Cordyceps mycelium has long been recognized as an important medicinal mushroom in China. Its pharmaceutical properties were recorded in the book “Ben-Cao-Bei-Yao,” edited by Wang Ang in 1694. Cordyceps mycelium has beneficial effects on the human body, which include immune, anti-tumor, anti-metastatic, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidemic, hypoglycemic, anti-aging, neuroprotective, and renoprotective effects (Paterson 2008; Zhou, Gong et al. 2009; Shin, Kwon et al. 2010). Cordyceps mycelium-derived natural products are comprised of complex components, including cordycepin derivatives, cordycepic acid, ergosterol, polysaccharides, and nucleosides (Li, Yang et al. 2006; Yue, Ye et al. 2013). Adenosine, cordycepin, cordycepic acid, and polysaccharides have been thought to be the main active ingredients, although this is still debated (Yue, Ye et al. 2013).

Cordyceps mycelium has been reported to function as an aphrodisiac (Bhattarai 1989), an analgesic (Koyama, Imaizumi et al. 1997), an immune modulator (Zhou, Gong et al. 2009), a free radical scavenger (Wang, Won et al. 2005), and an anti-cancer agent (Sun, Chia et al. 2005; Jin, Kim et al. 2008; Yoshikawa, Kunitomo et al. 2009). Because natural Cordyceps mycelium is rare and expensive, many scientists have examined its life cycle with the aim of developing techniques for the isolation and culture of fermentable strains.

Paecilomyces hepiali (PH) is a derivative of Cordyceps sinensis (CS), a fungus that has been shown to have anti-cancer and pro-apoptotic effects. This strain was one of the best known CS derivatives (Buenz, Bauer et al. 2005). Some studies have shown that PH can inhibit tumor proliferation, invasion, metastasis, and neovascularization; induce apoptosis; reverse drug resistance; and enhance immunity (Ng and Wang 2005; Wang, Won et al. 2005). Despite these reports on the inhibitory potential of PH on immune modulation, there have been no conclusive reports thus far on the mechanisms responsible for PH-mediated anti-inflammatory effects in macrophages.

Moreover, most of the aforementioned studies used only active ingredient extracts of mycelia. When the cultured mycelium was dissolved in water, most of the mycelium was precipitated. Only a small portion of the mycelium dissolved into the water, which is referred to as the extracted active ingredient of mycelium. Thus, the active ingredient portion was in a very highly concentrated form, relative to the total mycelium. However, for general applications of these mycelia, the water-soluble form was employed, not the highly concentrated form, as was the case for the experimental conditions.

Thus, in the present report, we examined the anti-inflammatory effects of CS mycelium (Paecilomyces hepiali, CBG-CS-2) using water-soluble fractions on murine macrophage Raw264.7 cells.