Doxorubicin (DOX) is an effective anticancer drug, however, side effects such as cognitive impairment and cardiotoxicity have limited its clinical use. Juglanin (JUG) is a flavonoid with excellent antioxidant, anti-inflammatory, neuroprotective and anticancer properties. This study investigated the protective effects of JUG against DOX-induced cognitive decline, oxidative stress and inflammatory response in rats. The rats were orally administrated with JUG or JUG in combination with DOX. After treatment, the animals were subjected to series of behavioral test including Morris water maze, Y-maze and forced swimming tests. After the study, the rats were sacrificed and the level of acetylcholinesterase (AchE), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), caspase 3 and Nuclear factor kappa B (NF-кB) were assayed in the brain. Histopathological analysis was also performed on the brain of the rats. JUG significantly protected against DOX-induced cognitive impairment and depressive behaviors. In addition, JUG attenuated altered brain histopathological architecture, reduced oxido-inflammatory responses, acetylcholinesterase and caspase 3 activity in the brain of the treated rats. Collectively, the results suggested that JUG offered neuroprotection against DOX induced Chemobrain via ameliorating oxidative stress and inflammation.
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