Ameliorative effect of Alangium chinense (Lour.) Harms on rheumatoid arthritis by reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways

Alangium chinense has been used as traditional folk medicine for centuries to treat rheumatoid arthritis (RA) by Guizhou Miao nationality with remarkable clinical effect. But the mechanism of its anti-RA is not fully clarified.To explore the effect and underlying mechanism of A. chinense against RA.RA rats were induced by CII/IFA, and oral administrated with or without ethyl acetate extracts of Alangium chinense (ACEE) and tripterygium glycosides (GTW). Then arthritis scores, inflammatory factors in serum and histological evaluation were evaluated to assess the degree of joints disease. Proteomics were conducted via LC-MS/MS to clarify the mechanism of ACEE preliminarily, and further examined by immunohistochemistry, immunofluorescence, western botting, and molecular docking.ACEE decreased joints swelling, cell abscission and necrosis of joint tissues arthropathy of RA rats, and attenuated expression of TNF-α, IL-1β, IL-6, PGE2, TGF-β. Meanwhile, differentially expressed proteins in the ACEE treated groups were observed, which were involved in RA, spliceosome, cell adhesion molecules, phagosome and lysosome signaling pathways. Moreover, ACEE significantly ameliorated arthropathy, suppressed JAK-STAT pathway (JAK3, p-JAK3, STAT3, iNOS, RANKL), COX-2 pathway (COX-2, TNF-α, IL-6I, L-1β, 5-LOX), and autophagic signaling pathway (LC3-Ⅰ, LC3-Ⅱ, p62, mTOR). But it showed little effect on the expression of COX-1, JAK1, JAK2, TyK2.It is the first evidence that A. chinense significantly ameliorates RA, and the underlying immune mechanism involves reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways.