Asperlin Inhibits LPS-Evoked Foam Cell Formation and Prevents Atherosclerosis in ApoE-/- Mice.

Abstract

Asperlin is a marine-derived natural product with antifungal and anti-inflammatory activities in vitro. In the present study, we isolated asperlin from a marine Aspergillus versicolor LZD4403 fungus and investigated its anti-atherosclerotic effects in vitro and in vivo. Asperlin significantly inhibited lipopolysaccharides (LPS)- but not oxidated low-density lipoprotein (oxLDL)-evoked foam cell formation and promoted cholesterol efflux in RAW264.7 macrophages. Supplementation with asperlin also suppressed LPS-elicited production of pro-inflammatory factors in RAW264.7 macrophages, decreased the expression levels of iNOS, IL-1β and TNFα, and increased the expression of IL-10 and IL-4, indicating a remarkable shift in M1/M2 macrophages polarization. In vivo experiments in high-fat diet (HFD)-fed ApoE-/- mice showed that oral administration of asperlin for 12 weeks remarkably suppressed atherosclerotic plaque formation in the aorta, as revealed by the reduced aortic dilatation and decreased atherosclerotic lesion area. Asperlin also decreased serum levels of pro-inflammatory factors but showed little impact on blood lipids in ApoE-/- atherosclerotic mice. These results suggested that asperlin is adequate to prevent atherosclerosis in vivo. It may exert atheroprotective function through suppressing inflammation rather than ameliorating dyslipidemia.

• Authors: Yue Zhou, Ran Chen, Dong Liu, Chongming Wu, Peng Guo, Wenhan Lin
• Journal: Marine drugs (Mar Drugs) Vol. 15 Issue 11 (Nov 14 2017) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 29135917 (Publication Type: Journal Article)

Chemical References

• Apolipoproteins E
• Epoxy Compounds
• Interleukin-1beta
• Lipopolysaccharides
• Lipoproteins, LDL
• Pyrones
• Tumor Necrosis Factor-alpha
• oxidized low density lipoprotein
• asperlin
• Nitric Oxide Synthase Type II

Topics

• Animals
• Aorta (drug effects, metabolism)
• Apolipoproteins E (metabolism)
• Atherosclerosis (metabolism, prevention & control)
• Cell Line
• Diet, High-Fat (methods)
• Epoxy Compounds (pharmacology)
• Foam Cells (drug effects, metabolism)
• Inflammation (drug therapy, metabolism)
• Interleukin-1beta (metabolism)
• Lipopolysaccharides (pharmacology)
• Lipoproteins, LDL (metabolism)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nitric Oxide Synthase Type II (metabolism)
• Plaque, Atherosclerotic (metabolism, prevention & control)
• Pyrones (pharmacology)
• RAW 264.7 Cells
• Tumor Necrosis Factor-alpha (metabolism)