Identification of a novel compound that stimulates intracellular calcium increase and CXCL8 production in human neutrophils from Schisandra chinensis.

Schisandra chinensis has been regarded as a useful material in the preventive or treatment of several human diseases. The study of the Schisandra chinensis' molecular identity has been prioritized because it has been found to regulate cellular responses. Here, we examined the effects from various extracts of Schisandra chinensis to monitor the relative intracellular calcium increase in human neutrophils. We identified an active molecule and structural configuration of a new active compound (alpha-iso-cubebene), based on the discovery of a cubebene backbone using NMR, MS, and CD spectral data. In terms of its functional aspect, we observed that alpha-iso-cubebene strongly stimulated CXCL8 production in human neutrophils. Also, alpha-iso-cubebene-induced CXCL8 production was almost completely inhibited by the calcium chelator, EGTA, thus highlighting the role of calcium signaling in the process. Taken together, our results demonstrate that alpha-iso-cubebene is a novel natural compound which stimulates intracellular calcium signaling and CXCL8 production. As a result, alpha-iso-cubebene should be useful for the development of an immune-modulating agent.