| Summary: | 碩士 === 國立中山大學 === 海洋生物科技暨資源學系研究所 === 107 === Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease, characterized by synovium unusual proliferation, pannus formation and joint destruction. In the pannus, the microvascular becomes dysfunctional and disorganized, and bring about restriction of oxygen delivery causes hypoxia. The hypoxic environment induces angiogenesis and metabolic switch, both of them are considered as the important role in the pathogenesis of RA that could be regulated by histone deacetylase (HDAC). In recent years, marine compounds have been consider as an important novel resource for anti-inflammatory drugs discovery on treating human disease. In present studies, we try to demonstrate the effect of PON-1629 which is a coral compound on rheumatoid arthritis. Our results show that PON-1629 could significant decrease inducible nitric oxide synthase (iNOS) protein expression in LPS stimulated RAW 264.7 cell model. In vivo studies, PON-1629 also significantly attenuate arthritis score and paw edema in Type II collagen-induced arthritis (CIA) rat. Therefore, we also observed that PON-1629 decrease bone erosion in micro CT image and could reduce the serum level of IL-1β in CIA rats.Histopathological analysis showed that PON-1629 also could attenuated the histopathological features in CIA model, for instance synovial hyperplasia and bone erosion. Also PON-1629 could decreased angiogenesis-associated and glycolysis-associated protein expression. Based on above data, PON-1629 will be serve as a useful therapeutic agent for the treatment of RA.
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