| Title | Phenolic metabolites from mangrove-associated Penicillium pinophilum fungus with lipid-lowering effects |
| Authors | Wu, Chongming Zhao, Yang Chen, Ran Liu, Dong Liu, Mingyue Proksch, Peter Guo, Peng Lin, Wenhan |
| Affiliation | 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. 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. Lin, WH (reprint author), Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. |
| Keywords | DIPHENYL ETHER DERIVATIVES CHOLESTEROL EFFLUX STATIN THERAPY FOAM CELLS APOA-I ATHEROSCLEROSIS ABCA1 ABCG1 HDL PROGRESSION |
| Issue Date | 2016 |
| Publisher | RSC ADVANCES |
| Citation | RSC ADVANCES.2016,6,(26),21969-21978. |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/437912 |
| ISSN | 2046-2069 |
| DOI | 10.1039/c6ra00033a |
| Indexed | SCI(E) EI |
| Appears in Collections: | 天然药物与仿生药物国家重点实验室 |
