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10.1111/bph.13421 http://scihub22266oqcxt.onion/10.1111/bph.13421 C5341335!5341335!26750154     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26750154&cmd=llinks): Failed to open stream: HTTP request failed! 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Madecassoside ameliorates bleomycin?induced pulmonary fibrosis in mice through promoting the generation of hepatocyte growth factor via PPAR?? in colon |pdf=|usr=}}{{26750154}} gab.com Text Madecassoside ameliorates bleomycin induced pulmonary fibrosis in mice through promoting the generation of hepatocyte growth factor via PPAR in colon JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26750154 #FOAvip Background and Purpose: Madecassoside has potent anti?pulmonary fibrosis (PF) effects when administered p.o., despite having extremely low oral bioavailability. Herein, we explored the mechanism of this anti?PF effect with regard to gut hormones. Experimental Approach: A PF model was established in mice by intratracheal instillation of bleomycin. Haematoxylin and eosin stain and Masson's trichrome stain were used to assess histological changes in the lung. Quantitative?PCR and Western blot detected mRNA and protein levels, respectively, and cytokines were measured by ELISA. Small interfering RNA was used for gene?silencing. EMSA was applied to detect DNA?binding activity. Key Results: Administration of madecassoside, p.o., but not its main metabolite madecassic acid, exhibited a direct anti?PF effect in mice. However, i.p. madecassoside had no anti?PF effect. Madecassoside increased the expression of hepatocyte growth factor (HGF) in colon tissues, and HGF receptor antagonists attenuated its anti?PF effect. Madecassoside facilitated the secretion of HGF from colonic epithelial cells by activating the PPAR?? pathway, as shown by an up?regulation of PPAR?? mRNA expression, nuclear translocation and DNA?binding activity both in vitro and in vivo. Also GW9662, a selective PPAR?? antagonist, almost completely prevented the madecassoside?induced increased expression of HGF and amelioration of PF. Conclusions and Implications: The potent anti?PF effects induced by p.o. madecassoside in mice are not mediated by its metabolites or itself after absorption into blood. Instead, madecassoside increases the activity of PPAR??, which subsequently increases HGF expression in colonic epithelial cells. HGF then enters into the circulation and lung tissue to exert an anti?PF effect. Twit Text FOAVip Madecassoside ameliorates bleomycin induced pulmonary fibrosis in mice through promoting the generation of hepatocyte growth factor via PPAR in colon ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26750154 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26750154 #FOAvip English Wikipedia <ref>{{Cite pmid|26750154}}</ref> Madecassoside ameliorates bleomycin?induced pulmonary fibrosis in mice through promoting the generation of hepatocyte growth factor via PPAR?? in colon #MMPMID26750154 Xia Y; Xia Y; Lv Q; Yue M; Qiao S; Yang Y; Wei Z; Dai Y Br J Pharmacol 2016[Apr]; 173 (7): 1219-35 PMID26750154show ga Background and Purpose: Madecassoside has potent anti?pulmonary fibrosis (PF) effects when administered p.o., despite having extremely low oral bioavailability. Herein, we explored the mechanism of this anti?PF effect with regard to gut hormones. Experimental Approach: A PF model was established in mice by intratracheal instillation of bleomycin. Haematoxylin and eosin stain and Masson's trichrome stain were used to assess histological changes in the lung. Quantitative?PCR and Western blot detected mRNA and protein levels, respectively, and cytokines were measured by ELISA. Small interfering RNA was used for gene?silencing. EMSA was applied to detect DNA?binding activity. Key Results: Administration of madecassoside, p.o., but not its main metabolite madecassic acid, exhibited a direct anti?PF effect in mice. However, i.p. madecassoside had no anti?PF effect. Madecassoside increased the expression of hepatocyte growth factor (HGF) in colon tissues, and HGF receptor antagonists attenuated its anti?PF effect. Madecassoside facilitated the secretion of HGF from colonic epithelial cells by activating the PPAR?? pathway, as shown by an up?regulation of PPAR?? mRNA expression, nuclear translocation and DNA?binding activity both in vitro and in vivo. Also GW9662, a selective PPAR?? antagonist, almost completely prevented the madecassoside?induced increased expression of HGF and amelioration of PF. Conclusions and Implications: The potent anti?PF effects induced by p.o. madecassoside in mice are not mediated by its metabolites or itself after absorption into blood. Instead, madecassoside increases the activity of PPAR??, which subsequently increases HGF expression in colonic epithelial cells. HGF then enters into the circulation and lung tissue to exert an anti?PF effect. äMadecassoside ameliorates bleomycin?induced pulmonary fibrosis in mice(epmc).pdf DeepDyve Pubget Overpricing