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苦荞麦皮通过调节 Gsk-3β/β-catenin 通路预防手术去卵巢大鼠模型的神经行为损伤。

Buckwheat tartary regulates the Gsk-3β/β-catenin pathway to prevent neurobehavioral impairments in a rat model of surgical menopause.

机构信息

Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

Metab Brain Dis. 2023 Aug;38(6):1859-1875. doi: 10.1007/s11011-023-01213-7. Epub 2023 May 3.

DOI:10.1007/s11011-023-01213-7
PMID:37133802
Abstract

Menopause is a natural aging process characterized by decreased levels of sex hormones in females. Deprivation of estrogen following menopause results in alterations of dendritic arborization of the neuron that leads to neurobehavioral complications. Hormone replacement therapy is in practice to manage postmenopausal conditions but is associated with a lot of adverse effects. In the present study, the efficacy of buckwheat tartary (Fagopyrum tataricum) whole seed extract was investigated against the neurobehavioral complication in middle-aged ovariectomized rats, which mimic the clinical postmenopausal condition. Hydroalcoholic extraction (80% ethanol) was done, and quantification of major marker compounds in the extract was performed using HPLC. Oral treatment of the extract following the critical window period rescued the reconsolidation process of spatial and recognition memory, as well as depression-like behavior. Gene expression analysis disclosed elevated oxidative stress and neuroinflammation that largely disturb the integrity of the blood-brain barrier in ovariectomized rats. Gfap and Pparγ expression also showed reactive astrogliosis in the rats subjected to ovariectomy. The extract treatment reverted the elevated oxidative stress, neuroinflammation and expression of the studied genes. Furthermore, protein expression analysis revealed that Gsk-3β was activated differentially in the brain, as suggested by β-catenin protein expression, which was normalized following the treatment with extract and rescued the altered neurobehavioral process. The results of the current study concluded that Fagopyrum tataricum seed extract is better option to overcome the neurobehavioral complications associated with the menopause.

摘要

绝经是女性性激素水平下降的自然衰老过程。绝经后雌激素的缺乏导致神经元树突分支的改变,从而导致神经行为并发症。激素替代疗法是用于治疗绝经后症状的,但它也有很多不良反应。在本研究中,研究了苦荞(Fagopyrum tataricum)全籽提取物对中年去卵巢大鼠神经行为并发症的疗效,这种大鼠模拟了临床绝经后状况。进行了水醇提取(80%乙醇),并使用 HPLC 对提取物中的主要标记化合物进行了定量。在关键窗口期后进行提取物的口服治疗,挽救了空间和识别记忆的再巩固过程以及抑郁样行为。基因表达分析显示,氧化应激和神经炎症升高,这在很大程度上扰乱了去卵巢大鼠血脑屏障的完整性。GFAP 和 PPARγ 的表达也显示出卵巢切除大鼠的反应性星形胶质细胞增生。提取物处理使氧化应激、神经炎症和所研究基因的表达升高得到逆转。此外,蛋白质表达分析显示,Gsk-3β在大脑中的活性不同,β-连环蛋白的蛋白表达表明了这一点,而在提取物治疗后,β-连环蛋白的蛋白表达得到了正常化,并挽救了改变的神经行为过程。本研究的结果表明,苦荞籽提取物是克服与绝经相关的神经行为并发症的更好选择。

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