Neuropharmacology division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.
Neuropharmacology division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.
Neurosci Lett. 2023 Mar 16;799:137090. doi: 10.1016/j.neulet.2023.137090. Epub 2023 Jan 20.
Alzheimer's disease (AD) is a most common and prevalent age related insidious neurological condition characterised by formation of Aβ plaques and NFT in the hippocampus. Major symptoms of AD include memory and cognitive loss caused by neuroinflammation, Aβ plaques, and NFT accumulation in the brain. Intracerebroventricular administration of STZ up-regulates the level of Aβ plaques, and NFT by activating NF-kB pathway. All animals were trained for behaviour analysis before infusion of ICV-STZ bilaterally, at a dose of 3 mg/kg; icv. The stereotaxic surgery was performed in target region with coordinates -2 mm [AP], 1.6 mm [MR], and1.5 mm [DV]. On day 1 and day 3 after surgery HS (hamilton syringe) was used to infuse STZ at the target region of brain. Morris Water Maze (MWM), and Elevated Plus Maze (EPM) tests were performed to check spatial and learning memory in all groups. ICV-STZ infusion produced memory impairment by increasing the activity of AchE, oxidative markers (LPO, GSH, and nitrite), neurotransmitters levels (AchE, GABA, and glutamate), and release of neuroinflammatory markers (NF-kB, IL-6, and IL-1β). The treatment with Honokiol (Bioactive polyphenolic compound) significantly ameliorated the behavioural changes at a dose of 5, and 10 mg/kg; i.p on day 7, 14, and 21. After behavioural analysis rats were sacrificed on day 22, and the hippocampus tissue was collected to investigate the biochemical, neuroinflammatory, neurotransmitters, histopathological, and immunohistopathological changes. Here, we have found Honokiol significantly down regulates the Aβ plaques via NF-kB inhibition and also reduced neuroinflammation in the brain of rats. Further inhibits the NF-kB expression confirmed for immunohistochemistry analysis. It was observed that Honokiol (5, and 10 mg/kg; i.p) dose-dependently ameliorated AchE level restored neurotransmitters concentrations in hippocampal region, and prevented neuronal loss confirmed from histopathology studies. We concluded that Honokiol drastically produced protective effect in AD model via antioxidant, reducing inflammation, AchE level, restoration of neurofibrillary tangles and preventing NF-kB as well as histopathological changes.
阿尔茨海默病（AD）是一种最常见和最普遍的与年龄相关的隐匿性神经疾病，其特征是在海马体中形成 Aβ 斑块和 NFT。AD 的主要症状包括神经炎症、Aβ 斑块和 NFT 在大脑中的积累导致的记忆和认知丧失。侧脑室给予 STZ 可通过激活 NF-κB 通路上调 Aβ 斑块和 NFT 的水平。所有动物在双侧侧脑室注射 STZ 前都接受了行为分析训练，剂量为 3mg/kg；icv。立体定向手术在靶点进行，坐标为-2mm[AP]、1.6mm[MR]和 1.5mm[DV]。在手术后第 1 天和第 3 天，使用 Hamilton 注射器在大脑的目标区域注入 STZ。进行 Morris 水迷宫（MWM）和高架十字迷宫（EPM）测试，以检查所有组的空间和学习记忆。侧脑室注射 STZ 通过增加 AchE、氧化标志物（LPO、GSH 和亚硝酸盐）、神经递质水平（AchE、GABA 和谷氨酸）和神经炎症标志物（NF-κB、IL-6 和 IL-1β）的活性导致记忆损伤。用 honokiol（生物活性多酚化合物）治疗可显著改善 5mg/kg 和 10mg/kg；ip 剂量在第 7、14 和 21 天的行为变化。在行为分析后，大鼠于第 22 天被处死，收集海马组织以研究生化、神经炎症、神经递质、组织病理学和免疫组织化学变化。在这里，我们发现 honokiol 通过抑制 NF-κB 显著下调 Aβ 斑块，同时减少大鼠大脑中的神经炎症。通过免疫组织化学分析进一步证实了对 NF-κB 表达的抑制。观察到 honokiol（5mg/kg 和 10mg/kg；ip）剂量依赖性地改善了 AchE 水平，恢复了海马区神经递质浓度，并从组织病理学研究中证实了神经元丢失的预防。我们得出结论， honokiol 通过抗氧化、减少炎症、AchE 水平、神经纤维缠结的恢复以及 NF-κB 和组织病理学变化，在 AD 模型中产生了显著的保护作用。
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