Molecules 2012, 17(11), 13403-13423; doi:10.3390/molecules171113403
Article

By Improving Regional Cortical Blood Flow, Attenuating Mitochondrial Dysfunction and Sequential Apoptosis Galangin Acts as a Potential Neuroprotective Agent after Acute Ischemic Stroke

1 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China 2 Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China 3 College of Pharmaceutical Science, Hebei University, Baoding, Hebei 071002, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 19 October 2012; in revised form: 31 October 2012 / Accepted: 6 November 2012 / Published: 9 November 2012
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Abstract: Ischemic stroke is a devastating disease with a complex pathophysiology. Galangin is a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, which has been widely used as an antioxidant agent. However, its effects against ischemic stroke have not been reported and its related neuroprotective mechanism has not really been explored. In this study, neurological behavior, cerebral infarct volumes and the improvement of the regional cortical blood flow (rCBF) were used to evaluate the therapeutic effect of galangin in rats impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Furthermore, the determination of mitochondrial function and Western blot of apoptosis-related proteins were performed to interpret the neuroprotective mechanism of galangin. The results showed that galangin alleviated the neurologic impairments, reduced cerebral infarct at 24 h after MCAO and exerted a protective effect on the mitochondria with decreased production of mitochondrial reactive oxygen species (ROS). These effects were consistent with improvements in the membrane potential level (Dym), membrane fluidity, and degree of mitochondrial swelling in a dose-dependent manner. Moreover, galangin significantly improved the reduced rCBF after MCAO. Western blot analysis revealed that galangin also inhibited apoptosis in a dose-dependent manner concomitant with the up-regulation of Bcl-2 expression, down-regulation of Bax expression and the Bax/Bcl-2 ratio, a reduction in cytochrome c release from the mitochondria to the cytosol, the reduced expression of activated caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP). All these data in this study demonstrated that galangin might have therapeutic potential for ischemic stroke and play its protective role through the improvement in rCBF, mitochondrial protection and inhibiting caspase-dependent mitochondrial cell death pathway for the first time.
Keywords: galangin; mitochondria; cerebral ischemia

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MDPI and ACS Style

Li, S.; Wu, C.; Zhu, L.; Gao, J.; Fang, J.; Li, D.; Fu, M.; Liang, R.; Wang, L.; Cheng, M.; Yang, H. By Improving Regional Cortical Blood Flow, Attenuating Mitochondrial Dysfunction and Sequential Apoptosis Galangin Acts as a Potential Neuroprotective Agent after Acute Ischemic Stroke. Molecules 2012, 17, 13403-13423.

AMA Style

Li S, Wu C, Zhu L, Gao J, Fang J, Li D, Fu M, Liang R, Wang L, Cheng M, Yang H. By Improving Regional Cortical Blood Flow, Attenuating Mitochondrial Dysfunction and Sequential Apoptosis Galangin Acts as a Potential Neuroprotective Agent after Acute Ischemic Stroke. Molecules. 2012; 17(11):13403-13423.

Chicago/Turabian Style

Li, Shaojing; Wu, Chuanhong; Zhu, Li; Gao, Jian; Fang, Jing; Li, Defeng; Fu, Meihong; Liang, Rixin; Wang, Lan; Cheng, Ming; Yang, Hongjun. 2012. "By Improving Regional Cortical Blood Flow, Attenuating Mitochondrial Dysfunction and Sequential Apoptosis Galangin Acts as a Potential Neuroprotective Agent after Acute Ischemic Stroke." Molecules 17, no. 11: 13403-13423.

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