Neuroprotective effect of hydroxy safflor yellow A against cerebral ischemia-reperfusion injury in rats: putative role of mPTP.
BACKGROUND
Hydroxy safflor yellow A (HSYA) has been translated clinically for cardiovascular diseases. HSYA is also greatly acknowledged for its protective effects against cerebral ischemic-reperfusion (I/R) injury. Although the precise mechanism of cerebral I/R injury is not fully understood, oxygen-derived free radicals and mitochondrial permeability transition pore (mPTP) opening during I/R injury are widely recognized as an important contributor to neuronal injury. Thus, we speculated that the neuroprotective effects of HSYA against cerebral I/R injury may be associated with mPTP modulation.


METHODS
Induction of I/R injury was achieved by 60 min of middle cerebral artery occlusion, followed by reperfusion for 24 h. For behavior and cognitive assessment, neurological scoring (NSS), rotarod, and Y-maze task were performed. Oxidative damage was measured in terms of markers such as malondialdehyde, reduced glutathione, and catalase levels and cerebral infarct volumes were quantified using 2,3,5-triphenyl tetrazolinium chloride staining. I/R injury-induced inflammation was determined using tumor necrosis factor-α (TNF-α) levels.


RESULTS
Animals exposed to I/R injury showed neurological severity, functional and cognitive disability, elevated oxidative markers, and TNF-α levels along with large infarct volumes. HSYA treatment during onset of reperfusion ameliorated performance in NSS, rotarod and Y-maze attenuated oxidative damage, TNF-α levels, and infarction rate. However, treatment with carboxyatractyloside, an mPTP opener, 20 min before HSYA, attenuated the protective effect of HSYA.


CONCLUSIONS
Our study confirmed that protective effect of HSYA may be conferred through its free radical scavenger action followed by inhibiting the opening of mPTP during reperfusion and HSYA might act as a promising therapeutic agent against cerebral I/R injury.
Sruthi
S
Ramagiri
Rajeev
R
Taliyan
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016166:Free Radical Scavengers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha; C085278:hydroxysafflor yellow A; D002599:Chalcone