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Phenolic metabolites from mangrove-associated Penicillium pinophilum fungus with lipid-lowering effects

机译:来自红树丛相关的青霉素鸡蛋粒子的酚醛化合物,具有降脂效应

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摘要

Chemical examination of the mangrove-associated fungus Penicillium pinophilum (H608) resulted in the isolation of 16 phenolic metabolites, including a new metabolite, namely 5'-hydroxypenicillide (1). The structure of the new compound was determined by extensive spectroscopic analyses, in association with the Mosher method for configurational assignment. All compounds were tested for inhibitory effects against oleic acid (OA)-elicited lipid accumulation in HepG2 cells, while eight compounds (4, 7-8, and 11-15) exhibited inhibition toward lipid accumulation at a dose of 10 mu M with no cytotoxic effect. Further investigation revealed six compounds (4, and 11-15) that significantly suppressed intracellular total cholesterol (TC) and triglycerides (TGs). A real-time quantitative PCR indicated that compounds 4, 11, and 13-15 dramatically decreased the expression of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in association with up-regulation of carnitinepalmitoyl transferase-1 (CPT-1). In addition, seven compounds (4, 8, 11, and 13-16) significantly reduced oxidized low-density lipoprotein stimulated lipid accumulation in RAW264.7 cells. Mechanistic study revealed that compounds 14-16 remarkably decreased CD36 and SR-1 transcription, while compounds 4 and 15 dramatically up-regulated PPAR gamma, LXR alpha and ABCG1 to promote cholesterol efflux. This work provided a group of new chemical entities as promising leads for the development of hypolipidemic and anti-atherosclerotic agents.
机译:美洲红树相关真菌的化学检查 - Penicillium pinophilum(H608)导致16种酚醛代谢物分离,包括新的代谢物,即5'-羟基丙基(1)。通过广泛的光谱分析确定新化合物的结构,与用于配置分配的MoSher方法结合。在HepG2细胞中测试所有化合物对油酸(OA)的抑制作用(OA)的脂质积累,而8种化合物(4,7-8和11-15)表现出抑制脂质积累的剂量10μm,没有细胞毒性效应。进一步调查显示六种化合物(4,和11-15),该显著抑制细胞内的总胆固醇(TC)和甘油三酯(TGS)。实时定量PCR表明化合物4,11和13-15显着降低了脂肪酸合酶(FAS),乙酰基 - COA羧化酶(ACC)和3-羟基-3-甲基戊族-CoA还原酶(HMGR)的表达与肉氨基丙醛转移酶-1(CPT-1)的上调相关。此外,七种化合物(4,8,11和13-16)显着降低了Raw264.7细胞中的氧化低密度脂蛋白刺激的脂质积累。机理研究表明,化合物14-16显着降低CD36和SR-1的转录,而化合物4和15显着地上调PPARγ,LXRα和ABCG1促进胆固醇流出。这项工作提供了一组新化学实体,因为有前途的抗脂和抗动脉粥样硬化剂的发展。

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  • 来源
    《RSC Advances》 |2016年第26期|共10页
  • 作者单位

    Chinese Acad Med Sci Peking Union Med Coll Pharmacol &

    Toxicol Res Ctr Inst Med Plant Dev Beijing 100193 Peoples R China;

    Peking Univ State Key Lab Nat &

    Biomimet Drugs Beijing 100191 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Pharmacol &

    Toxicol Res Ctr Inst Med Plant Dev Beijing 100193 Peoples R China;

    Peking Univ State Key Lab Nat &

    Biomimet Drugs Beijing 100191 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Pharmacol &

    Toxicol Res Ctr Inst Med Plant Dev Beijing 100193 Peoples R China;

    Univ Dusseldorf Inst Pharmazeut Biol &

    Biotechnol Univ Str 1 Geb 26-23 D-40225 Dusseldorf Germany;

    Chinese Acad Med Sci Peking Union Med Coll Pharmacol &

    Toxicol Res Ctr Inst Med Plant Dev Beijing 100193 Peoples R China;

    Peking Univ State Key Lab Nat &

    Biomimet Drugs Beijing 100191 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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