hydroxysafflor-yellow-a and Ischemic-Attack--Transient

Hydroxysafflor yellow A (HSYA) is the main component of the safflower yellow pigments, the aqueous extract of safflower florets. We report here an experimental study for evaluating HSYA for their neuroprotective qualities on rats subjected to middle cerebral artery occlusion (60 min) and reperfusion (24h), an experimental model in which excessive production of reactive oxygen and nitrogen species has been found. In our data, biochemical analysis of tissue proteins showed that cerebral ischemia/reperfusion (I/R) injury resulted in significant elevation of carbonyl groups and nitrotyrosine in the brain of I/R in comparison to sham controls, indicating the occurrence of oxidative/nitrative modification to brain proteins. HSYA-treatment (1, 5 and 10mg/kg) inhibited I/R-induced protein oxidation and nitration. 12/15-Lipoxygenase (12/15-LOX), the enzyme implicated in oxidative stress of cerebral I/R, displayed overexpression in I/R rats. Elevated 12/15-LOX activity, estimated by the level of its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE), was also induced by the challenge of cerebral I/R. Administration of HSYA 1, 5 and 10mg/kg reduced the upregulation of 12/15-LOX expression and activity in a dose-dependent manner. Moreover, the increase in blood-brain barrier (BBB) permeability evaluated by IgG leakage, Evans blue extravasation, and brain water content, respectively, was markedly alleviated by HSYA, indicating its protection against BBB disruption and brain edema following I/R insult. Taken together, these results demonstrate the neuroprotective properties of HSYA, which may be at least in part due to its potential to reduce protein oxidation and nitration, inhibit the upregulation of 12/15-LOX, and attenuate BBB breakdown.

Topics: Animals; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Blood-Brain Barrier; Blotting, Western; Chalcone; Disease Models, Animal; Fluorescent Antibody Technique; Ischemic Attack, Transient; Male; Neuroprotective Agents; Oxidation-Reduction; Oxidative Stress; Quinones; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Previous data demonstrated that hydroxysafflor yellow A (HSYA), a yellow color pigments extracted from the safflower, was an effective agent against focal cerebral ischemia. In the present study we demonstrated that HSYA prevented the injury in cultured cerebral cortical neurons induced by oxygen-glucose deprivation and increased the cell viability, as shown by the inhibition of both LDH and NO efflux. Further, HSYA administered orally 3 d before middle cerebral artery occlusion has the capacity to reduce cerebral infarct size and edema after 2 h cerebral ischemia followed by 24 h reperfusion in rats, and to significantly improve neurological behavior scores. Mean while, treatment with HSYA significantly decreased both mRNA and protein levels of IL-1beta, TNF-alpha in ischemic brain tissue. These results suggested that the protection of HSYA results from, at least in part, suppression of inflammatory responses following focal ischemia reperfusion.

Topics: Animals; Behavior, Animal; Blotting, Western; Brain Edema; Cell Hypoxia; Cells, Cultured; Chalcone; Female; Glucose; Indicators and Reagents; Inflammation; Interleukin-1beta; Ischemic Attack, Transient; L-Lactate Dehydrogenase; Neurons; Neuroprotective Agents; Nitric Oxide; Pregnancy; Quinones; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha

The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on brain injury after focal cerebral ischemia reperfusion, and to determine the possible mechanism. Behavioral tests were used to evaluate the damage to central nervous system. The infarct volume of brain was assessed in brain slices stained with 2% solution of 2,3,5-triphenyl tetrazolium chloride (TTC). Adult male Wistar rats were subjected to 2h of middle cerebral artery occlusion and 24h of reperfusion. Spectrophotometric assay was used to determine the content of malondialdehyde (MDA), and the activity of total antioxidative capability (T-AOC) and superoxide dismutase (SOD). The results showed that treatment with HSYA (2, 4, 8 mg/kg, i.v.) significantly decreased neurological deficit scores and reduced the percentage of infarction in the ipsilateral hemisphere compared with the model group. At the same time, HSYA treatment significantly attenuated the elevation of MDA content, the decrease in SOD activity, and the T-AOC in the ipsilateral hemisphere and serum. All of these findings suggest that HSYA might provide neuroprotection against cerebral ischemia/reperfusion injury through its antioxidant action.

Topics: Animals; Antioxidants; Brain; Cerebral Infarction; Chalcone; Disease Models, Animal; Free Radical Scavengers; Ischemic Attack, Transient; Malondialdehyde; Molecular Structure; Neuroprotective Agents; Oxidative Stress; Quinones; Rats; Reperfusion Injury; Superoxide Dismutase; Treatment Outcome