Wedelolactone ameliorates synovial inflammation and cardiac complications in a murine model of collagen-induced arthritis by inhibiting NF-κB/NLRP3 inflammasome activation

作者：Jingjing Cao, Yanhui Ni, Xiaoran Ning, Huaxing Zhang · 发表于：Folia Histochemica et Cytobiologica · 年份：2022 · DOI：10.5603/fhc.a2022.0025 · 被引用次数：11 · 研究领域：Medicinal Plants and Neuroprotection、Phytochemicals and Medicinal Plants、Rheumatoid Arthritis Research and Therapies

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disorder associated with joint damage and attendant cardiovascular complications. Wedelolactone (Wed), derived from Eclipta alba, possesses anti-inflammatory activity. Whether Wed regulates RA inflammation and related heart damage remains unknown. MATERIAL AND METHODS: A murine model of collagen-induced arthritis (CIA) was well-established by two subcutaneous injections of type II collagen (days 0 and 21). Wed was then administered via intraperitoneal injection every other day from day 28 to day 48. Joint swelling was monitored and paw thickness was calculated. Histopathological changes in synovial tissues or ankle cartilage were evaluated by hematoxylin and eosin (H&E) and Safranin O-Fast Green staining. The concentrations of inflammatory factors in serum and synovial tissues were detected by ELISA. The qRT-PCR, Western blotting, immunohistochemistry (IHC), and immunofluorescence (IF) were performed to assess receptor activator of nuclear factor kappa ligand (RANKL), matrix metalloprotease (MMP)-3, NLRP3, caspase-1 (pro- and cleaved forms), p-p65, IκBα, p-IκBα, p65, αsmooth-actin 2 (ACTA2), collagen type I and E-cadherin expression. H&E and Masson staining were used to assess the pathological alterations in the heart. RESULTS: Treatment with Wed ameliorated ankle joint swelling and cartilage degradation. Wed decreased the infiltration of inflammatory cells, the release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α,...