机构：[1]National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.[2]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China.[3]State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou 510006, China.
3,4,5,4'-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in ApcMin/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireXTM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model ApcMin/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the ApcMin/+ mice's intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.
基金：
This research was funded by the Key Projects of the National Natural Science Foundation
of China, grant number 81830110, and the Heilongjiang Province General Undergraduate Colleges
and Universities Young Innovative Talents Training Plan (UNPYSCT-2020226).
第一作者机构：[1]National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
通讯作者：
通讯机构：[1]National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.[2]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China.[3]State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou 510006, China.
推荐引用方式(GB/T 7714)：
Li Jing,Li Xinghua,Zhou Xiaohang,et al.In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS[J].MOLECULES.2023,28(9):doi:10.3390/molecules28093828.
APA：
Li Jing,Li Xinghua,Zhou Xiaohang,Yang Le,Sun Hui...&Wang Xijun.(2023).In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS.MOLECULES,28,(9)
MLA：
Li Jing,et al."In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS".MOLECULES 28..9(2023)
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