Department of Neurology, Wuhu Second Peoples Hospital, Wuhu, Anhui, 241001, China.
School of Chinese Medicine, Bozhou University, 236800, Bozhou, China.
Metab Brain Dis. 2022 Apr;37(4):1185-1195. doi: 10.1007/s11011-022-00923-8. Epub 2022 Feb 9.
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.
多柔比星（DOX）是一种有效的抗癌药物，但其引起的认知障碍和心脏毒性等副作用限制了其临床应用。核桃素（JUG）是一种具有良好抗氧化、抗炎、神经保护和抗癌特性的黄酮类化合物。本研究探讨了 JUG 对 DOX 诱导的大鼠认知功能下降、氧化应激和炎症反应的保护作用。大鼠经口给予 JUG 或 JUG 联合 DOX。治疗后，动物进行了一系列行为测试，包括 Morris 水迷宫、Y 迷宫和强迫游泳测试。研究结束后，处死大鼠，检测大脑中乙酰胆碱酯酶（AchE）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、丙二醛（MDA）、白细胞介素 6（IL-6）、白细胞介素 1β（IL-1β）、肿瘤坏死因子α（TNF-α）、半胱氨酸天冬氨酸蛋白酶 3（caspase 3）和核因子 kappa B（NF-кB）的水平，并对大鼠大脑进行组织病理学分析。JUG 显著改善了 DOX 引起的认知障碍和抑郁样行为。此外，JUG 减轻了大脑组织病理结构的改变，降低了氧化应激和炎症反应，降低了治疗大鼠大脑中的乙酰胆碱酯酶和半胱氨酸天冬氨酸蛋白酶 3 活性。综上所述，研究结果表明 JUG 通过改善氧化应激和炎症反应，对 DOX 诱导的化疗性脑损伤提供神经保护作用。
