Neurochem Res. 2013 Nov;38(11):2268-75. doi: 10.1007/s11064-013-1135-8. Epub 2013 Aug 29.

Hydroxysafflor yellow A protects against cerebral ischemia-reperfusion injury by anti-apoptotic effect through PI3K/Akt/GSK3β pathway in rat.

Chen L1, Xiang Y, Kong L, Zhang X, Sun B, Wei X, Liu H.

• 1Department of Pharmacology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.

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.

PMID:  23990223