Kaempferitrin inhibits proliferation, induces apoptosis, and ameliorates inflammation in human rheumatoid arthritis fibroblast‐like synoviocytes

Abstract

Rheumatoid arthritis (RA) is a complex chronic inflammatory disease that is associated with the aberrant activation of fibroblast‐like synoviocytes (FLS). Kaempferitrin is a natural flavonoid glycoside that possesses anti‐inflammatory bioactivity. However, the effect of kaempferitrin on RA has not yet been revealed. The aim of the present study was to investigate the effect of kaempferitrin on human RA‐FLS MH7A cell line. We found that kaempferitrin inhibited proliferation and induced apoptosis of MH7A cells. Kaempferitrin decreased the levels of interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α, matrix metalloproteinase (MMP)‐1, and MMP‐3 in MH7A cells. Moreover, kaempferitrin blocked the activation of nuclear factor‐κB (NF‐κB) and protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways. Furthermore, treatment with kaempferitrin decreased paw thickness and arthritis scores, and reduced the serum levels of IL‐1β, IL‐6, and TNF‐α in a collagen‐induced arthritis mouse model. In conclusion, kaempferitrin inhibited cell proliferation, induced cell apoptosis, and ameliorated inflammation of RA‐FLS by suppressing the NF‐κB and Akt/mTOR pathways.

Cinnamomi ramulus exhibits anti-proliferative and anti-migration effects on MH7A rheumatoid arthritis-derived fibroblast-like synoviocytes through induction of apoptosis & cell arrest and suppression of matrix metalloproteinase

“…Mitochondrial mediated apoptosis is largely regulated by the Bcl-2 protein family. It is well known that the Bcl-2 family proteins, anti-apoptotic proteins such as Bcl-2, inhibit apoptosis, while pro-apoptotic proteins, such as Bax, activate apoptosis in RA [29]. In this study, our results showed that Cinnamomi ramulus increased the expression of Bax in MH7A, as well as decreased the expression of Bcl-2 protein.…”

Identification of Drug Targets and Potential Molecular Mechanisms of Wantong Jingu Tablet in Treatment of Rats with Collagen-Induced Arthritis based on 16S rDNA High-Throughput Sequencing and Metabolomic Analysis

“…The results of clinical manifestations and pathological changes demonstrated that WJT played an important role in suppressing the pathological progression of arthritis in CIA rats, which laid a foundation for the further study. In addition, The aberrant release and recruitment of pro-in ammatory cytokines (TNF-α, IL-1β, and IL-6) are essential to the pathogenesis of RA [17,29,20]. It's well known that both TNFα and IL-1β play roles in the activation and in ltration of immune cells, and contribute to production of in ammatory cytokines and chemokines, thereby resulting in a complex network that promotes in ammatory reactions, cartilage damage and autoimmune pathology [17,21].…”

Identification of drug targets and potential molecular mechanisms of Wantong Jingu Tablet in treatment of rats with collagen-induced arthritis based on 16S rDNA high-throughput sequencing and metabolomic analysis

“…The results of clinical manifestations and pathological changes demonstrated that WJT played an important role in suppressing the pathological progression of arthritis in CIA rats, which laid a foundation for the further study. In addition, The aberrant release and recruitment of pro-in ammatory cytokines (TNF-α, IL-1β, and IL-6) are essential to the pathogenesis of RA [18,20,21]. It's well known that both TNFα and IL-1β play roles in the activation and in ltration of immune cells, and contribute to production of in ammatory cytokines and chemokines, thereby resulting in a complex network that promotes in ammatory reactions, cartilage damage and autoimmune pathology [18,22].…”