Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 113, Issue 4, Pages 395-403Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.10041FP
Keywords
cordycepin; hyperlipidemia; AMP-activated protein kinase (AMPK); acetyl-CoA carboxylase (ACC); Cordyceps militaris
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Funding
- National ST Major Project [2009ZX09103-034, 2009ZX09303-003]
- National Natural Sciences Foundation of China (NSFC) [30873063, 30973527]
- Natural Sciences Foundation of Beijing [7092068, 7102115, 7102111]
- Youth Foundation of Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College [2006QZH01]
- National 973 Fundamental Project of China [2009CB523004]
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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 biosysthesis. However, pretreatment with compound C, a specific inhibitor of AMPK, substantially abolished the effects of cordycepin prevents hyperlipilemia via activation of AMPK. Experiment on abnormal metabolic mice indicated that cordycepin can also improve insulin sensitivity effectively
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