Neuroprotective effect of 5,7,3',4',5'-pentahydroxy dihydroflavanol-3-O-(2''-O-galloyl)-beta-D-glucopyranoside, a polyphenolic compound in focal cerebral ischemia in rat.
Ischemia/reperfusion injury ends up in the cascade of excitotoxic stimulation of superoxide and nitric oxide formation leading to the generation of highly reactive products, including peroxinitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Several polyphenolic compounds scavenge the radicals and protect from injury. 5,7,3',4',5'-pentahydroxy dihdroflavanol-3-O-(2''-O-galloyl)-beta-d-glucopyranoside (AP1), a polyphenolic compound, isolated from Anogeissus pendula Edgew was tested for its neuroprotective effect in transient focal cerebral ischemia in rats. Transient focal cerebral ischemia was produced by middle cerebral artery occlusion for 2h for studying infarct volume, brain edema, apoptosis and oxidative stress. AP1 was tested for in vitro protection from glutamate and hydrogen peroxide-induced damage to Neuro-2a cells by MTT assay. It was also tested for its in vitro antioxidant, lipid peroxidation inhibition, NO scavenging and cyclooxygenase inhibitory activities. AP1 treatment (30 mg/kg i.p.) before reperfusion injury (0 h) significantly reduced the infarct volume, cerebral edema, number of apoptotic cells in penumbra and neurobehavioural abnormality score and lipid peroxidation, protein carbonyl levels and total thiols in brain. Increased catalase activity and NOx levels in ischemic animals were significantly reduced by AP1 treatment. AP1 (3 microg/ml) protected Neuro-2a cells to H2O2 and glutamate-induced damage. In in vitro studies, AP1 was found to possess reducing and NO scavenging activities. It also reduced lipid peroxidation and inhibited cyclooxygenase activity (cyclooxygenase-1 and cyclooxygenase-2). AP1 can be used as a neuroprotective agent in stroke as it reduced apoptosis and found to be a good antioxidant and anti-inflammatory compound.
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243 122 (U.P.), India.
Rathinam
R
ArunaDevi
Suman
S
Lata
Brijesh K
BK
Bhadoria
Vinod D
VD
Ramteke
Saurabh
S
Kumar
Palanisamy
P
Sankar
Dinesh
D
Kumar
Surendra K
SK
Tandan
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D018698:Glutamic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D059808:Polyphenols; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
C547089:5,7,3',4',5'-pentahydroxy-dihydroflavanol-3-O-(2'-O-galloyl)-beta-D-glucopyranoside; D000975:Antioxidants; D005419:Flavonoids; D005960:Glucosides; D018696:Neuroprotective Agents; D010636:Phenols; D059808:Polyphenols; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D011451:Prostaglandin-Endoperoxide Synthases