glaucocalyxin-a and Arthritis--Rheumatoid

The pathogenesis of rheumatoid arthritis (RA) is characterized by synoviocyte hyperplasia and proinflammatory cytokine secretion, as well as the destruction of cartilage and bone. Glaucocalyxin A (GLA) is an alkaloid derived from a Chinese medicinal plant that exhibits anti-inflammatory, anti-tumor and neuroprotective properties. We investigated the effects of GLA on RA-fibroblast-like synoviocytes (FLS cells), and collagen-induced arthritis (CIA), and further explored the underlying mechanisms. GLA inhibited TNF-a-induced RA-FLS proliferation, increased apoptotic ratios and upregulated levels of caspase-3, cleaved PARP, and Bax. GLA also inhibited the expression of IL-10, IL-1β, and IL-6 in vitro. Levels of p-STAT3 were downregulated in a dose-dependent manner. Over-expression of STAT3 partly neutralized the GLA-mediated elevation of caspase-3 and cleaved PARP levels as well as the downregulation of IL-10, IL-1B and IL-6 expression levels. This suggests that GLA inactivated the STAT3 pathway. Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model were inhibited effectively by GLA. Taken together, our data suggest that GLA is a potential long-term therapeutic agent for patients with RA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Arthritis, Experimental; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytokines; Diterpenes, Kaurane; Humans; Inflammation; Male; Mice, Inbred DBA; Rats, Wistar; STAT3 Transcription Factor; Synoviocytes; Th17 Cells; Tumor Necrosis Factor-alpha