Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
Mar Drugs. 2017 Nov 14;15(11):358. doi: 10.3390/md15110358.
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 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.
Asperlin 是一种来源于海洋的天然产物，具有体外抗真菌和抗炎活性。在本研究中，我们从海洋 LZD4403 真菌中分离出 Asperlin，并研究了其在体外和体内的抗动脉粥样硬化作用。 Asperlin 可显著抑制脂多糖（LPS）但不抑制氧化型低密度脂蛋白（oxLDL）诱导的泡沫细胞形成，并促进 RAW264.7 巨噬细胞中的胆固醇流出。补充 Asperlin 还可抑制 LPS 诱导的 RAW264.7 巨噬细胞中促炎因子的产生，降低 iNOS、IL-1β 和 TNFα 的表达水平，增加 IL-10 和 IL-4 的表达，表明 M1/M2 巨噬细胞极化发生显著转变。在高脂肪饮食（HFD）喂养的 ApoE 小鼠体内实验中， Asperlin 口服给药 12 周可显著抑制主动脉中的动脉粥样硬化斑块形成，表现为主动脉扩张减少和动脉粥样硬化病变面积减小。Asperlin 还降低了 ApoE 动脉粥样硬化小鼠的血清促炎因子水平，但对血脂影响不大。这些结果表明，Asperlin 足以在体内预防动脉粥样硬化。它可能通过抑制炎症而不是改善血脂异常发挥抗动脉粥样硬化作用。
