Abstract
Objective Si Miao San (SMS) is a traditional Chinese formula used in China to treat rheumatic diseases. To date, its mechanism in rheumatoid arthritis (RA) treatment is uncertain. Our study aims to assess the antiarthritic effects of SMS in experimental arthritic rats. Materials and Methods SMS (8.63, 4.31, and 2.16 g/kg/day) was orally administered after the first immunization from day 14 to day 53. The effects of SMS on rats with collagen-induced arthritis (CIA) were evaluated by arthritis score and histological assessment. The levels of cytokines and anti-CII antibodies in rat serum were measured by ELISAs. The expression of oxidative stress parameters was detected by biochemical assay kits. The levels of Nrf2, HO-1, NQO1, and PTEN were determined by western blotting. Results Medium- and high-dose SMS treatment significantly decreased arthritis scores and alleviated ankle joint histopathology in the rats with CIA. It inhibited the production of IL-6, TNF-α, COX-2, and PGE2 in rat serum. SMS also suppressed the expression of anti-CII antibodies IgG1 and IgG2a. Moreover, SMS significantly suppressed the levels of MDA and MPO in the synovial tissues while increasing the levels of SOD and CAT in the rats with CIA. The levels of Nrf2, HO-1, NQO1, and PTEN were upregulated by SMS in rat synovial tissues. Conclusions This study demonstrated that SMS effectively alleviated the disease progression of CIA by decreasing the levels of proinflammatory cytokines and reducing oxidative stress damage, as indicated by IL-6, TNF-α, COX-2, and PGE2 levels; inhibiting the overproduction of MDA and MPO; and enhancing antioxidant enzymes by upregulating the Nrf2/ARE/PTEN signalling pathway.
Highlights
Rheumatoid arthritis (RA) is regarded as a serious threat to human health, affecting approximately 0.5–1.0% of people worldwide [1]. e aetiology and pathogenesis of RA have not been completely clarified
Sixty healthy male Wistar rats weighing 150 g to 200 g were procured from the Hubei Provincial Laboratory Animal Center. e study was approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-A20170504). e rats were maintained in the Central Animal House of Tongji Hospital (Animal Certificate of Conformity: SCXK (Hubei) 2015-0018) under controlled temperature (22 ± 4°C). e rats had easy access to standard food and water
Our study found that Si Miao San (SMS) significantly increased the levels of superoxide dismutase (SOD) and CAT and significantly reduced the levels of MPO and MDA in the rats with collagen-induced arthritis (CIA). erefore, the antioxidant effects of SMS via the upregulation of antioxidant enzymes had an antiarthritic effect on the rats with CIA
Summary
Rheumatoid arthritis (RA) is regarded as a serious threat to human health, affecting approximately 0.5–1.0% of people worldwide [1]. e aetiology and pathogenesis of RA have not been completely clarified. It is believed that the main pathogenesis of RA involves multiple inflammatory cascades, leading to persistent synovial hyperplasia and inflammation and cartilage and bone damage [2]. Proinflammatory mediators, including interleukin (IL), TNF-α, and prostaglandin E2 (PGE2), have been reported to play essential roles in synovial inflammation, hyperplasia, and joint destruction [3]. In response to these changes in joints, fibroblast-like synovial cells (FLSs) stimulate the production of the chemokine cyclooxygenase-2 (COX-2), which in turn aggravates joint inflammation and injury. Proinflammatory cytokines promote the Evidence-Based Complementary and Alternative Medicine expression of ROS and nitrogen species and interact to further exacerbate tissue damage. Proinflammatory cytokines promote the Evidence-Based Complementary and Alternative Medicine expression of ROS and nitrogen species and interact to further exacerbate tissue damage. us, inhibiting inflammation and alleviating oxidative stress may be effective treatments against RA
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