PMID- 27840933 OWN - NLM STAT- MEDLINE DCOM- 20170407 LR - 20170407 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 14 IP - 6 DP - 2016 Dec TI - Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats. PG - 5408-5414 LID - 10.3892/mmr.2016.5919 [doi] AB - A recent study reported that nobiletin is an active ingredient in Fructus Aurantii immaturus and Pericarpium Citri Reticulatae, which may be capable of preventing ischemic stroke. Therefore, the present study aimed to determine the neuroprotective effects of nobiletin, and to evaluate whether it could ameliorate isoflurane‑induced cognitive impairment via antioxidant, anti‑inflammatory and anti‑apoptotic effects in aging rats. Male Sprague‑Dawley rats (age, 18 months) were used to analyze the neuroprotective effects of nobiletin. Morris water maze test was used to determine cognitive competence. Enzyme‑linked immunosorbent assay and western blot analysis were also used to quantify nuclear factor‑kappaB, tumor necrosis factor (TNF)‑alpha, IL‑1beta, IL‑6, glutathione, (GSH), GSH‑peroxidase, superoxide dismutase and malondialdehyde concentration and relevant protein expression levels Cognitive competence was increased in isoflurane-treated rats following treatment with nobiletin. In addition, as expected, nobiletin exerted antioxidant, anti-inflammatory and anti‑apoptotic effects on isoflurane‑induced cognitive impairment in aging rats. Treatment with nobiletin induced the activation of phosphorylated (p)‑Akt, p‑cAMP response element binding protein (CREB) and brain‑derived neurotrophic factor (BDNF) protein expression and reduced the levels of B‑cell lymphoma 2‑associated X protein (Bax) in isoflurane‑induced rats. In conclusion, the present study demonstrated that nobiletin may ameliorate isoflurane-induced cognitive impairment through antioxidant, anti‑inflammatory and anti‑apoptotic effects via modulation of Akt, Bax, p‑CREB and BDNF in aging rats. These findings provide support for the molecular mechanisms underlying the effects of nobiletin treatment on isoflurane-induced damage. FAU - Bi, Junying AU - Bi J AD - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China. FAU - Zhang, Haiyan AU - Zhang H AD - Gynaecology Ward‑1, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China. FAU - Lu, Jing AU - Lu J AD - Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China. FAU - Lei, Weifu AU - Lei W AD - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China. LA - eng PT - Journal Article DEP - 20161101 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Cytokines) RN - 0 (Flavones) RN - 0 (Inflammation Mediators) RN - 0 (bcl-2-Associated X Protein) RN - CYS9AKD70P (Isoflurane) RN - D65ILJ7WLY (nobiletin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Aging/*metabolism/psychology MH - Animals MH - Anti-Inflammatory Agents/chemistry/*pharmacology MH - Antioxidants/chemistry/*pharmacology MH - Apoptosis/*drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cognitive Dysfunction/*chemically induced/drug therapy/*metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Cytokines/metabolism MH - Flavones/chemistry/*pharmacology MH - Inflammation Mediators MH - Isoflurane/*adverse effects MH - Male MH - Maze Learning/drug effects MH - Memory/drug effects MH - Oxidation-Reduction/drug effects MH - Oxidative Stress/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - bcl-2-Associated X Protein/metabolism EDAT- 2016/11/15 06:00 MHDA- 2017/04/08 06:00 CRDT- 2016/11/15 06:00 PHST- 2015/08/07 00:00 [received] PHST- 2016/08/22 00:00 [accepted] PHST- 2016/11/15 06:00 [pubmed] PHST- 2017/04/08 06:00 [medline] PHST- 2016/11/15 06:00 [entrez] AID - 10.3892/mmr.2016.5919 [doi] PST - ppublish SO - Mol Med Rep. 2016 Dec;14(6):5408-5414. doi: 10.3892/mmr.2016.5919. Epub 2016 Nov 1.