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Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism.

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收录情况： ◇ SCIE

作者：
Suguro Rinkiko[a,b] * ; Pang Xiao-Cong[c] * ; Yuan Zhong-Wen[a,d] * ; Chen Si-Yao[e] ; Zhu Yi-Zhun[a] ; Xie Ying[a] ;
机构： [a]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science & Technology, Taipa, Macau, China [b]Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China [c]Department of Pharmacy, Peking University First Hospital, Dahongluochang Street, Xicheng District, Beijing, 100034, China [d]Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China [e]Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road, Guangzhou, 510080, Guangdong, China
出处：
DOI： 10.1016/j.phrs.2019.104519
ISSN：

关键词： Silybin Tangeretin Lipid metabolism NASH

摘要：
Silybin (SB) is widely used to treat chronic liver diseases, especially this compound is much efficient for the treatments of alcoholic and non-alcoholic steatohepatitis (NASH). However, low bioavailability seriously limits wide-application of SB in biomedical niche. Prior to this study, we found that tangeretin (TG) could remarkably increase the bioavailability of SB by the inhibition of efflux transporters, which encourges us to therapeutical discovery of SB and TG combitional use against NASH. Here, we revealed that TG is capable of improving hepatic-protective activity of SB in mice with NASH by interfering liver oxidative stress, inflammation, and lipid accumulation. In addition, TG was observed to enhance the exposural level of SB in the plasma and liver of mice. Our metabolome assay confirmed that amino acid metabolism and lipid biosynthesis mostly accounted for combitional use of SB and TG to teat NASH in mice, basically biosynthesis of unsaturated fatty acids was mostly affected. Notably, significant inhibitions in fatty acid generating and transporting proteins such as G6PD, FABP4, LPL and CD36/FAT, and cholesterol metabolism enzyme CYP27A1 as well as nuclear transcription factors FXR, PPAR-γ, and LXR were illustrated to decipher therapeutic mechanisms of SB and TG against experimental NASH. Taken together, the strategy based combitional use of SB and TG has a potential-capacity to treat NASH. Copyright © 2019 Elsevier Ltd. All rights reserved.

基金：
This work was financially funded by The Science and Technology Development Fund, Macau SAR (File no. 003/2017/A1, 0067/2019/ A2)
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外文
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中科院(CAS)分区：
出版当年[2019]版：
大类 | 2 区 医学
小类 | 1 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 1 区 药学
JCR分区：
出版当年[2018]版：
Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

第一作者：
第一作者机构： [a]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science & Technology, Taipa, Macau, China [b]Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Suguro Rinkiko,Pang Xiao-Cong,Yuan Zhong-Wen,et al.Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism.[J].PHARMACOLOGICAL RESEARCH.2020,151:doi:10.1016/j.phrs.2019.104519.
APA：
Suguro Rinkiko,Pang Xiao-Cong,Yuan Zhong-Wen,Chen Si-Yao,Zhu Yi-Zhun&Xie Ying.(2020).Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism..PHARMACOLOGICAL RESEARCH,151,
MLA：
Suguro Rinkiko,et al."Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism.".PHARMACOLOGICAL RESEARCH 151.(2020)

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