Active Ingredients and Potential Mechanism of Additive Sishen Decoction in Treating Rheumatoid Arthritis with Network Pharmacology and Molecular Dynamics Simulation and Experimental Verification

• DOI: 10.2147/dddt.s489323
• Publication Date: 2025-01-21T01:35:11Z
• Authors: Jinhong Ren; Ze Liu; Xiaoming Qi; Xiangda Meng; Linglin Guo; Yating Yu; Tao Dong; Qingshan Li
• Keywords: Decoction

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which macrophages produce cytokines that enhance inflammation and contribute to the destruction of cartilage bone.Additive Sishen decoction (ASSD) widely used traditional Chinese medicine for treatment RA; however, its active ingredients mechanism therapeutic effects remain unclear.Methods: To predict key targets ASSD, we constructed "drug-ingredient-target-disease" protein-protein interaction networks.Gene ontology Kyoto Encyclopedia Genes Genomes enrichment analyses were performed explore potential mechanism.The activity predicted was verified lipopolysaccharide-stimulated macrophages.The binding mode between elucidated using molecular docking dynamics simulation.Results: In all, 75 ASSD 1258 RA analyzed, kaempferol, luteolin, quercetin considered components mainly act through inflammation-related pathways, such as PI3K-AKT, TNF, IL-17 signaling ameliorate RA.Transcriptome sequencing suggested kaempferol-, luteolin-, quercetin-mediated inhibition glycolysis reduced lipopolysaccharide-induced production proinflammatory factors.In vitro experiments indicated decreased Glut1 LDHA expression by diminishing PI3K-AKT inhibit glycolysis.Molecular dynamic simulation revealed stably occupied hydrophobic pocket PI3Kδ.Conclusion: Our results show PI3Kδ-mediated anti-inflammatory responses elicited are crucial efficacy against RA.