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基于液质联用代谢组学方法研究山楂提取物不同极性部位对血瘀模型大鼠的作用

Therapeutic effects of different polar fractions of hawthorn extract on blood stasis model rats revealed by liquid chromatography-mass spectrometry metabolomics.

机构信息

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, P. R. China.

Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administrationof TCM, Guangdong Pharmaceutical University, Guangzhou, P. R. China.

出版信息

J Sep Sci. 2021 Nov;44(21):4005-4016. doi: 10.1002/jssc.202100569. Epub 2021 Sep 14.

Abstract

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography-mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n-butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d-glutamine and d-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways.

摘要

山楂是一种常用的中药,被认为对心血管疾病有治疗作用。然而,山楂提取物在心血管疾病治疗中的有效部位以及可能的治疗机制仍不清楚。本研究旨在探讨山楂提取物的四种不同极性部位对血瘀模型大鼠的作用,并采用液相色谱-质谱代谢组学方法探讨可能的代谢机制。血液流变学和纤维蛋白原的评价表明,山楂提取物的正丁醇和乙酸乙酯部位对血瘀模型大鼠有显著的治疗作用。此外,代谢组学分析表明,山楂提取物的正丁醇和乙酸乙酯部位可以逆转血瘀模型大鼠血浆和尿液中失衡的生物标志物。此外,代谢途径分析表明,血浆生物标志物与包括 D-谷氨酰胺和 D-谷氨酸代谢、苯丙氨酸、酪氨酸和色氨酸生物合成、丙氨酸、天冬氨酸和谷氨酸代谢、鞘脂代谢和精氨酸生物合成在内的几个重要途径有关。同时,尿液生物标志物与包括苯丙氨酸代谢、酪氨酸代谢和赖氨酸降解在内的一些重要途径有关。本研究表明,山楂提取物的正丁醇和乙酸乙酯部位对血瘀模型大鼠有显著的治疗作用,其作用机制涉及多个代谢途径。

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