Baicalein and 12/15-lipoxygenase in the ischemic brain.
OBJECTIVE
The natural product baicalein is a specific inhibitor of 12/15-lipoxygenase, but it also has antioxidant properties. The current study was designed to test if the neuroprotective properties of baicalein are related to its lipoxygenase inhibition.


METHODS
The presence of 12/15-lipoxygenase in the ischemic mouse brain was demonstrated by immunohistochemistry. A mouse model of transient middle cerebral artery occlusion was used to study lipoxygenase-dependent protection of the ischemic brain by baicalein. Rat primary neurons were subjected to oxidative stress in the presence or absence of baicalein.


RESULTS
In a mouse model of transient middle cerebral artery occlusion, 12/15-lipoxygenase is increased in the peri-infarct area surrounding the primary infarction, predominantly in neurons. Oxidative toxicity in primary rat neurons is reduced by baicalein. C57Bl6J mice are protected against transient focal ischemia by intraperitoneal injection of baicalein, and a similar degree of protection is seen in 12/15-lipoxygenase knockout mice compared with wild-type mice. In contrast, the 12/15-LOX knockout mice are not further protected by baicalein.


CONCLUSIONS
Baicalein protects against ischemia/reperfusion injury by inhibiting the 12/15-lipoxygenase pathway to neuronal cell death.
van Leyen
Klaus
K
Stroke and Neurovascular Research Group, Department of Radiology, Massachusetts General Hospital, 149 13th St., R. 2401, Charlestown, MA 02129, USA. klaus_vanleyen@hms.harvard.edu
Kim
Hahn Young
HY
Lee
Seong-Ryong
SR
Jin
Guang
G
Arai
Ken
K
Lo
Eng H
EH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001092:Arachidonate 12-Lipoxygenase / Q000502:physiology; D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology*; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
C475064:12-15-lipoxygenase; D000975:Antioxidants; D044950:Flavanones; D016859:Lipoxygenase Inhibitors; C006680:baicalein; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase