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Mitigation of oxidative stress with dihydroactinidiolide, a natural product against scopolamine-induced amnesia in Swiss albino mice
NeuroToxicology ( IF 3.4 ) Pub Date : 2021-08-08 , DOI: 10.1016/j.neuro.2021.08.003
Mamali Das 1 , Devasahayam Jaya Balan 1 , Pandima Devi Kasi 1
Affiliation  

The present work describes the neuroprotective efficacy of DHAc under escalated oxidative stress condition in scopolamine-induced amnesic mice. During the toxicity test of DHAc in mice, the acute dose (LD50) is found to be 3.468 mg/kg bw and the sub-acute dose is 0.68 mg/kg bw. Improved cognitive and learning abilities are observed in Morris water maze and Y-maze test in 10 days DHAc (0.68 mg/kg bw) treated scopolamine-induced male Swiss albino mice. In the molecular level these changes are monitored as reduced oxidative load followed by significantly lower lipid peroxidation and protein carbonylation, increased superoxide dismutase, catalase, acetylcholinesterase, caspase-3 activity and glutathione content followed by higher expression of anti apoptotic protein bcl-2 in mice brain as compared to scopolamine (1 mg/kg bw) treated mice. Meanwhile real time PCR shows higher expression of brain derived neurotrophic factor (BDNF) and synaptophysin in DHAc pretreated scopolamine treated mice brain. HPLC analysis suggested its possible blood brain barrier crossing ability. Overall DHAc reversed behavioral anomalies in the scopolamine treated mice via oxidative stress quenching, enhancing antioxidative enzyme activity, enhancing BDNF and synaptophysin mRNA levels and reducing expression of apoptotic protein Bax.



中文翻译:

用二氢actinidiolide缓解氧化应激,这是一种天然产品,可对抗瑞士白化小鼠东莨菪碱诱导的健忘症

目前的工作描述了 DHAc 在东莨菪碱诱导的健忘小鼠中在升级的氧化应激条件下的神经保护功效。在小鼠DHAc毒性试验中,急性剂量(LD 50) 被发现为 3.468 毫克/公斤体重,亚急性剂量为 0.68 毫克/公斤体重。在 DHAc (0.68 mg/kg bw) 处理东莨菪碱诱导的雄性瑞士白化病小鼠 10 天后,在 Morris 水迷宫和 Y 迷宫测试中观察到认知和学习能力得到改善。在分子水平上,这些变化被监测为氧化负荷降低,随后脂质过氧化和蛋白质羰基化显着降低,超氧化物歧化酶、过氧化氢酶、乙酰胆碱酯酶、caspase-3 活性和谷胱甘肽含量增加,随后小鼠抗凋亡蛋白 bcl-2 表达升高与东莨菪碱(1 mg/kg bw)处理的小鼠相比。同时,实时 PCR 显示在 DHAc 预处理的东莨菪碱处理的小鼠脑中脑源性神经营养因子 (BDNF) 和突触素的表达更高。HPLC分析表明其可能具有穿越血脑屏障的能力。总体而言,DHAc 通过氧化应激猝灭、增强抗氧化酶活性、增强 BDNF 和突触素 mRNA 水平以及降低凋亡蛋白 Bax 的表达来逆转东莨菪碱治疗小鼠的行为异常。

更新日期:2021-08-13
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