Effects of Duhuo Jisheng Decoction on TNF-α-induced proliferation,apoptosis and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis
- VernacularTitle:独活寄生汤对TNF-α诱导的类风湿性关节炎成纤维样滑膜细胞增殖、凋亡和炎症的影响
- Author:
Jing-Ruo WU
1
;
Ya-Nan BU
;
Jin-Ru YUE
;
Jia CHEN
;
Gui-Yu WANG
;
Yu-Min ZHANG
Author Information
- Keywords: Duhuo Jisheng Decoction; rheumatoid ar-thritis; fibroblast-like synoviocytes; proliferation; ap-optosis; inflammatory factors; TLR4/MyD88/NF-κB signaling pathway
- From: Chinese Pharmacological Bulletin 2024;40(9):1665-1673
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the effect of serum contai-ning Duhuo Jisheng Decoction on the proliferation,ap-optosis and inflammation of fibroblast-like synoviocytes(FLS)induced by tumor necrosis factor-α(TNF-α)in rheumatoid arthritis(RA)and to reveal the under-lying mechanism.Methods The MH7A cells were divided into five groups:normal group(10%blank se-rum),model group(10 μg·L-1 TNF-α+10%blank serum),Duhuo Jisheng Decoction low(10 μg·L-1 TNF-α+2.5%drug-containing serum+7.5%blank serum),medium(10 pg·L-1 TNF-α+5%drug-con-taining serum+5%blank serum),high(10 μg·L-1 TNF-α+10%drug-containing serum)dose group.The concentration of serum containing Duhuo Jisheng Decoction was screened by MTT method.Cell prolifer-ation was detected using EdU staining.The expression of proliferation marker Ki67 was detected using immu-nofluorescence staining.The apoptosis rate was meas-ured by flow cytometry.The contents of IFN-γ,IL-4,IL-6 and IL-10 in each group were detected by ELISA.The mRNA and protein expression of Bax,Bcl-2,caspase-3 and TLR4/MyD88/NF-κB signaling pathway were detected by RT-qPCR and Western blot.Results Compared with the normal group,the cell prolifera-tion activity of the model group significantly increased,and the level of apoptosis decreased.The content of IFN-γ and IL-6 increased,and the content of IL-4 and IL-10 decreased.The TLR4/MyD88/NF-κB signaling pathway was activated.After the intervention of low,medium and high dose groups of serum containing Du-huo Jisheng Decoction,it could effectively improve the abnormal proliferation of cells and enhance apoptosis.At the same time,it inhibited the inflammatory re-sponse and the activation of TLR4/MyD88/NF-κB sig-naling pathway.Conclusions The serum containing Duhuo Jisheng Decoction can inhibit the abnormal pro-liferation of RA-FLS induced by TNF-α and the secre-tion of pro-inflammatory factors,and enhance apoptosis and anti-inflammatory levels.The mechanism may be related to the regulation of TLR4/MyD88/NF-κB sig-naling pathway.