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Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro.


ABSTRACT: 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-?1 (TGF-?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 (?1) collagen and fibronectin in UUO kidneys. Phosphorylation of Smad-2/3 induced by TGF-?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.

SUBMITTER: Chiang CK 

PROVIDER: S-EPMC3101620 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro.

Chiang Chih-Kang CK   Sheu Meei-Ling ML   Lin Yi-Wei YW   Wu Cheng-Tien CT   Yang Chin-Ching CC   Chen Min-Wei MW   Hung Kuan-Yu KY   Wu Kuan-Dun KD   Liu Shing-Hwa SH  

British journal of pharmacology 20110601 3


<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Anti-fibrotic effects in vivo were assayed in a rat  ...[more]

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