Hydroxysafflor Yellow A Protects PC12 Cells Against the Apoptosis Induced by Oxygen and Glucose Deprivation

Abstract

Hydroxysafflor yellow A (HSYA) was reported neuroprotective under several ischemic models in vivo. In this study, the direct effect of HSYA against oxygen-glucose deprivation (OGD) inducing acute neuronal injury and the underling mechanisms in vitro were investigated. Four-hour oxygen and glucose deprivation (OGD) followed by 20 h reperfusion (adding back oxygen and glucose, OGD-R) was used to induce in vitro ischemia reperfusion injury in differentiated rat pheochromocytoma PC12 cells. HSYA (1, 10, and 100 μmol/l) was added to the cultures 30 min prior to the ischemic insult and was present during OGD and reoxygenation phases. The survival rate of PC12 cells was detected by MTT assay. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) activity were elevated by biochemical method. Hoechst 33258 staining and flow cytometric analysis were used to detect apoptosis; western blotting was used to detect the expression of Bcl-2, Bax, and Cytochrome C protein. The activity of caspase-3 was assessed by colorimetry. HSYA concentration-dependently attenuated neuronal damage with characteristics of increasing injured neuronal absorbance of MTT, decreasing cell apoptosis, and antagonizing decreases in SOD activity and increase in MDA level induced by OGD-R. Moreover, the down-regulation of Bcl-2, up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol and the consequent activation of caspase-3 were reversed by HSYA in a dose-dependent manner. These results suggest that apoptosis is an important characteristic of OGD-R-induced PC 12 death and that treatment of PC12 cells with HSYA can block OGD-R-induced apoptosis through suppression of intracellular oxidative stress and mitochondria dependent caspase cascade.

Brusatol Protects HepG2 Cells against Oxygen-Glucose Deprivation-Induced Injury via Inhibiting Mitochondrial Reactive Oxygen Species-Induced Oxidative Stress

“…It is widely reported that ROS directly acts on phospholipids to induce lipid peroxidation and produce MDA [20]. Therefore, MDA is a marker of lipid peroxidation and an end product of oxidative damage [21,22]. As expected, we found that OGD-R induced significant oxidative injury in HepG2 cells, which was manifested by a marked increase in MDA level.…”

HSYA alleviates secondary neuronal death through attenuating oxidative stress, inflammatory response, and neural apoptosis in SD rat spinal cord compression injury

“…Studies also reported that HSYA protects human umbilical vein endothelial cells against hypoxic injury by inhibiting cell apoptosis [44, 45]. Our previous in vitro [46] study demonstrated that HSYA can block oxygen and glucose deprivation followed by reperfusion (OGD-R) induced pc-12 apoptosis through suppression of intracellular oxidative stress and mitochondria-dependent caspase cascade. In the present in vivo study, we discovered that HSYA treatment significantly improved hindlimb motor disturbances after SCI.…”

Inhibitory Effects of Hydroxysafflor Yellow A on the Formation of Advanced Glycation End Products <i>in Vitro</i>

“…25,26) It has been reported that HSYA exhibits antioxidative effects, alleviates oxidative stress. 19,27) In the rat brain, HSYA inhibits the opening of mitochondrial permeability transition pore by a free radical scavenging action. 28) Thus, it would be of great interest to identify the inhibitory effects of HSYA in protein glycation.…”