Integrative multi-omics, network pharmacology, and molecular simulation of herbal compounds targeting immune tolerance mechanisms in food allergy

Food allergies (FAs) significantly impact quality of life. Allergen-specific immunotherapy (AIT) shows promise but faces limitations such as prolonged treatment duration, systemic side effects, and poor compliance, especially in pediatric and elderly populations. Complementary and alternative medicine (CAM) may enhance AIT efficacy and safety, yet the mechanisms underlying immune tolerance remain poorly understood. This study employed an integrated in silico approach combining network pharmacology, molecular simulation, and metabolomics to investigate anti-allergic Jamu medicinal plants in FA. Active compounds from 13 medicinal plants were analyzed to predict key targets and pathways. Molecular docking and dynamics simulations assessed compound-target binding affinities, while metabolomics evaluated tissue distribution and bioavailability in lymphoid tissues. The results identified transforming growth factor-beta 1 (TGFB1) as a key target associated with the FoxO signaling pathway and Th17 cell differentiation, both of which are critical for promoting allergic tolerance. MAPK1 and MAPK14 emerged as additional targets, providing insights into the mechanisms of allergy development. Molecular simulations demonstrated strong binding affinities, with quercetin (−9.1 kcal/mol) and genistein (−8.1 kcal/mol) binding to TGFB1, and isoprocurcumenol (−7.1 kcal/mol) and dicinnamoylmethane (−10.1 kcal/mol) binding to MAPK1 and MAPK14, respectively. Metabolomic analysis further showed high genistein accumulation in lymph nodes. In summary, these findings suggest that CAM-AIT integration could significantly improve FA therapeutic outcomes by promoting immune tolerance and modulating inflammatory pathways.