Acta Pharmacologica Sinica (2010) 31: 137–144; doi: 10.1038/aps.2009.196

Acta Pharmacologica Sinica (2010) 31: 137–144; doi: 10.1038/aps.2009.196

Original Article

Baicalin attenuates oxygen-glucose deprivation-induced injury by inhibiting oxidative stress-mediated 5-lipoxygenase activation in PC12 cells

Cheng-tan LI^{1, 2}, Wei-ping ZHANG¹, San-hua FANG¹, Yun-bi LU¹, Li-hui ZHANG², Ling-ling QI¹, Xue-qin HUANG¹, Xiao-jia HUANG¹, Er-qing WEI^{1, *}

¹Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China; ²Hangzhou Key Laboratory of Neurobiology and Department of Pharmacology, School of Basic Medicine, Hangzhou Normal University, Hangzhou 310036, China

Aim: To determine whether the flavonoid baicalin attenuates oxygen-glucose deprivation (OGD)-induced injury by inhibiting oxidative stress-mediated 5-lipoxygenase (5-LOX) activation in PC12 cells.

Methods: The effects of baicalin and the 5-LOX inhibitor zileuton on the changes induced by OGD/recovery or H₂O₂ (an exogenous reactive oxygen species [ROS]) in green fluorescent protein-5-LOX-transfected PC12 cells were compared.

Results: Both baicalin and zileuton attenuated OGD/recovery- and H₂O₂-induced injury and inhibited OGD/recovery-induced production of 5-LOX metabolites (cysteinyl leukotrienes) in a concentration-dependent manner. However, baicalin did not reduce baseline cysteinyl leukotriene levels. Baicalin also reduced OGD/recovery-induced ROS production and inhibited 5-LOX translocation to the nuclear envelope and p38 phosphorylation induced by OGD/recovery and H₂O₂. In contrast, zileuton did not show these effects.

Conclusion: Baicalin can inhibit 5-LOX activation after ischemic injury, which may partly result from inhibition of the ROS/p38 mitogen-activated protein kinase pathway.

Keywords: baicalin; 5-lipoxygenase; rat pheochromocytoma (PC12) cell; oxygen-glucose deprivation; reactive oxygen species; p38 mitogen-activated protein kinase

This study was supported by the National Natural Science Foundation of China, No 30672449 and No 30772561. We thank Professor CD Funk, the Center for Experimental Therapeutics and the Department of Pharmacology at the University of Pennsylvania, USA (now at the Department of Physiology, Queen’s University, Canada), for kindly providing the pEGFP/C2-5-LOX and pEGFP/C2 vectors.

* To whom correspondence should be addressed.
E-mail weieq2006@zju.edu.cn
Received 2009-10-22 Accepted 2009-12-03

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