Abstract
Excessive proliferation and inflammation of synovial fibroblasts accelerate and decorate the pathological process of rheumatoid arthritis (RA). Sigesbeckia orientalis L. (SO) is one of the main plant sources for Sigesbeckiae Herba (SH) which has been used traditionally in treating various forms of arthritis and rheumatic pain. However, the anti-arthritic mechanisms of SO are still not clearly understood. In this study, we investigated the therapeutic effects and the underlying mechanisms of SO against collagen type II (C II)-induced RA in rats as well as the interleukin (IL)-1β–induced human synovial SW982 and MH7A cells. For the in vivo studies, thirty-six Wistar male rats were randomly arranged to six groups based on the body weight, and then C II-induced to RA model for 15 days, followed by treatment with the 50% ethanolic extract of SO (SOE, 0.16, 0.78, and 1.56 g/kg) for 35 days. The results suggested that SOE significantly inhibited the formation of pannus (synovial hyperplasia to the articular cavity) and attenuated the cartilage damaging and bone erosion in the CIA-induced rats’ hind paw joints. Moreover, SOE decreased the production of C-reactive protein (CRP) in the serum and the expression of IL-6 and IL-1β in the joint muscles, as well as recovered the decreased regulatory T lymphocytes. The results obtained from the in vitro studies showed that SOE (50, 100, and 200 µg/ml) not only inhibited the proliferation, migration, and invasion of human synovial SW982 cells but also decreased the IL-1β–induced expression of IL-6 and IL-8 both in SW982 and MH7A cells. Besides, SOE reduced the expression of COX-2, NLRP3, and MMP9, and increased the expression of MMP2 in the IL-1β–induced SW982 cells. Furthermore, SOE blocked the activation of NF-κB and reduced the phosphorylation of MAPKs and the expression of AP-1. In conclusion, SOE attenuated the C II-induced RA through inhibiting of MAPKs/NF-κB/AP-1–mediated synovial hyperplasia and inflammation.
Highlights
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune dysfunction, chronic inflammation, synovial tissue hyperplasia, cartilage/bone damaging, and accompanied with progressive loss of joint function (Scott et al, 2010), which significantly affects the life quality of the patients and brings huge economic burden as well as the serious social problems (Scott et al, 2010)
Hong et al reported that Sigesbeckia orientalis L. (SO) attenuated l-carrageenan–induced paw edema and LPS-induced systemic inflammation in mice (Hong et al, 2014), which indicated the potential of SO on RA and valuable to be further investigated
With the innovation of drug development technology, RA treatments from the non-steroidal anti-inflammatory agents (NSAIDs) to biologics have obtained some achievements on improving the life quality of patients
Summary
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune dysfunction, chronic inflammation, synovial tissue hyperplasia, cartilage/bone damaging, and accompanied with progressive loss of joint function (Scott et al, 2010), which significantly affects the life quality of the patients and brings huge economic burden as well as the serious social problems (Scott et al, 2010). Compared with the current modern drugs (e.g. the non-steroidal anti-inflammatory agents, NSAIDs; corticosteroids; disease modifying anti-rheumatic drugs, DMARDs; and biologics, etc.) in clinical application for RA, traditional herbal medicines with the advantages of low-price, good safety, and wide cultural recognition still occupy a huge market. Investigations into the multi-biological mechanisms and quality control of herb medicines could promote the precise applications in clinic and be beneficial to such a group of people. Sigesbeckia herba (SH) widely distributed throughout the world (Pradhan et al, 2018) is a traditional herb medicine with a long history for management of various inflammation-related diseases (especially for rheumatism) in China (Zhong et al, 2019) and some other Asian countries (Jang et al, 2018). With the increasing concerns on this herb medicine for its anti-inflammation and joint protection, it is critical to demonstrate the anti-arthritic effects and mechanisms of SH with modern research approaches
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