机构：[1]Laboratory of Metabolomics and Drug-Induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院[2]Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, China[3]States Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China[4]Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院[5]Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Department of Gastroenterology & Hepatology,Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院
Delta(9)-tetrahydrocannabinolic acid (THCA) and Delta(9)-tetrahydrocannabivarin (THCV) are phytocannabinoids with a similar structure derived from Cannabis sativa and possess a variety of biological activities. However, the relationship between the metabolic characterization and bioactivity of THCA and THCV remains elusive.To explore the relationship between the metabolism of THCA and THCV and their underlying mechanism of activity, human/mouse liver microsomes and mouse primary hepatocytes were used to compare the metabolic maps between THCA and THCV through comparative metabolomics. A total of 29 metabolites were identified containing 7 previously undescribed THCA metabolites and 10 previously undescribed THCV metabolites. Of these metabolites, THCA was transformed into an active metabolite of THC in these three systems, while THCV was transformed into THC and CBD.Bioactivity assays indicated that all of these phytocannabinoids exhibited anti-inflammatory activity, but the effects of THCA and THCV were sightly difference in macrophages RAW264.7. Prediction of ADMET lab demonstrated that THCV and its metabolites were endowed with the advantage of BBB (blood-brain barrier) penetration compare to THCA.In conclusion, this study highlighted that metabolism plays a critical role in the biological activity of phytocannabinoids.
基金：
This work was supported by the National Key Research and Development Program of China (2021YFF0702003), 1.3.5 Project for Disciplines of Excellence from West China Hospital, “the Fundamental Research Funds for the Central Universities (2022SCU12054)”, “Post-Doctor Research Project, West China Hospital, Sichuan University (2021HXBH041)”.We thank XinChuan Advanced Mass Spectrometry Center of West China Hospital for LC-MS tests
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|4 区医学
小类|4 区药学4 区毒理学
最新[2023]版：
大类|4 区医学
小类|4 区药学4 区毒理学
第一作者：
第一作者机构：[1]Laboratory of Metabolomics and Drug-Induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China[2]Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, China
共同第一作者：
通讯作者：
通讯机构：[1]Laboratory of Metabolomics and Drug-Induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China[2]Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, China[5]Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Department of Gastroenterology & Hepatology,Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China[*1]rontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041,China[*2]Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
推荐引用方式(GB/T 7714)：
Rao Qianru,Zhang Ting,Pu Qian-Lun,et al.Comparative metabolism of THCA and THCV using UHPLC-Q-Exactive Orbitrap-MS[J].Xenobiotica; the fate of foreign compounds in biological systems.2023,1-42.doi:10.1080/00498254.2023.2194981.
APA：
Rao Qianru,Zhang Ting,Pu Qian-Lun,Li Bin,Zhao Qi...&Li Fei.(2023).Comparative metabolism of THCA and THCV using UHPLC-Q-Exactive Orbitrap-MS.Xenobiotica; the fate of foreign compounds in biological systems,,
MLA：
Rao Qianru,et al."Comparative metabolism of THCA and THCV using UHPLC-Q-Exactive Orbitrap-MS".Xenobiotica; the fate of foreign compounds in biological systems .(2023):1-42
