Tanshinone IIA Suppresses Proliferation and Inflammatory Cytokine Production of Synovial Fibroblasts from Rheumatoid Arthritis Patients Induced by TNF-α and Attenuates the Inflammatory Response in AIA Mice

Abstract

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease in which activated RA fibroblast-1ike synoviocytes (RA-FLSs) are one of the main factors responsible for inducing morbidity. Previous reports have shown that RA-FLSs have proliferative features similar to cancer cells, in addition to causing cartilage erosion that eventually causes joint damage. Thus, new therapeutic strategies and drugs that can effectively contain the abnormal hyperplasia of RA-FLSs and restrain RA development are necessary for the treatment of RA. Tanshinone IIA (Tan IIA), one of the main phytochemicals isolated from Salvia miltiorrhiza Bunge, is capable of promoting RA-FLS apoptosis and inhibiting arthritis in an AIA mouse model. In addition, RA patients treated at our clinic with Tan IIA showed significant improvements in their clinical symptoms. However, the details of the molecular mechanism by which Tan IIA effects RA are unknown. To clarify this mechanism, we evaluated the antiproliferative and inhibitory effects of proinflammatory factor production caused by Tan IIA to RA-FLSs. We demonstrated that Tan IIA can restrict the proliferation, migration, and invasion of RA-FLSs in a time-and dose-dependent manner. Moreover, Tan IIA effectively suppressed the increase in mRNA expression of some matrix metalloproteinases and proinflammatory factors induced by TNF-a in RA-FLSs, resulting in inflammatory reactivity inhibition and blocking the destruction of the knee joint. Through the integration of network pharmacology analyses with the experimental data obtained, it is revealed that the effects of Tan IIA on RA can be attributed to its influence on different signaling

New bitongling (NBTL) ameliorates rheumatoid arthritis in rats through inhibiting JAK2/STAT3 signaling pathway

“… 35 Therefore, repressing of FLS proliferation and inducing of cell apoptosis are considered to be a useful strategy for the treatment of RA. 36 , 37 In present study, our in vitro experiments results showed that NBTL could significantly induced cell apoptosis and hindered proliferation of FLS isolated from RA rat, which is consistent with the results of animal experiments in vivo . It also suggested that NBTL might play its therapeutic effect on rheumatoid arthritis through facilitating apoptosis and restraining proliferation of FLS.…”

Bone innervation and vascularization regulated by osteoclasts contribute to refractive pain-related behavior in the collagen antibody-induced arthritis model

“…However, we are not aware of studies that correlates this to the remaining pain observed in subsets of patients. Moreover, we did not observe an anti-inflammatory effect of T06 as previously reported [38], which could be a model or treatment time-dependent difference. Nonetheless, our data show that two osteoclast inhibitors attenuated refractive hypersensitivity in the CAIA model without affecting joint inflammation.…”

Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal Products in Rheumatoid Arthritis

“…Moreover, RA patients treated at clinic with Tan IIA showed significant improvements in their clinical symptoms. After exploring, a researcher found that Tan IIA could effectively inhibit the increased mRNA expression of multiple matrix metalloproteinases (including MMP2, MMP3, MMP8, and MMP9) and proinflammatory factors in RA-FLSs stimulated by induced by TNF-α, resulting in the inhibition of inflammatory reactivity and end of knee joint destruction, which indicates the promising therapeutic role in the treatment of RA and shows potential to improve the life quality of RA patients ( Du et al, 2020 ). Besides, Celastrol, Ikarisoside, and AKBA (mastic acid active ingredient) suppress the activity of MMP9, one of the transcription factor NF-κB-mediated genes ( Choi et al, 2010 ; Xiao et al, 2018 ).…”