(S)-cis-
verbenol, a natural metabolite from (-)-
alpha-pinene of host pine tree, has been suggested to have anti-ischemic activity. However, the exact mechanism for the anti-ischemic activity of (S)-cis-
verbenol remains unclear yet. In the present study, (S)-cis-
verbenol reduced cerebral ischemic injury caused by 1.5-h
middle cerebral artery occlusion followed by 24-h reperfusion. Furthermore, (S)-cis-
verbenol significantly prevented neuronal cell death caused by
oxygen-
glucose deprivation (OGD, 1 h) and subsequent re-oxygenation (5 h). While (S)-cis-
verbenol did not inhibit the
NMDA-stimulated
calcium influx, it reduced the intracellular level of
reactive oxygen species (ROS) elevated by OGD/re-oxygenation. ORAC assay indicated that (S)-cis-
verbenol potently eliminated peroxyl radicals. In DPPH and DHR123 fluorescence assays, however, (S)-cis-
verbenol did not show a direct ROS scavenging effect. Furthermore, (S)-cis-
verbenol reduced the expression levels of pro-inflammatory
cytokines in ischemic brain and immunostimulated glial cells. The present results indicate that (S)-cis-
verbenol may be a useful therapeutic agent due to its anti-oxidative and anti-inflammatory activities.