SCHEDULED MAINTENANCE
Phenolic metabolites from mangrove-associated Penicillium pinophilum fungus with lipid-lowering effects†
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 μM 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 PPARγ, LXRα 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.
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