Wang Hui, Dai Jian-Ying, He Yu-Zhen, Xia Zhe-Wei, Chen Xiao-Fei, Hong Zhan-Ying, Chai Yi-Feng
Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Naval Medical University, Shanghai, China.
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Front Pharmacol. 2022 Aug 4;13:940555. doi: 10.3389/fphar.2022.940555. eCollection 2022.
(AR) has multiple pharmacological activities to prevent and treat Alzheimer's disease (AD). However, the effect and its molecular mechanism are not elucidated clear. This study aims to evaluate AR's therapeutic effect and mechanism on AD model rats induced by -galactose and AlCl with serum metabolomics. Behavior study, histopathological observations, and biochemical analyses were applied in the AD model assessment. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-QTOF/MS) were combined with multivariate statistical analysis to identify potential biomarkers of AD and evaluate the therapeutic effect of AR on AD from the perspective of metabolomics. A total of 49 biomarkers associated with the AD model were identified by metabolomics, and pathway analysis was performed to obtain the metabolic pathways closely related to the model. With the pre-treatment of AR, 32 metabolites in the serum of AD model rats were significantly affected by AR compared with the AD model group. The regulated metabolites affected by AR were involved in the pathway of arginine biosynthesis, arginine and proline metabolism, ether lipid metabolism, glutathione metabolism, primary bile acid biosynthesis, and steroid biosynthesis. These multi-platform metabolomics analyses were in accord with the results of behavior study, histopathological observations, and biochemical analyses. This study explored the therapeutic mechanism of AR based on multi-platform metabolomics analyses and provided a scientific basis for the application of AR in the prevention and treatment of AD.
黄芪(AR)具有多种预防和治疗阿尔茨海默病(AD)的药理活性。然而,其作用效果及其分子机制尚未完全阐明。本研究旨在通过血清代谢组学评估AR对由半乳糖和氯化铝诱导的AD模型大鼠的治疗效果及机制。行为学研究、组织病理学观察和生化分析被应用于AD模型评估。气相色谱-质谱联用仪(GC-MS)和液相色谱-四极杆飞行时间质谱联用仪(LC-QTOF/MS)与多元统计分析相结合,以鉴定AD的潜在生物标志物,并从代谢组学角度评估AR对AD的治疗效果。通过代谢组学共鉴定出49种与AD模型相关的生物标志物,并进行通路分析以获得与该模型密切相关的代谢途径。经AR预处理后,与AD模型组相比,AD模型大鼠血清中有32种代谢物受到AR的显著影响。受AR调节的代谢物涉及精氨酸生物合成、精氨酸和脯氨酸代谢、醚脂代谢、谷胱甘肽代谢、初级胆汁酸生物合成和类固醇生物合成途径。这些多平台代谢组学分析与行为学研究、组织病理学观察和生化分析结果一致。本研究基于多平台代谢组学分析探索了AR的治疗机制,为AR在AD预防和治疗中的应用提供了科学依据。