Objective. This study aimed to investigate whether berberine exerted anti-inflammatory and antiproliferative effects on the fibroblast-like synoviocytes of rheumatoid arthritis (FLS-RA) through regulating the lysophosphatidic acid (LPA) function.Methods. Firstly, the expression levels of LPA and lysophosphatidic acid receptor 1 (LPA₁) in RA patients, osteoarthritis (OA) patients, and healthy controls were detected. Moreover, molecular docking was employed to characterize the binding sites of berberine in the predicted protein targets. Later, FLS-RA were stimulated using berberine, LPA, and the specific inhibitor (Ki16425) of LPA_1,thereafter, the effects on the proliferation, apoptosis, the release of inflammatory mediators of FLS-RA, and the MAPK pathway were observed.Results. Compared with healthy controls (n = 25), the plasma LPA level (n = 28) and synovial fluid (n = 10) were markedly higher in RA patients. LPA₁was highly expressed in RA patients (n = 4) relative to that in OA patients (n = 4). Berberine remarkably inhibited the proliferation and the excessive production of IL-6 and TNF-αin FLS-RA, whereas suppressing the expression of K-ras, c-Raf, and p-38/ERK-phosphorylation. In addition, berberine inhibited the LPA-induced p-38/ERK-phosphorylation through binding to LPA₁.Conclusions. LPA plays a certain role in promoting the proliferation and inflammation of FLS-RA. Berberine potentially modulates LPA function to suppress the proliferation and inflammation of FLS-RA through blocking the p38/ERK MAPK pathway mediated by LPA₁. These findings suggest that, berberine possesses potential lipid-regulating, antiarthritis, and synovial hyperplasia inhibition activities against RA, which may provide a promising therapeutic target for the clinical drug development for RA patients with dyslipidemia and high CVD risk.

Objective. Simiao pill (SM), a traditional Chinese formula, has been used as an antirheumatic drug in clinical practice for hundreds of years. Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia, cartilage destruction, and joint damage. This study was designed to investigate the protective effects of SM on collagen-induced arthritis (CIA) in rats. It also aimed to explore whether this protective effect of SM was related to the inhibition of the ATX-LPA and MAPK signalling pathways.Materials and Methods. Rats were injected with a collagen II emulsion at the end of the tail and on the back to induce arthritis. Treatment with different doses of SM was conducted by intragastric administration. Then, body weights and arthritis scores were measured. The serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, C-reactive protein (CRP), osteoprotegerin (OPG), autotaxin (ATX), and lysophosphatidic acid (LPA) were determined by ELISA. Pathological changes in the joints were measured by micro-CT and assessed via haematoxylin-eosin (H&E) staining. The expression of ATX, LPA receptor 1 (LPA1) was detected by immunohistochemical staining, and the expression of mitogen-activated protein kinase (MAPK) was detected by Western blotting.Results. SM significantly alleviated arthritis symptoms, inhibited bone erosion, and decreased the levels of TNF-α, IL-1β, CRP, ATX, and LPA in the sera of CIA rats. Importantly, SM clearly reduced the protein expression of LPA1 and ATX. The activation of the MAPK signalling pathway was also inhibited by SM in the synovial tissues of CIA rats.Conclusions. The antirheumatic effects of SM were associated with the regulation of the ATX-LPA and MAPK pathways, the suppression of proinflammatory cytokine production, and the alleviation of cartilage and bone injury. These findings suggest that SM might be a promising alternative candidate for RA therapy.