Naringenin as a natural immunomodulator against T cell-mediated autoimmune diseases: literature review and network-based pharmacology study

T cells, especially CD4+ T helper (Th) cells, play a vital role in the pathogenesis of specific autoimmune diseases. Naringenin, a citrus flavonoid, exhibits anti-inflammatory, anti-oxidant, and antitumor properties, which have been verified in animal autoimmune disease models. However, naringenin's possible effects and molecular mechanisms in T cell-mediated autoimmune diseases are unclear. This review summarizes the findings of previous studies and predicts the target of naringenin in T cell-mediated autoimmune disorders such as multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis through network pharmacology analysis. We performed DAVID enrichment analysis, protein-protein interaction analysis, and molecular docking to predict the positive effect of naringenin on T cell-mediated autoimmune disorders. Sixteen common genes were screened, among which the core genes were PTGS2, ESR1, CAT, CASP3, MAPK1, and AKT1. The possible molecular mechanism relates to HIF-1, estrogen, TNF, and NF-κB signaling pathways. Our findings have significance for future naringenin treatment of T cell-mediated autoimmune diseases.