期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 -, 期 -, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgad078
关键词
rheumatoid arthritis; macrophage polarization; immunity; inflammatory response; Tripterygium wilfordii Hook. f
This study validated the therapeutic effect of Tripterygium wilfordii Hook. f. in rheumatoid arthritis by restoring the homeostasis of M1/M2 macrophages. It was found that Triptolide, a component of Tripterygium wilfordii, downregulated the expression of factors secreted by M1 macrophages and inhibited inflammatory signaling pathways.
Objectives To validate the enhanced therapeutic effect of Tripterygium wilfordii Hook. f. (TWHF) in the treatment of rheumatoid arthritis (RA) by restoring homeostasis of M1/M2 macrophages.Methods This study, using random walk models and network pharmacology, examined the molecular targets and mechanism of TWHF in RA. Based on clinical observations and experiments in arthritis animal models, the effects of TWHF on macrophage polarization, related signal pathways, and targets were examined. Triptolide, a component of TWHF, was used to intervene arthritis rats.Key findings Network pharmacological analysis revealed the key RA target genes related to TWHF. TWHF showed a strong correlation with the improvement of inflammatory indicators. TWHF inhibited the factors secreted by M1 macrophages such as IL-1 & beta;, IL-6, CXCL8, TNF-& alpha;, and VEGF-A, but promoted IL-10 from M2 macrophages. Quantitative liquid-phase chip assay showed that triptolide reduced the levels of TNF-& alpha;, CXCL2, and VEGF, while IL-4 and IL-10 were increased in arthritis model. Meanwhile, triptolide inhibited the NF-& kappa;B, PI3K/AKT, and p38 MAPK signaling pathways, which in turn improved the RA joint inflammation and fixed immune imbalance.Conclusions Triptolide downregulate the expression of M1 macrophage-secreted factors that inhibit the overactivation of inflammatory signaling pathways.
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