Cepharanthin Alleviate Gouty Arthritis by Inhibiting NLRP3 Inflammasome and Inflammation Factors
10.16466/j.issn1005-5509.2023.12.002
- VernacularTitle:千金藤素通过抑制TLR4-NLRP3炎症小体及炎症因子治疗痛风性关节炎
- Author:
Bin HU
1
;
Jiaoyu RAO
;
Lin JIANG
Author Information
1. 龙华区中心医院 广东,深圳 518110
- Keywords:
gout;
arthritis;
NLRP3 inflammasome;
cytokines;
cepharanthin;
colchicine
- From:
Journal of Zhejiang Chinese Medical University
2023;47(12):1374-1382
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To evaluate the anti-inflammatory effect of cepharanthin in vitro and in vivo,and to explore its mechanism of action in the treatment of gouty arthritis.[Methods]3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay was used to evaluate the effect of cepharanthin on cell viability in RAW264.7 cells.Enzyme linked immunosorbent assay(ELISA)and Western blot methods were used to detect the effects of cepharanthin on secretion and protein expression of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88)and NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/caspase-1 inflammasome in vitro and in vivo.Gouty arthritis model was established by monosodium urate(MSU)stimulation in SD rats.The anti-inflammatory related indexes of cepharanthin were detected.The anti-inflammatory effect of cepharanthin was evaluated by detecting the expression of TNF-α,IL-1β,IL-6 and TLR4-NLRP3 related protein.[Results]The half maximal inhibitory concentration(IC50)of cepharanthin to cell viability in RAW264.7 cells was(62.51±5.36)μmol·L-1,weaker than that of colchicine(26.89±5.14)μmol·L-1.In RAW264.7 cells,1～10 μmol·L-1 cepharanthin significantly inhibited the secretion and mRNA expression of MSU-induced inflammatory factors TNF-α,IL-1β and IL-6,as also protein expression of TLR4-NLRP3 inflammasome.In rats arthritis model,1～10 mg·kg-1 cepharanthin dose-dependently improved toe swelling,and reduced the secretion of inflammatory factors TNF-α,IL-1β and IL-6,and protein expression of TLR4-NLRP3 inflammasome.[Conclusion]Cepharanthin exerts anti-arthritis effects by inhibiting the expression of inflammatory factors TNF-α,IL-1βand IL-6,and the expression of TLR4-NLRP3 inflammasome induced by MSU.
