Metabolic Activation of Myristicin and Its Role in Cellular Toxicity

doi:10.1021/acs.jafc.9b00893

	Metabolic Activation of Myristicin and Its Role in Cellular Toxicity
	Zhu, Xu 1,2; Wang, Yi-Kun 1,2; Yang, Xiao-Nan 1,3; Xiao, Xue-Rong 1; Zhang, Ting 1,2; Yang, Xiu-Wei 4; Qin, Hong-Bo1 ; Li, Fei 1,5
通讯作者	Qin, Hong-Bo(qinhongbo@mail.kib.ac.cn) ; Li, Fei(lifeib@mail.kib.ac.cn)
	2019-04-17
发表期刊	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
ISSN	0021-8561
卷号	67 期号:15 页码:4328-4336
摘要	Myristicin is widely distributed in spices and medicinal plants. The aim of this study was to explore the role of metabolic activation of myristicin in its potential toxicity through a metabolomic approach. The myristicin-N-acetylcysteine adduct was identified by comparing the metabolic maps of myristicin and 1'-hydroxymyristicin. The supplement of N-acetylcysteine could protect against the cytotoxicity of myristicin and 1'-hydroxymyristicin in primary mouse hepatocytes. When the depletion of intracellular N-acetylcysteine was pretreated with diethyl maleate in hepatocytes, the cytotoxicity induced by myristicin and 1'-hydroxymyristicin was deteriorated. It suggested that the N-acetylcysteine adduct resulting from myristicin bioactivation was closely associated with myristicin toxicity. Screening of human recombinant cytochrome P450s (CYPs) and treatment with CYP inhibitors revealed that CYP1A1 was mainly involved in the formation of 1'-hydroxymyristicin. Collectively, this study provided a global view of myristicin metabolism and identified the N-acetylcysteine adduct resulting from myristicin bioactivation, which could be used for understanding the mechanism of myristicin toxicity.
关键词	myristicin 1 '-hydroxymyristicin metabolic activation metabolomics
DOI	10.1021/acs.jafc.9b00893
收录类别	SCI
语种	英语
WOS记录号	WOS:000465189400022
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/66349
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Qin, Hong-Bo; Li, Fei
作者单位	1.Chinese Acad Sci, Kunming Inst Bot, States Key Lab Phytochem & Plant Resources West C, Kunming 650201, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Guangxi Bot Garden Med Plant, Guangxi Key Lab Med Resources Protect & Genet Imp, Nanning 530023, Guangxi, Peoples R China 4.Peking Univ, Sch Pharmaceut Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China 5.Jiangxi Univ Tradit Chinese Med, Nanchang 330004, Jiangxi, Peoples R China
推荐引用方式 GB/T 7714	Zhu, Xu,Wang, Yi-Kun,Yang, Xiao-Nan,et al. Metabolic Activation of Myristicin and Its Role in Cellular Toxicity[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2019,67(15):4328-4336.
APA	Zhu, Xu.,Wang, Yi-Kun.,Yang, Xiao-Nan.,Xiao, Xue-Rong.,Zhang, Ting.,...&Li, Fei.(2019).Metabolic Activation of Myristicin and Its Role in Cellular Toxicity.JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,67(15),4328-4336.
MLA	Zhu, Xu,et al."Metabolic Activation of Myristicin and Its Role in Cellular Toxicity".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 67.15(2019):4328-4336.

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