Integrated bioinformatics analysis of the anti-atherosclerotic mechanisms of the polysaccharide CM1 from Cordyceps militaris.

Cordyceps militaris is a well-known traditional Chinese medicine. Studies have demonstrated that the polysaccharides of C. militaris have various bioactivities. However, their mechanisms of action remain unclear. We previously purified a water-soluble polysaccharide CM1 from C. militaris and found that it has a cholesterol efflux improving capacity. This study further investigates the effect of CM1 in anti-atherosclerosis and its underlying mechanism in apolipoprotein E-deficient mice. Our data indicated that CM1 significantly decreased the total cholesterol and triglyceride in the plasma of mice, and decreased lipid deposition and formation of atherosclerotic plaque in a dose-dependent manner. Integrated bioinformatics analysis revealed that CM1 interacted with multiple signaling pathways, including those involved in lipid metabolism, inflammatory response, oxidoreductase activity and fluid shear stress, to exert its anti-atherosclerotic effect. Molecular technology analysis showed that CM1 enhanced the expression of proteins involved in lipid metabolism, reduced the expression of intercellular adhesion molecule-1 and tumor necrosis factor-α in the aorta, and decreased the content of oxidative products by enhancing the activities of antioxidant enzymes. Microarray analysis and biochemical data indicated that CM1 can improve lipid metabolism, reduce inflammation and oxidative stress. Taken together, CM1 could be used for the treatment of hyperlipidemia and atherosclerotic cardiovascular diseases. • The bioactive CM1 alleviated formation of atherosclerotic lesions in apoE −/− mice. • The underlying mechanisms was elucidated by integrated bioinformatics analysis. • The mechanisms of action of CM1 was further verified by other molecular methods. • These data explained the bioactivities of the polysaccharides from C. militaris. [ABSTRACT FROM AUTHOR]