RESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial membrane, thus causing stiffness, deformity and dysfunction of joints. To date, no effective antiinflammatory treatments are available for RA. Piceatannol (PIC) is a natural derivative of resveratrol, which has been reported to attenuate the inflammatory response. To evaluate the effect of PIC on RA and to determine the underlying molecular target of PIC, both in vitro and in vivo experiments were performed in the present study. A CIA rat model was established to evaluate the therapeutic effects of PIC. TNFα, IL1ß and IL6 levels in blood were measured by ELISA. Western blotting, immunofluorescence analysis and reverse transcriptionquantitative PCR (RTqPCR) were used to analyze the expression levels of protein and mRNA. In vitro, RAfibroblastlike synoviocytes (FLSs) were pretreated with PIC and subsequently stimulated with TNFα. The results revealed that PIC significantly upregulated the expression levels of proapoptotic proteins such as Bax and cleaved caspase3. PIC also significantly reduced the production of proinflammatory cytokines, including PGE2, IL6 and IL1ß, and significantly downregulated the expression of cyclooxygenase2 at both the mRNA and protein expression levels. Furthermore, PIC downregulated the expression of MMP3 and MMP13, which have been found to be highly expressed in the synovium of patients with RA. Mechanistically, PIC was capable of significantly downregulating the expression levels of proteins involved in the NFκB and MAPK signaling pathways. The results of the in vivo experiments using a rat collageninduced arthritis model demonstrated that PIC decreased the arthritis score and exerted beneficial effects in cartilage and significantly reduced the expression of MMP13. In conclusion, the findings of the present study revealed that PIC could suppress the inflammatory response, promote apoptosis, and exert a significant regulatory effect on the NFκB and MAPK signaling pathways in RAFLSs. Therefore, PIC may represent a potential drug for the future treatment of RA.
Assuntos
Artrite Reumatoide , Sinoviócitos , Animais , Apoptose , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Proliferação de Células , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Ratos , Estilbenos , Sinoviócitos/metabolismoRESUMO
Gastrin is a peptide hormone, which acts not only to regulate gastric acid secretion, but also to exert physiological actions such as the regulation of sodium balance. From a case (n = 95)-control (n = 82) study in Fuyang People's Hospital, Anhui Province, China, we found that the fasting serum gastrin levels are similar in normotensive and hypertensive adults but increased to higher levels in the latter group than in the former group after a mixed meal. We suggest that gastrin is involved in the regulation of blood pressure, possibly via the regulation of sodium and water metabolism and/or renin-angiotensin-aldosterone system. However, the mechanism remains to be determined.