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Isofraxidin, a coumarin component improves high-fat diet induced hepatic lipid homeostasis disorder and macrophage inflammation in mice

Abstract

Isofraxidin (IF) is a coumarin compound produced in the functional foods Siberian ginseng and Apium graveolens. The first objective of this study was to investigate the protective effects and putative methods of IF in combating lipotoxicity in vitro and in vivo. Oleic acid was used to induce lipid turbulence in human hepatoma cell (HepG2). Alterations in triglyceride metabolism, inflammation and oxidative status were monitored. Results show that IF mainly reduced triglyceride accumulation, TNF-α release and ROS activation in metabolic disordered cells. Next, a high-fat diet which induced a non-alcoholic fatty liver disease was used to evaluate the therapeutic action of IF Our results show that treatment with IF significantly inhibited the high-fat diet-induced elevation in body weight, liver weight, lipid metabolism (TG, TC and HDL-C) and hepatic injury in mice. In biochemical terms, treatment with IF resulted in enhanced phosphorylation of AMPKα and ACC, as well as reduced hepatic expression of FAS and HMGC, suggesting that lipogenesis was compromised. We also found robust evidence that treatment with IF significantly depleted infiltrating inflammatory cells (F4/80+ Kuffer cells and CD68+ macrophages ) and inflammatory cytokines release (TNFα and IL-6). Moreover, the anti-inflammation activity in IF-treated hepatic tissue correlated with down-regulation of TLR4 expression and NFκB transcription. In sum, these results suggest that IF might play a protective role in protecting against lipid metabolism disorder induced by a high-fat diet via inhibition of lipid production and inflammation in the liver.

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Publication details

The article was received on 21 Feb 2017, accepted on 02 Jul 2017 and first published on 04 Jul 2017


Article type: Paper
DOI: 10.1039/C7FO00290D
Citation: Food Funct., 2017, Accepted Manuscript
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    Isofraxidin, a coumarin component improves high-fat diet induced hepatic lipid homeostasis disorder and macrophage inflammation in mice

    J. Li, X. Li, Z. Li, L. Zhang, Y. Liu, S. Yin and H. Ding, Food Funct., 2017, Accepted Manuscript , DOI: 10.1039/C7FO00290D

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