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酢浆草甲醇提取物在实验大鼠中的潜在抗阿尔茨海默病活性:载脂蛋白E4/低密度脂蛋白受体相关蛋白1、Toll样受体4/核因子κB/核苷酸结合寡聚化结构域样受体蛋白3、Wnt 3/β-连环蛋白/糖原合成酶激酶-3β、自噬和凋亡信号的作用

The potential anti-Alzheimer's activity of Oxalis corniculata Linn. Methanolic extract in experimental rats: Role of APOE4/LRP1, TLR4/NF-κβ/NLRP3, Wnt 3/β-catenin/GSK-3β, autophagy and apoptotic cues.

作者信息

Abu-Elfotuh Karema, Hamdan Ahmed M E, Mohamed Shaza A, Bakr Riham O, Ahmed Amal H, Atwa Ahmed M, Hamdan Amira M, Alanzai Ahad Ghanem, Alnahhas Raghad Khalid, Gowifel Ayah M H, Salem Maha A

机构信息

Clinical Pharmacy Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt; Al-Ayen Iraqi University, Thi-Qar, 64001, Iraq.

Pharmacy Practice Department, Faculty of Pharmacy, University of Tabuk, Tabuk 74191, Saudi Arabia.

出版信息

J Ethnopharmacol. 2024 Apr 24;324:117731. doi: 10.1016/j.jep.2024.117731. Epub 2024 Jan 11.


DOI:10.1016/j.jep.2024.117731
PMID:38218505
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Oxalis corniculata (O. corniculata) is a member of Oxalidaceae family, widely distributed in Asia, Europe, America, and Africa, used extensively as food and its traditional folkloric uses include management of epilepsy, gastric disorders, and neurodegenerative diseases, together with its use in enhancing health. Numerous pharmacological benefits of O. corniculata are linked to its anti-inflammatory and antioxidant abilities. One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD) in which neuroinflammation and oxidative stress are its main pathogenic processes. AIM OF THE STUDY: Our research aimed to study the neuroprotective effect of the methanolic extract of Oxalis corniculata Linn. (O. corniculata ME), compared to selenium (Se) against AlCl-induced AD. MATERIALS AND METHODS: Forty male albino rats were allocated into four groups (Gps). Gp I a control group, the rest of the animals received AlCl (Gp II-Gp IV). Rats in Gp III and IV were treated with Se and O. corniculata ME, respectively. RESULTS: The chemical profile of O. corniculata ME was studied using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, allowing the tentative identification of sixty-six compounds, including organic acids, phenolics and others, cinnamic acid and its derivatives, fatty acids, and flavonoids. AlCl showed deterioration in short-term memory and brain histological pictures. Our findings showed that O. corniculata ME and selenium helped to combat oxidative stress produced by accumulation of AlCl in the brain and in prophylaxis against AD. Thus, Selenium (Se) and O. corniculata ME restored antioxidant defense, via enhancing Nrf2/HO-1 hub, hampered neuroinflammation, via TLR4/NF-κβ/NLRP3, along with dampening apoptosis, Aβ generation, tau hyperphosphorylation, BACE1, ApoE4 and LRP1 levels. Treatments also promoted autophagy and modulated Wnt 3/β-catenin/GSK3β cue. CONCLUSIONS: It was noted that O. corniculata ME showed a notable ameliorative effect compared to Se on Nrf2/HO-1, TLR4/NF-κβ/NLRP3, APOE4/LRP1, Wnt 3/β-catenin/GSK-3β and PERK axes.

摘要

民族药理学相关性:酢浆草是酢浆草科的一员,广泛分布于亚洲、欧洲、美洲和非洲,被广泛用作食物,其传统民间用途包括治疗癫痫、胃部疾病和神经退行性疾病,以及用于增进健康。酢浆草的许多药理益处与其抗炎和抗氧化能力有关。最常见的神经退行性疾病之一是阿尔茨海默病(AD),其中神经炎症和氧化应激是其主要致病过程。 研究目的:我们的研究旨在研究酢浆草甲醇提取物(O. corniculata ME)与硒(Se)相比对氯化铝诱导的AD的神经保护作用。 材料与方法:将40只雄性白化大鼠分为四组(Gps)。第一组为对照组,其余动物接受氯化铝处理(第二组至第四组)。第三组和第四组的大鼠分别用硒和酢浆草甲醇提取物进行处理。 结果:使用超高效液相色谱 - 电喷雾电离 - 四极杆飞行时间质谱法研究了酢浆草甲醇提取物的化学组成,初步鉴定出66种化合物,包括有机酸、酚类及其他、肉桂酸及其衍生物、脂肪酸和黄酮类化合物。氯化铝显示出短期记忆和脑组织结构图的恶化。我们的研究结果表明,酢浆草甲醇提取物和硒有助于对抗大脑中氯化铝积累产生的氧化应激,并预防AD。因此,硒(Se)和酢浆草甲醇提取物通过增强Nrf2/HO-1轴心恢复抗氧化防御,通过TLR4/NF-κβ/NLRP3抑制神经炎症,同时抑制细胞凋亡、Aβ生成、tau过度磷酸化、BACE1、ApoE4和LRP1水平。治疗还促进自噬并调节Wnt 3/β-连环蛋白/GSK3β信号通路。 结论:值得注意的是,与硒相比,酢浆草甲醇提取物在Nrf2/HO-1、TLR4/NF-κβ/NLRP3、APOE4/LRP1、Wnt 3/β-连环蛋白/GSK-3β和PERK轴线上显示出显著的改善作用。

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