title: By improving regional cortical blood flow, attenuating mitochondrial dysfunction and sequential apoptosis  galangin acts as a potential neuroprotective agent after  acute ischemic stroke.
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.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Shaojing
authors.initials: S
authors.lastname: Li
authors.forename: Chuanhong
authors.initials: C
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Defeng
authors.initials: D
authors.lastname: Li
authors.forename: Meihong
authors.initials: M
authors.lastname: Fu
authors.forename: Rixin
authors.initials: R
authors.lastname: Liang
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.forename: Hongjun
authors.initials: H
authors.lastname: Yang
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage*; D020441:Ginkgo biloba; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000096983:Ginkgo Extract
chemical_list: D053148:Caspase 3; D045304:Cytochromes c; D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C037032:galangin; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C499322:Parp1 protein, rat; C505410:Casp3 protein, rat