XuanBi
Mitigates Rheumatoid Arthritis via Regulation of
ECM
‐Receptor Interactions and
IL
‐17 Signaling: Insights Fro
Hao Zhu, Zhenfeng Pan, Ying Lu, Ping Xia, Weiming He, Jingqi Zeng, Fan Wang, Xiao Liu, Minggang Wei ABSTRACT
Plant‐derived polyphenols possess broad anti‐inflammatory activities and may benefit chronic inflammatory diseases. XuanBi is a traditional Chinese medicine formula containing orally absorbable polyphenolic constituents and is used to treat rheumatoid arthritis (RA). This study investigated its absorbable components and potential mechanisms associated with synovial inflammatory hyperplasia. XuanBi was evaluated in collagen‐induced arthritis (CIA) rats and rheumatoid arthritis synovial fibroblasts (RASFs). Constituents in the decoction and rat serum were characterized by high‐performance liquid chromatography coupled with quadrupole‐Orbitrap mass spectrometry (HPLC‐Q‐Orbitrap‐MS). Predicted targets were intersected with synovial differentially expressed proteins (DEPs), followed by network pharmacology, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and experimental validation. Twenty‐six absorbable constituents were identified, including catechin, quercetin, baicalein, and wogonin, together with 14 candidate proteins associated with RA synovial pathology. Enrichment analysis implicated extracellular matrix (ECM)–receptor interaction, focal adhesion, and interleukin‐17 (IL‐17) signaling. Medium‐ and high‐dose XuanBi reduced joint swelling, synovial hyperplasia, and inflammatory infiltration in CIA rats. In RASFs, XuanBi inhibited proliferation, migration, and invasion. It also downregulated fibronectin 1 (FN1) and caveolin 1 (CAV1), reduced phosphorylation of SRC, focal adhesion kinase (FAK), and FYN, decreased integrin alpha 2b (ITGA2B) + /integrin beta 1 (ITGB1) + cells, and reduced interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α), matrix metallopeptidase 3 (MMP3), and matrix metallopeptidase 9 (MMP9). Overall, XuanBi exerted anti‐inflammatory and anti‐synovial‐hyperplasia effects in experimental RA, accompanied by changes in proteins associated with these pathways, supporting the potential involvement of these pathways and warranting further mechanistic and clinical investigation.