Anti-inflammatory and osteoprotective effects of Shi-Wei-Ru-Xiang pills on collagen-induced arthritis in rats via inhibiting MAPK and STAT3 pathways. (10th January 2023)

• Record Type: Journal Article
• Authors: Xiong, Hui; Meng, Fengping; Luo, Miao; Chen, Weiwu; Tian, Juan; Chen, Lunju; Ju, Yankun; Mei, Zhinan
• Is Part Of: Journal of ethnopharmacology. Volume 300(2022)
• Publication Date: 2023-01-10
• Subjects: Rheumatoid arthritis -- Cytokines -- MAPK -- STAT3 -- Chondrocytes apoptosis -- Tibetan medicine; RA rheumatoid arthritis -- SW Shi-Wei-Ru-Xiang Pills -- CIA collagen-induced arthritis -- MAPK Mitogen-activated protein kinases -- Erk extracellular signal-regulated kinase -- STAT3 Signal Transducer and Activator of Transcription 3; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115693
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Shi-Wei-Ru-Xiang pills (SW) as a tradition Tibetan medicine has been clinically proved effective in rheumatoid arthritis (RA) treatment. However, the underlying mechanism of SW remains unclear. Aim of the study: This study aimed to investigate the anti-arthritic effect of SW and its possible mechanisms of action. Materials and methods: A CIA rat model in vivo, and IL-1β-stimulated synoviocytes or chondrocytes and a co-culture system (IL-1β-stimulated synoviocytes/chondrocytes) in vitro were used to evaluate the effects of SW on the treatment of RA. Arthritic score, paw swelling rate, hematoxylin-eosin (HE) staining, and Safranin-O-Fast green (S–O) staining were used to evaluate the anti-arthritic activity of SW in CIA rats. TUNEL assay or flow cytometry were performed to measure chondrocytes apoptosis in vivo and in vitro . The effects of SW on the expression and production of pro-inflammatory cytokines were assessed by qRT-PCR and Elisa. The inhibitory effects of SW on the phosphorylation of p38, Erk1/2, and STAT3 were analyzed by Western blot. Results: SW treatment significantly alleviated paw swelling, severity of arthritic and cartilage destruction in CIA rats. Moreover, SW decreased the expression of mRNAs of proinflammatory cytokines including TNF-α, IL-1β and IL-6 in the synovium, suppressed the production of these pro-inflammatory cytokines in serum and hind paws, downregulated the protein expression of p-p38, p-Erk1/2 and p-STAT3, and protected the chondrocytes apoptosis in CIA rats. Consistent with the results in vivo, SW also inhibited the activation of MAPK and STAT3 pathways, suppressed the expression of pro-inflammatory cytokines in IL-1β-stimulated synoviocytes, and attenuated chondrocytes apoptosis in IL-1β-stimulated chondrocytes. In the co-culture system, SW pre-treatment in IL-1β-stimulated synoviocytes exhibited inhibition of chondrocytes apoptosis, which was associated with attenuation of inflammation in synoviocytes. Conclusion: These results suggested that the underlying mechanisms by which SW exerts its anti-arthritis effect may be related to the reduction of proinflammatory cytokine levels, inhibition of p38, Erk1/2 and STAT3 phosphorylation, and attenuating of chondrocyte apoptosis. Graphical abstract: Image 1 Highlights: Shi-Wei-Ru-Xiang pills alleviated severity of arthritic, cartilage destruction and relieved inflammatory symptoms in CIA rats. Shi-Wei-Ru-Xiang pills reduced proinflammatory cytokine levels through inhibiting MAPK and STAT3 pathways both in vivo and in vitro . Shi-Wei-Ru-Xiang pills regulated synoviocytes-chondrocytes crosstalk and inhibited the chondrocytes apoptosis.