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.
Choi
In-Young
IY
Department of Neuroscience, College of Medicine, Korea University, Seoul, Republic of Korea.
Lim
Ji H
JH
Hwang
Sunyoung
S
Lee
Jae-Chul
JC
Cho
Geum-Sil
GS
Kim
Won-Ki
WK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D000081008:Bicyclic Monoterpenes; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D008297:Male; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D000081008:Bicyclic Monoterpenes; D016207:Cytokines; D039821:Monoterpenes; D017382:Reactive Oxygen Species; C009951:verbenol; D005947:Glucose; D010100:Oxygen