title: Punicalagin attenuated cerebral ischemia-reperfusion insult via inhibition of proinflammatory cytokines, up-regulation of Bcl-2, down-regulation of Bax, and caspase-3.
abstract: Punicalagin (PG) is a hydrolysable tannin compound found in Punica granatum L. The purpose of the present work is to explore the neuroprotective mechanism of PG against ischemia-reperfusion (I/R) injury in rat model of middle cerebral artery occlusion (MCAO). Rats were randomly divided into sham, MCAO, and PG-treated groups. PG (15 and 30 mg/kg), the vehicle was administered orally for 7 days prior to MCAO. Rats were anesthetised with ketamine (100 mg/kg/im), xylazine (10 mg/kg/im) and subjected to 2 h occlusion and 22 h reperfusion. The effects of PG on behavioral deficit and infarct volume, the levels of glutamate and calcium as well as the levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were evaluated. Moreover, the expressions of caspase-3, Bcl-2, and Bax were detected by Western blotting. As compared with MCAO group, PG-treated rats showed dose-dependent reduction in infarct volume and substantial improvement in behavioral deficit. The levels of glutamate, calcium, TNF-α, IL-1β, and IL-6 were restored significantly. The Western blotting results revealed that the expression of Bcl-2 was up-regulated and that of caspase-3, Bax were down-regulated when exposed to PG. From our results, it can be concluded that PG showed an ameliorative effect against cerebral I/R injury in rats through its anti-inflammatory, antioxidant actions besides it inhibits excitotoxicity. It also suppresses apoptosis through regulating, Bcl-2, caspase-3, and Bax protein expressions, perhaps another mechanism by which PG employs its neuroprotective action.
authors.affiliation: Division of Pharmacology Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati, 517502, Andhra Pradesh, India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Yaidikar
authors.forename: Santhrani
authors.initials: S
authors.lastname: Thakur
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D053580:Muscle Strength; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494828:Bax protein, rat; D016207:Cytokines; D047348:Hydrolyzable Tannins; D018836:Inflammation Mediators; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C115642:punicalagin; C505410:Casp3 protein, rat; D053148:Caspase 3