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Cordyceps militaris is a parasitic edible fungus and has been used as tonics for centuries. Polysaccharides are a major water-soluble component of C. militaris. Recently, C. militaris-derived polysaccharides have been given much attention due to their various actions including antioxidant, anti-inflammatory, anti-tumor, anti-hyperlipidemic, anti-diabetic, anti-atherosclerotic, and immunomodulatory effects. These bioactivities are determined by the various structural characteristics of polysaccharides including monosaccharide composition, molecular weight, and glycosidic linkage. The widespread use of advanced analytical analysis tools has greatly improved the elucidation of the structural characteristics of C. militaris-derived polysaccharides. However, the methods for polysaccharide structural characterization and the latest findings related to C. militaris-derived polysaccharides, especially the potential structure-activity relationship, have not been well-summarized in recent reviews of the literature. This review will discuss the methods used in the elucidation of the structure of polysaccharides and structural characteristics as well as the signaling pathways modulated by C. militaris-derived polysaccharides. This article provides information useful for the development of C. militaris-derived polysaccharides as well as for investigating other medicinal polysaccharides.

Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-β-D-Glcp and (1→2)-α-D-Manp glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR((-/-)) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR((−/−)) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis.

BACKGROUND: Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. METHODS: After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 μg/mL) on inhibiting adipocyte differentiation was investigated in vitro. RESULTS: CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR((+/−)) hamsters, which have a human-like lipid profile. After 5 months' administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation. CONCLUSIONS: The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-021-01606-6.