, WU MEI PILL, a classical prescription in East Asian traditional medicine, also emerged as a promising multi-target therapy for both diseases. In vivo experiments confirmed that 9-hydroxycamptothecin and WU MEI PILL significantly alleviated disease symptoms, improved intestinal mucosal and epidermal pathologies, and upregulated intestinal Claudin-1 and MUC-2 expression. These effects were mediated through suppression of JAK1/STAT3 phosphorylation.

Conclusion: This study introduces a tailored approach for traditional medicine-based drug repurposing, offering a scalable and efficient strategy for identifying natural therapeutics and guiding clinical decision-making, modernization, and standardization of traditional medicine.