title: Hydroxysafflor yellow A protects against cerebral ischemia-reperfusion injury by anti-apoptotic effect through PI3K/Akt/GSK3β pathway in rat.
abstract: Hydroxysafflor yellow A (HSYA) is the major active chemical component of the flower of the safflower plant, Carthamus tinctorius L. Previously, its neuroprotection against cerebral ischemia-reperfusion (I/R) injury was reported by anti-oxidant action and suppression of thrombin generation. Here, we investigate the role of HSYA in cerebral I/R-mediated apoptosis and possible signaling pathways. Male Wistar rats were subjected to transient middle cerebral artery occlusion for 2 h, followed by 24 h reperfusion. HSYA was administered via tail-vein injection just 15 min after occlusion. The number of apoptotic cells was measured by TUNEL assay, apoptosis-related proteins Bcl-2, Bax and the phosphorylation levels of Akt and GSK3β in ischemic penumbra were assayed by western blot. The results showed that administration of HSYA at the doses of 4 and 8 mg/kg significantly inhibited the apoptosis by decreasing the number of apoptotic cells and increasing the Bcl-2/Bax ratio in rats subjected to I/R injury. Simultaneously, HSYA treatment markedly increased the phosphorylations of Akt and GSK3β. Blockade of PI3K activity by wortmannin dramatically abolished its anti-apoptotic effect and lowered both Akt and GSK3β phosphorylation levels. Taken together, these results suggest that HSYA protects against cerebral I/R injury partly by reducing apoptosis via PI3K/Akt/GSK3β signaling pathway.
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Yanxiao
authors.initials: Y
authors.lastname: Xiang
authors.forename: Lingjun
authors.initials: L
authors.lastname: Kong
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Baozhu
authors.initials: B
authors.lastname: Sun
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000517:prevention & control*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011809:Quinones / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D011809:Quinones; D051028:bcl-2-Associated X Protein; C085278:hydroxysafflor yellow A; D002599:Chalcone; D058539:Phosphatidylinositol 3-Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3