[Jintiange Capsules-containing serum inhibits function of fibroblast-like synoviocytes stimulated by TNF-α via...

This study aims to explore the effects and mechanism of Jintiange Capsules-containing serum(JTG-CS) on fibroblast-like synoviocytes(FLS) in human rheumatoid arthritis. The blank serum from SD rats and low, medium, and high-dose JTG-CS samples were prepared. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was employed to determine the amino acid composition and content in the blank serum and JTG-CS. Tumor necrosis factor-α(TNF-α) was used to stimulate FLS for the modeling of inflammation. The proliferation of FLS was determined by the CCK-8 assay. The migration and invasion of FLS were examined by wound healing and Transwell assays. The protein expression of FLS was analyzed by Western blot. JTG-CS significantly inhibited the proliferation, migration, wound healing, and invasion of FLS stimulated by TNF-α, down-regulated the expression of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase(MMP)2, and MMP3, lowered the levels of TNF-α, interleukin(IL)-6, and IL-1β, and inhibited the activation of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor(NF)-κB, and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathways. The treatment with the PI3K agonist reversed the inhibitory effects of JTG-CS on inflammatory cytokines and invasion of FLS stimulated by TNF-α. Compared with the blank serum, JTG-CS showed increased content of 46 amino acids and decreased content of 20 amino acids. JTG-CS inhibited the proliferation, migration, invasion, and inflammation of FLS stimulated by TNF-α by inhibiting the activation of the PI3K/Akt pathway.