Comparative Metabolomic Profiling of the Metabolic Differences of Delta 9-Tetrahydrocannabinol and Cannabidiol

doi:10.3390/molecules27217573

KIB OpenIR

	Comparative Metabolomic Profiling of the Metabolic Differences of Delta 9-Tetrahydrocannabinol and Cannabidiol
	Rao, Qianru; Zhang, Ting; Dai, Manyun; Li, Bin; Pu, Qianlun; Zhao, Min; Cheng, Yan; Yan, Dongmei; Zhao, Qi; Wu, Zhanxuan E.; Li, Fei
	2022
发表期刊	MOLECULES
卷号	27 期号:21 页码:7573
摘要	More than one hundred cannabinoids have been found in cannabis. Delta 9-Tetrahydrocannabinol (THC) is the recognized addictive constituent in cannabis; however, the mechanisms underlying THC-induced toxicity remain elusive. To better understand cannabis-induced toxicity, the present study compared the metabolic pathways of THC and its isomer cannabidiol (CBD) in human and mouse liver microsomes using the metabolomic approach. Thirty-two metabolites of THC were identified, including nine undescribed metabolites. Of note, two glutathione (GSH) and two cysteine (Cys) adducts were found in THC's metabolism. Molecular docking revealed that THC conjugates have a higher affinity with GSH and Cys than with the parent compound, THC. Human recombinant cytochrome P450 enzymes, and their corresponding chemical inhibitors, demonstrated that CYP3A4 and CYP1B1 were the primary enzymes responsible for the formation of THC-GSH and THC-Cys, thus enabling conjugation to occur. Collectively, this study systematically compared the metabolism of THC with the metabolism of CBD using the metabolomic approach, which thus highlights the critical role of metabolomics in identifying novel drug metabolites. Moreover, this study also facilitates mechanistic speculation in order to expand the knowledge of drug metabolism and safety.
关键词	cannabis Delta 9-tetrahydrocannabinol cannabidiol metabolomics CANNABINOIDS
DOI	10.3390/molecules27217573
收录类别	SCI
WOS记录号	WOS:000884041700001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74702
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Rao, Qianru,Zhang, Ting,Dai, Manyun,et al. Comparative Metabolomic Profiling of the Metabolic Differences of Delta 9-Tetrahydrocannabinol and Cannabidiol[J]. MOLECULES,2022,27(21):7573.
APA	Rao, Qianru.,Zhang, Ting.,Dai, Manyun.,Li, Bin.,Pu, Qianlun.,...&Li, Fei.(2022).Comparative Metabolomic Profiling of the Metabolic Differences of Delta 9-Tetrahydrocannabinol and Cannabidiol.MOLECULES,27(21),7573.
MLA	Rao, Qianru,et al."Comparative Metabolomic Profiling of the Metabolic Differences of Delta 9-Tetrahydrocannabinol and Cannabidiol".MOLECULES 27.21(2022):7573.

条目包含的文件		下载所有文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
ARTN 7573.pdf（2786KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	浏览下载