Ryan A Sheikh, Muhammad Afzal, Fahad A Al-Abbasi, Hussam A Bukhari, Naif A R Almalki, May M Alqurashi, Faisal Imam, Nadeem Sayyed, Imran Kazmi
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The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1β (IL-1β), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets.</p><p><strong>Results: </strong>Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1β, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol.</p><p><strong>Conclusion: </strong>The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway.\",\"authors\":\"Ryan A Sheikh, Muhammad Afzal, Fahad A Al-Abbasi, Hussam A Bukhari, Naif A R Almalki, May M Alqurashi, Faisal Imam, Nadeem Sayyed, Imran Kazmi\",\"doi\":\"10.2174/0109298673307759240614114201\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally.</p><p><strong>Objective: </strong>The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. 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引用次数: 0
摘要
背景：甲基苯丙胺（MA）是一种公认的精神兴奋剂，可导致神经毒性和神经变性，而神经变性与认知能力下降有关，这一点已在实验中得到证实：本研究旨在探讨乌洛托品（Eu）对受甲基苯丙胺（MA）诱导的认知障碍和海马体改变影响的啮齿类动物的神经保护特性。这是通过抑制脂质过氧化和促炎标记物来实现的：方法：将大鼠暴露于 MA 引起的认知障碍中。方法：将大鼠暴露于 MA 产生的认知障碍中，利用莫里斯水迷宫（MWM）评估行为参数。对丙二醛 (MDA)、过氧化氢酶 (CAT)、白细胞介素-1β (IL-1β)、还原型谷胱甘肽 (GSH)、肿瘤坏死因子-α (TNF-α)、超氧化物歧化酶 (SOD) 以及神经递质（去甲肾上腺素 [NE]、多巴胺 [DA]、谷氨酰胺 [GSH]）的表达进行了测试、多巴胺[DA]、谷氨酸和γ-氨基丁酸[GABA]）以及 cAMP 反应元件结合蛋白（CREB）、IL-6、脑源性神经营养因子（BDNF）和 Caspase 3 蛋白的表达。利用对接方法进行了调查，以确定 Eu 是否与相关分子靶点相互作用：结果：与 MA 诱导的大鼠相比，Eu 处理的大鼠转运潜伏期显著下降，SOD、GSH、CAT 和 MDA 的含量发生了显著变化，IL-6、IL-1β、CREB、TNF-α、BDNF 和 Caspase 3 蛋白表达水平发生了变化，神经递质（NE、DA、谷氨酸和 GABA）的水平也发生了显著变化。Eu 与 BDNF 有良好的亲和力，对接分数为 -9.486 kcal/mol：实验发现，与用 MA 治疗的对照组大鼠相比，给大鼠注射 Eu 可通过改变抗氧化酶、减少细胞因子和改变神经递质水平来提高认知能力。
Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway.
Background: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally.
Objective: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers.
Methods: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1β (IL-1β), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets.
Results: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1β, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol.
Conclusion: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.
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Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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