Multi-target regulation mechanisms of systemic lupus erythematosus, a network pharmacology and molecular docking...

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by persistent immune activation and multi-organ damage. In this study, we integrated network pharmacology, molecular docking, and in vitro validation to identify and prioritize the active compounds, targets, and regulatory pathways of Artemisia argyi (AA). We identified nine candidate active compounds of AA and 380 predicted protein targets. Intersecting these with 218 SLE-associated genes yielded 19 overlapping targets, among which IL2, CASP3, ACE, PPARG, HSP90AA1, and ANXA5 exhibited the highest network connectivity. Functional enrichment analyses highlighted key pathways, including leukocyte activation, IL-17 signaling, and Th17 cell differentiation. Molecular docking revealed favorable binding affinities of quercetin and naringenin with several core targets. Among these, peroxisome proliferator-activated receptor gamma (PPARG) was selected for exploratory validation based on its high network centrality, favorable docking profile, characterized by strong binging affinities (<-5.5 kcal/mol) for both quercetin and naringenin. Subsequent bioinformatic screening identified LTF, CD72, IL13, CHI3L1, and TLR9 as putative SLE-associated genes regulated by PPARG. Experimentally, AA water extract (AAW) upregulated the expression of PPARG and these downstream genes in THP-1-derived macrophages, whereas pharmacological inhibition of PPARG significantly attenuated these effects. These findings suggest that AA modulate PPARG-dependent transcriptional signaling in immune cells, presenting a candidate mechanism that warrants further validation in disease-relevant models.