Andrographolide (AD) is the main compound distributed in medicinal herb Andrographis paniculata and exhibits anti-inflammatory activity. AD has been used for the treatment of multiple inflammatory diseases. However, the therapeutic value of AD on human rheumatoid arthritis (RA) remains unclear. In this study, we investigated the effects of AD on collagen-induced arthritis (CIA) and human RA synovial fibroblasts (RA-SFs). CIA mice were treated with AD (dissolved in 0.5% CMC-Na, 100 mg/kg per day) or vehicle (0.5% CMC-Na) daily by oral gavage for 2 weeks. The arthritis severity and joint destruction were assessed. Serum anti-collagen II antibody (anti-CII Abs) and cytokines were determined by ELISA. TNFα-stimulated human RA-SFs were treated with varying doses of AD for in vitro investigation. Results showed that AD significantly attenuated the arthritis severity and joint damage. AD treatment significantly reduced the production of serum anti-CII, TNFα, IL-1β, and IL-6. In vitro, AD decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA-SFs in a dose-dependent manner. AD treatment reduced the TNFα-induced phosphorylation of p38 MAPK and ERK1/2 in a dose-dependent manner. Thus, our findings suggest that AD confers protective effects on autoimmune arthritis through inhibiting MAPK pathways.
Rheumatoid arthritis (RA) is a common chronic autoimmune disease in women. This research aims to disclose the probable function of lncRNA H19 in MH7A cells. The influences of tumor necrosis factor-α (TNF-α) on cell viability, apoptosis, and inflammatory factor expression were, respectively, detected through cell counting kit-8 (CCK-8), flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) assay and Western Blot. The levels of H19 and TAK1 were, respectively, tested through qRT-PCR and Western blot. The expression of NF-κB and JNK/p38MAPK pathway-associated proteins was tested through Western blot. We found that TNF-α reduced MH7A cell viability in a concentrationdependent manner and facilitated apoptosis and IL-8, IL-1β, and IL-6 production. Besides, TNF-α treatment raised the level of H19 in MH7A cells. Moreover, H19 silence reduced the levels of inflammatory cytokines, while overexpression of H19 reversed this effect. TNF-α treatment elevated the expression of inflammatory cytokines by up-regulating H19. Furthermore, overexpression of H19 promoted TAK1 phosphorylation. Following studies revealed that H19 activated NF-κB and JNK/p38 MAPK pathways by promoting TAK1 phosphorylation.
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