Planta Med 2009; 75(2): 121-126
DOI: 10.1055/s-0028-1088368
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Scutellarin Against Cerebral Ischemia in Rats: Evidence for Inhibition of the Apoptosis-Inducing Factor Pathway

Hua-Feng Zhang1 , Xia-Min Hu1 , Lan-Xin Wang1 , Shi-Qiang Xu1 , Fan-Dian Zeng2
  • 1Department of Pharmacology, Medical College of Wuhan University of Science and Technology, Wuhan, P.R. China
  • 2Institute of Clinical Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, P.R. China.
Further Information

Publication History

Received: October 7, 2007 Revised: September 25, 2008

Accepted: October 2, 2008

Publication Date:
24 November 2008 (online)

Abstract

Scutellarin (Scu) is the major active principle (flavonoid) extracted from Erigeron breviscapus (Vant.) Hand-Mazz, a Chinese herbal medicine. In this paper, we investigated the effects of Scu on brain injury through the inhibition of AIF-mediated apoptosis induced by transient focal brain ischemia in rats. Rats were treated with Scu for 7 d and then subjected to cerebral ischemia/reperfusion (I/R) injury induced by a middle cerebral artery occlusion (MCAO). After 2 h of ischemia and 22 h of reperfusion, the infarct volume and the neurological deficit were determined by TTC staining and Longa’s score. In situ end-labeling of nuclear DNA fragments (TUNEL) was employed to determine the degree of DNA fragmentation. NAD content and PARP activity in brain homogenate were determined. The expression of AIF in the nucleus was analyzed by Western blot. The present study showed that Scu significantly reduced the infarct volume and ameliorated the neurological deficit. An increase in the number of TUNEL-positive cells and a decrease in the NAD level were also observed after 2 h of ischemia and 22 h of reperfusion. At the same time, Scu (50 and 75 mg kg−1, i. g.) treatment reversed brain NAD depletion and reduced DNA fragmentation. Scu also inhibited PARP overactivation and AIF translocation from the mitochondria to the nucleus following cerebral I/R. These findings suggested that the neuroprotective effects of Scu on brain ischemic injury-induced apoptosis might be associated with inhibition of PARP-dependent mitochondrial dysfunction and subsequent translocation of AIF.

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Xia-Min Hu

Wuhan University of Science and Technology

Wuhan 430080

People’s Republic of China

Phone: +86-27-6889-3640

Email: huxiaming@163.com

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