期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 83, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2020.106384
关键词
Daphne genkwa; Flavonoids; Genkwanin; Rheumatoid arthritis
资金
- Key R&D projects in modernization of Chinese Medicine [2018YFC1707105]
- Double Firstrate Discipline Innovation Team [CPU2018GF05, CPU2018GY11]
- National Natural Science Foundation of China [81873185, 81860773, 81573565]
- Natural Science Foundation of Jiangsu Province, Jiangsu, China [BK20181327]
Objective: This study aims to select the most effective anti-Rheumatoid Arthritis (RA) component of flavonoids from Daphne genkwa Sieb. et Zucc. by anti-inflammatory and immunomodulatory effects in vitro, and to elucidate the mechanism. Methods: The anti-inflammatory and immunomodulatory effects of total flavonoids (TF) and four flavonoid components (genkwanin, hydroxygenkwanin, luteolin and apigenin) were determined by pharmacological approach in LPS-induced RAW 264.7 macrophages and ConA-induced T lymphocytes. Principal component analysis (PCA) was used to obtain the optimal anti-RA component in vitro. Western blot and real-time quantitative PCR (q-PCR) were used to explore the mechanisms. Finally, the in vitro anti-RA effect was verified by human rheumatoid arthritis fibroblast-like synoviocytes (FLSs). Results: TF and four flavonoids significantly reduced the expressions of NO, iNOS, TNF-alpha, IL-6, IFN-gamma and IL-2. PCA showed that genkwanin was the most effective anti-RA component in vitro. Genkwanin inhibited nuclear factor-kappa B (NF-kappa B) pathway by decreasing the phosphorylation levels of IKK, I kappa B and NF-kappa B, and down-regulated the expressions of iNOS, COX-2 and IL-6 mRNA. Genkwanin also inhibited the abnormal proliferation of FLSs and down-regulated the secretions of NO and IL-6. Conclusion: The most effective anti-RA component was genkwanin. Genkwanin exerts anti-RA effect through down-regulating the activation of NF-kappa B pathway and mRNA expressions of inflammatory mediators, and also by inhibiting the abnormal proliferation of FLSs and its NO and IL-6 secretion levels.
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