Hydroxysafflor Yellow A Protects Against Cerebral Ischemia–Reperfusion Injury by Anti-apoptotic Effect Through PI3K/Akt/GSK3β Pathway in Rat

• Published in: Neurochemical research 2013-11, Vol.38 (11), p.2268-2275
• Main Authors: Chen, Lin, Xiang, Yanxiao, Kong, Lingjun, Zhang, Xiumei, Sun, Baozhu, Wei, Xinbing, Liu, Huiqing
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain Ischemia - prevention & control; Cell Biology; Chalcone - analogs & derivatives; Chalcone - therapeutic use; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Infarction, Middle Cerebral Artery - drug therapy; Male; Neurochemistry; Neurology; Neuroprotective Agents - pharmacology; Neurosciences; Original Paper; Phosphatidylinositol 3-Kinase - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Quinones - therapeutic use; Rats; Rats, Wistar; Reperfusion Injury - prevention & control; Signal Transduction - drug effects
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-013-1135-8

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.