Emodin Inhibits Proinflammatory Responses and Inactivates Histone Deacetylase 1 in Hypoxic Rheumatoid Synoviocytes

Chronic inflammation of rheumatoid arthritis (RA) is promoted by proinflammatory cytokines and closely linked to angiogenesis. In the present study, we investigated the anti-inflammatory effects of emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) isolated from the root of Rheum palmatum L. in interleukin 1 beta (IL-1 beta) and lipopolysaccharide (LPS)-stimulated RA synoviocytes under hypoxia. Emodin significantly inhibited IL-1 beta and LPS-stimulated proliferation of RA synoviocytes in a dose-dependent manner under hypoxic condition. Also, enzyme linked immunosorbent assay (ELISA) revealed that emodin significantly reduced the production of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8], mediators [prostagladin E-2 (PGE(2)), matrix metalloproteinase (MMP-13] and MMP-13] and vascular endothelial growth factor (VEGF) as an angiogenesis biomarker in IL-1 beta and LPS-treated synoviocytes under hypoxia. Consistently, emodin attenuated the expression of cyclooxygenase 2 (COX-2), VEGF, hypoxia inducible factor 1 alpha (HIF-1 alpha), MMP-1 and MMP-13 at mRNA level in IL-1 beta and LPS-treated synoviocytes under hypoxia. Furthermore, emodin reduced histone deacetylase (HDAC) activity as well as suppressed the expression of HDAC1, but not HDAC2 in IL-1 beta and LPS-treated synoviocytes under hypoxia. Overall, these findings suggest that emodin inhibits proinflammatory cytokines and VEGF productions, and HDAC1 activity in hypoxic RA synoviocytes.