Pharmacolog and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, China.
J Pharmacol Sci. 2010;113(4):395-403. doi: 10.1254/jphs.10041fp.
Hyperlipidemia is a major risk factor for cardiovascular diseases. In this study, we investigated the potential effects of cordycepin (3'-deoxyadenosine), a bioactive component of the fungus Cordyceps militaris, on hyperlipidemia. We found that in male Syrian golden hamsters fed a high-fat diet (HFD), daily administration of cordycepin effectively reduced the accumulation of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) and suppressed HFD-associated increases in relative retroperitoneal fat. It also increased the levels of phospho-AMP-activated protein kinase (AMPK) and phospho-acetyl-CoA carboxylase (phospho-ACC) in liver and retroperitoneal adipose tissues. In HepG2 cells, cordycepin stimulated robust concentration- and time-dependent AMPK activation that correlated with the activation of ACC and the suppression of lipid biosynthesis. However, pretreatment with compound C, a specific inhibitor of AMPK, substantially abolished the effects of cordycepin on AMPK activation and lipid biosynthesis inhibition. These results indicate that cordycepin prevents hyperlipidemia via activation of AMPK. Experiments on abnormal metabolic mice indicated that cordycepin can also improve insulin sensitivity effectively.
高脂血症是心血管疾病的一个主要危险因素。在这项研究中，我们研究了蛹虫草（真菌蛹虫草的一种生物活性成分）中的虫草素（3'-脱氧腺苷）对高脂血症的潜在影响。我们发现，在喂食高脂肪饮食（HFD）的雄性叙利亚金黄地鼠中，虫草素的每日给药可有效减少血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-c）的积累，并抑制 HFD 相关的相对腹膜后脂肪增加。它还增加了肝和腹膜后脂肪组织中磷酸化 AMP 激活的蛋白激酶（AMPK）和磷酸化乙酰辅酶 A 羧化酶（磷酸化 ACC）的水平。在 HepG2 细胞中，虫草素刺激了强大的浓度和时间依赖性的 AMPK 激活，与 ACC 的激活和脂质生物合成的抑制相关。然而，用 AMPK 的特异性抑制剂 compound C 预处理，可显著消除虫草素对 AMPK 激活和脂质生物合成抑制的作用。这些结果表明，虫草素通过激活 AMPK 来预防高脂血症。对代谢异常小鼠的实验表明，虫草素还能有效提高胰岛素敏感性。
