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超高效液相色谱/质谱技术与高通量代谢组学用于解读芒硝对结直肠癌的预防机制——复杂代谢网络的调控

Ultra-performance liquid chromatography/mass spectrometry technology and high-throughput metabolomics for deciphering the preventive mechanism of mirabilite on colorectal cancer the modulation of complex metabolic networks.

作者信息

Sun Hui, Zhang Ai-Hua, Zhang Hong-Lian, Zhou Xiao-Hang, Wang Xiang-Qian, Liu Liang, Wang Xi-Jun

机构信息

National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine Heping Road 24 Harbin China

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology Avenida Wai Long, Taipa Macau China.

出版信息

RSC Adv. 2019 Oct 31;9(61):35356-35363. doi: 10.1039/c9ra07687e.

Abstract

Colorectal cancer (CRC) is a highly virulent and malignant disease and always accompanied by metabolic disorders. Currently, there are no effective therapeutic drugs for the treatment of CRC. High-throughput metabolomics approaches have been used to unveil the metabolic pathways related to several diseases. In this study, ultra-performance liquid chromatography/mass spectrometry-based high-throughput metabolomics was used for deciphering the potential preventive mechanism of mirabilite on CRC the modulation of the associated metabolic disorders; a total of 28 differential biomarkers, including indole acetaldehyde, 5-hydroxyindoleacetic acid, hypoxanthine, retinal, retinal ester, linoleic acid, stearic acid, 6-deoxocastasterone, 2-hydroxybutyric acid and LysoPC, were identified in the APC mice. These differential biomarkers are involved in the tryptophan metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Note that these biomarkers and their disturbed metabolic pathways were also regulated by mirabilite. It has been found that the prevention of CRC by mirabilite is mainly associated with tryptophan metabolism; this study shows that high-throughput metabolomics can reveal the perturbed metabolic disorders targeted in the action mechanism of drug treatment.

摘要

结直肠癌(CRC)是一种高侵袭性和恶性疾病,常伴有代谢紊乱。目前,尚无有效的治疗CRC的药物。高通量代谢组学方法已被用于揭示与多种疾病相关的代谢途径。在本研究中,基于超高效液相色谱/质谱的高通量代谢组学被用于解读芒硝对CRC的潜在预防机制以及相关代谢紊乱的调节作用;在Apc小鼠中总共鉴定出28种差异生物标志物,包括吲哚乙醛、5-羟吲哚乙酸、次黄嘌呤、视黄醛、视黄醛酯、亚油酸、硬脂酸、6-脱氧卡甾酮、2-羟基丁酸和溶血磷脂酰胆碱。这些差异生物标志物参与色氨酸代谢、甘油磷脂代谢和不饱和脂肪酸的生物合成。值得注意的是,这些生物标志物及其紊乱的代谢途径也受到芒硝的调节。已发现芒硝对CRC的预防主要与色氨酸代谢有关;本研究表明,高通量代谢组学可以揭示药物治疗作用机制中所针对的代谢紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9657/9074663/5a2edb6d7e0c/c9ra07687e-f1.jpg

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