Effect of Cordyceps militaris extract and active constituents on metabolic parameters of obesity induced by high-fat diet in C58BL/6J mice

Ethnopharmacological relevance: Cordyceps species which is well-known as 'winter worm summer grass' has long been used as tonics and stimulants to enhance energy, exhibiting a potential for energy metabolism. Clinical trials have suggested their beneficial effect on lipid metabolic disorders such as hyperlipidemia. Materials and methods: The effect of Cordyceps militaris on metabolic parameters was investigated using C58BL/6J mice induced by high-fat diet (HFD). The effect was first determined by assessing the body and organ weight. For further investigation, sections of epididymal adipose tissue were stained with hematoxylin and eosin and the size of epididymal adipocyte was measured by Image analysis system. Fat accumulation in frozen liver sections was assessed by the Oil Red 0 staining and the plasma biochemical parameters were also assessed. Active constituents were characterized using chromatographic and spectroscopic analysis. Results: The administration of Cordyceps militaris extract (CE) at the dose of 100 mg/kg and 300 mg/kg reduced body weight gain and food efficiency ratio induced by HFD. The amount of epididymal fat and size of adipocytes were also decreased by CE treatment. In addition, liver weight and fat deposition in liver were dramatically reduced in CE-treated group. The treatment of CE also showed beneficial effects on plasma parameters related to lipid profiles. Further study for the characterization of active constituents of Cordyceps resulted in the isolation of two new compounds such as cordyrroles A (1) and B (7) together with 12 known compounds including pyrrole alkaloids and nucleotide derivatives. Among the isolated compounds, cordyrrole A significantly inhibited adipocyte differentiation and pancreatic lipase activity, whereas cordyrrole B was more effective at inhibiting pancreatic lipase. Cordycepin, a characteristic compound of Cordyceps militaris, decreased the rate of adipocyte differentiation. Conclusion: Treatment of CE inhibited HFD-induced metabolic disorders, mainly by improvement in metabolic parameters. As active constituents, pyrrole alkaloids and nucleotide derivatives were characterized. These results suggested that Cordyceps militaris might be beneficial for the treatment of metabolic disorders obesity through the combined actions of diverse constituents. (C) 2013 Elsevier Ireland Ltd. All rights reserved.This study was supported by a grant from the Korean Rural Development Administration (Agenda Program, PJ0067792010), and by Basic Science Research Program (2012-0008023) and Medical Research Center Program (2010-0029480) through the National Research Foundation of Korea