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標題: Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro
作者: Chiang, C.K.
Sheu, M.L.
Lin, Y.W.
Wu, C.T.
Yang, C.C.
Chen, M.W.
Hung, K.Y.
Wu, K.D.
Liu, S.H.
Project: British Journal of Pharmacology
期刊/報告no:: British Journal of Pharmacology, Volume 163, Issue 3, Page(s) 586-597.
BACKGROUND AND PURPOSE Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. The present study investigated, in vivo and in vitro, the anti-fibrotic and anti-inflammatory effects, particularly on the epithelial to mesenchymal transition of renal tubular cells, exerted by honokiol, a phytochemical used in traditional medicine, and mechanisms underlying these effects. EXPERIMENTAL APPROACH Anti-fibrotic effects in vivo were assayed in a rat model of renal fibrosis [the unilateral ureteral obstruction (UUO) model]. A rat tubular epithelial cell line (NRK-52E) was stimulated by transforming growth factor-beta 1 (TGF-beta 1) and treated with honokiol to explore possible mechanisms of these anti-fibrotic effects. Gene or protein expression was analysed by Northern or Western blotting. Transcriptional regulation was investigated using luciferase activity driven by a connective tissue growth factor (CTGF) promoter. KEY RESULTS Honokiol slowed development of renal fibrosis both in vivo and in vitro. Honokiol treatment attenuated tubulointerstitial fibrosis and expression of pro-fibrotic factors in the UUO model. Honokiol also decreased expression of the mRNA for the chemokine CCL2 and for the intracellular adhesion molecule-1, as well as accumulation of type I (alpha 1) collagen and fibronectin in UUO kidneys. Phosphorylation of Smad-2/3 induced by TGF-beta 1 and CTGF luciferase activity in renal tubular cells were also inhibited by honokiol. CONCLUSIONS AND IMPLICATIONS Honokiol suppressed expression of pro-fibrotic and pro-inflammatory factors and of extracellular matrix proteins. Honokiol may become a therapeutic agent to prevent renal fibrosis.
ISSN: 0007-1188
DOI: 10.1111/j.1476-5381.2011.01242.x
Appears in Collections:生物醫學研究所

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