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Vascular endothelial growth factor (VEGF) is well recognized as an essential component of angiogenesis and the increased proliferation and migration of endothelial cells. Bone marrow-derived endothelial progenitor cells (EPCs) are involved in VEGF-induced vessel formation during physiological and pathological states. Soya-cerebroside, an extract from Cordyceps militaris, reduces synovial inflammation and prevents cartilage damage in an osteoarthritis model. However, the role of soya-cerebroside in VEGF-regulated EPC angiogenesis is uncertain. Records from the Oncomine database demonstrate higher levels of VEGF in cancerous tissue compared with normal tissue. This study describes VEGF-induced promotion of EPC-associated angiogenesis in vivo and how the treatment of EPCs with soya-cerebroside inhibited VEGF-facilitated migration and tube formation. The study evidence shows that the c-Src, FAK and Runx2 signalling pathways are involved in the inhibitory effects of soya-cerebroside. This novel agent may therefore be used to inhibit EPC-associated angiogenesis.

Rheumatoid arthritis (RA) is characterised by the infiltration of a number of proinflammatory cytokines into synovial fluid. Soya-cerebroside, an extract from Cordyceps militaris, inhibits synovial inflammation and reduces cartilage damage in an osteoarthritis model, although the role of soya-cerebroside in inflammatory cytokine expression in RA is uncertain. In this study, Gene Expression Omnibus (GEO) database records revealed higher levels of interleukin (IL)-1β, IL-6 and IL-8 in RA tissue compared with normal tissue. Elevated levels of these inflammatory cytokines were also higher in mice with collagen-induced arthritis (CIA) than in control mice. Soya-cerebroside effectively inhibited IL-1β, IL-6 and IL-8 expression in RA synovial fibroblasts, apparently by inhibiting the ERK, NF-κB and AP-1 signalling pathways. This anti-inflammatory agent shows promise for the treatment of RA.

The recruitment of bone marrow-derived endothelial progenitor cells (EPCs) facilitates physiological and pathological processes involved in new blood vessel synthesis. Glucocerebroside, an extract of Cordyceps militaris, inhibits inflammatory cytokine production and monocyte migration, although its anti-angiogenic properties in human EPCs has remained largely unknown up until now. We describe how glucocerebroside reduces migration as well as tube formation induced by vascular endothelial growth factor (VEGF) stimulation in human EPCs, without affecting cell viability. This inhibitory effect was achieved through the focal adhesion kinase (FAK)/c-Src pathways. We also found that glucocerebroside reduced VEGF-promoted upregulation of the transcription factor Runx2 in the EPCs. The in vivo chick embryo chorioallantoic membrane model demonstrated that glucocerebroside reduces new vessel formation. Our investigation is the first to show that glucocerebroside reduces angiogenesis in human EPCs and to describe the underlying mechanisms. Further investigations are needed to examine the effects of glucocerebroside in other angiogenesis-related disorders.