Baicalein is neuroprotective in rat MCAO model: role of 12/15-lipoxygenase, mitogen-activated protein kinase and cytosolic phospholipase A2

Pharmacol Biochem Behav. 2010 Oct;96(4):469-75. doi: 10.1016/j.pbb.2010.07.007. Epub 2010 Jul 14.

Abstract

Inflammatory damage and oxidative stress play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Baicalein, isolated from the traditional Chinese herbal medicine Huangqin, is an antioxidant and anti-inflammatory agent on one hand and a lipoxygenase inhibitor on the other hand. However, little is known regarding the mechanism of baicalein's neuroprotection in ischemic stroke. We therefore investigated the potential neuroprotective effects of baicalein and explored the underlying mechanisms. Male, Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and baicalein was administered intravenously immediately after cerebral ischemia. At 24h after MCAO neurological deficit, brain water content and infarct sizes were measured. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to analyse the expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK) and cytosolic phospholipase A2 (cPLA2) at gene and protein levels in ischemic brain cortex. The results showed that baicalein improved neurological deficit, reduced brain water content and infarct sizes, and downregulated the overexpression of 12/15-LOX, p38 MAPK and cPLA2 typically seen with MCAO. The results indicated that baicalein protected the brain from damage caused by MCAO, and this effect may be through downregulation of 12/15-LOX, p38 MAPK and cPLA2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / genetics
  • Arachidonate 12-Lipoxygenase / metabolism*
  • Arachidonate 15-Lipoxygenase / genetics
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Base Sequence
  • Blotting, Western
  • Brain Edema / prevention & control
  • Cytosol / enzymology*
  • DNA Primers
  • Flavanones / pharmacology*
  • Immunohistochemistry
  • Infarction, Middle Cerebral Artery / enzymology
  • Infarction, Middle Cerebral Artery / prevention & control*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Phospholipases A2 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • 12-15-lipoxygenase
  • DNA Primers
  • Flavanones
  • Neuroprotective Agents
  • RNA, Messenger
  • baicalein
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Mitogen-Activated Protein Kinases
  • Phospholipases A2