In silico Analysis of the Anti-Pruritic Immunomodulatory Mechanisms of Chunwangbosim-dan Components Using Network Pharmacology and Molecular Docking 2333658

Abstract

Abstract Introduction Chronic pruritus is associated with chronic inflammatory skin diseases and is often non-histamine-dependent, involving immune dysregulation and inflammatory signaling. Conventional antihistamine-based therapies often show limited efficacy, emphasizing the need for alternative approaches targeting upstream immune and inflammatory pathways. Chunwangbosim-dan (CWBSD) is a traditional East Asian herbal prescription. Among its components, Coptidis Rhizoma (CR) and Rehmanniae Radix (RR) were selected based on reproducible anti-inflammatory activity. We investigated their potential anti-pruritic effects using an in silico approach. Methods Compounds of CR and RR were identified from the TCMSP and TCMID, and their putative targets were predicted using SwissTargetPrediction. Pruritus-related genes were collected from GeneCards, OMIM, and TTD. Overlapping targets were used to construct PPI networks via STRING and h Cytoscape (Degree and MCC) to define hub genes. GO and KEGG enrichment analyses were performed using STRING. Molecular docking simulations were conducted using AutoDock Vina to evaluate binding affinities between representative compounds and key hub proteins. Results Network pharmacology analysis revealed that the selected components of CWBSD interacted with multiple pruritus-associated immune targets and were significantly enriched in inflammatory and immune signaling pathways, including MAPK, PI3K-Akt, JAK-STAT, IL-17, and chemokine signaling pathways. Molecular docking demonstrated strong and stable binding interactions between coptisine from CR and key signaling mediators such as AKT1, JAK2, and EGFR. In addition, isoacetoside from RR exhibited favorable binding affinities with MAPK family proteins, supporting their potential role in modulating inflammatory signal transduction. Conclusion CR and RR may modulate pruritus-relevant immune signaling through multi-target, multi-pathway actions, supporting experimental validation of CWBSD as a complementary strategy for chronic pruritus. Funding Source Portions of this work was carried out within the Korea Institute of Oriental Medicine, (grant number KSN18384113). Topic Categories Computational and Systems Immunology (COMP)