Abstract
Background/Aims Jiawei Fengshining (JWFSN) is a new formula originated from Fengshining, a classic formula for the treatment of rheumatoid arthritis (RA). The mechanism of JWFSN in the treatment of RA is still unclear. The aim of this study was to evaluate the effect of JWFSN formula on the inflammatory mediator levels in the serum and the TGF-β1/Smad pathway in the synovium and to explore the underlying mechanisms of JWFSN formula to ameliorate synovial hyperplasia and apoptosis inhibition of synovium in rats with RA. Method SPF female Wistar rats were randomly divided into 6 groups: the blank control group, the model control group, the positive drug group, and the low-, medium-, and high- dose JWFSN groups, with 8 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory mediators, anti-inflammatory mediators, and rheumatoid factor (RF). The pathological condition and apoptosis of the synovial tissue were detected by hematoxylin and eosin (HE) and TUNEL staining, respectively. TGF-β1, p-Smad2, p-Smad3, and Smad7 protein expressions in synovial tissue were measured by western blot assay. In addition, human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A was treated with 20% JWFSN-containing serum to obtain in vitro data. Result The administration of JWFSN was found to ameliorate synovial hyperplasia and promote apoptosis; increase the serum contents of anti-inflammatory mediators; reduce inflammatory mediators and RF contents; and inhibit the TGF-β1/Smad signaling pathway in CIA rats. In vitro JWFSN treatment increased the apoptosis of MH7A cells and decreased cell viability. Additionally, JWFSN treatment inhibited the TGF-β1/Smad signaling pathway in MH7A cells. Interestingly, kartogenin (TGF-β1/Smad pathway activator) treament reversed the effects of JWFSN treatment. Conclusion JWFSN may ameliorate inflammatory factors' abnormality, synovial hyperplasia, and apoptosis inhibition of synovium via the TGF-β1/Smad signaling pathway.
Highlights
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease
Joint swelling was observed clearly in the model group. e level of joint swelling was alleviated in Jiawei Fengshining (JWFSN) and leflunomide treatment rats compared with the model group
To observe the effect of JWFSN on production of inflammatory mediators, anti-inflammatory mediators, and rheumatoid factor, we examined the expression levels of INF-c, IL-1β, tumor necrosis factor-α (TNF-α), IL-4, IL-10, and RF in serum of CIA rats
Summary
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Is disease lasts for a long time and can affect other organs, such as the heart, lungs, and kidney [2]. Rheumatoid arthritis affects 0.5–1.0% of adults [3]. E treatment of RA involves a combination of patient education, rest and exercise, joint protection, medications, and surgery [7]. Nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and steroid and biological response modifiers are commonly used to reduce joint pain or slow disease progression [8]. The application of these treatments has been limited due to the high incidence of side effects [9]
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