Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats

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-kappa B, tumor necrosis factor (TNF)-alpha, IL-1 beta, 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.