Anti-ischemic and anti-inflammatory activity of (S)-cis-verbenol.

(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.