ABSTRACT
Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague-Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both and , which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially the AKT/FOXO3a/BIM pathway.
ABSTRACT
Aim To investigate the effects of diterpene ginkgolides meglumine injection (DGMI ) on amino acids and monoamine neurotransmitters in rats with cerebral ischemia/reperfusion injury.Methods In-traluminal suture was applied to establish middle cere-bral artery occlusion (MCAO/R)model with ischemia for 1.5 h and reperfusion for 24 h.After the adminis-tration of DGMI (i.v.),the levels of amino acid and monoamine neurotransmitters in brain tissue were de-tected through HPLC-ECD.Results DGMI down-reg-ulated the concentrations of aspartic acid, glutamic acid,glycine and γ-aminobutyric acid which were in-creased in MCAO/R group.DGMI also reduced the levels of norepinephrine epinephrine,glyoxylic acid, serotonin and 5-HIAA in cortex and hippocampus,and increased adrenaline content compared to the model group.Conclusion DGMI exhibits a protective role in rats with cerebral ischemia /reperfusion injury through regulating amino acids and monoamine neuro-transmitters.