Role of Metabolic Activation in Elemicin-Induced Cellular Toxicity
Wang, Yi-Kun1,2; Yang, Xiao-Nan1,3; Zhu, Xu1,2; Xiao, Xue-Rong1; Yang, Xiu-Wei4; Qin, Hong-Bo1; Gonzalez, Frank J.5; Li, Fei1
Corresponding AuthorQin, Hong-Bo( ; Li, Fei(
AbstractElemicin, an alkenylbenzene constituent of natural oils of several plant species, is widely distributed in food, dietary supplements, and medicinal plants. 1'-Hydroxylation is known to cause metabolic activation of alkenylbenzenes leading to their potential toxicity. The aim of this study was to explore the relationship between elemicin metabolism and its toxicity through comparing the metabolic maps between elemicin and 1'-hydroxyelemicin. Elemicin was transformed into a reactive metabolite of 1'-hydroxyelemicin, which was subsequently conjugated with cysteine (Cys) and N-acetylcysteine (NAC). Administration of NAC could significantly ameliorate the elemicin- and 1'-hydroxyelemicin-induced cytotoxicity of HepG2 cells, while depletion of Cys with diethyl maleate (DEM) increased cytotoxicity. Recombinant human CYP screening and CYP inhibition experiments revealed that multiple CYPs, notably CYP1A1, CYP1A2, and CYP3A4, were responsible for the metabolic activation of elemicin. This study revealed that metabolic activation plays a critical role in elemicin cytotoxicity.
Keywordelemicin l'-hydroxyelemicin metabolic activation cytotoxicity
Indexed BySCI
WOS IDWOS:000477788100020
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Document Type期刊论文
Corresponding AuthorQin, Hong-Bo; Li, Fei
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, 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, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
5.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
Recommended Citation
GB/T 7714
Wang, Yi-Kun,Yang, Xiao-Nan,Zhu, Xu,et al. Role of Metabolic Activation in Elemicin-Induced Cellular Toxicity[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2019,67(29):8243-8252.
APA Wang, Yi-Kun.,Yang, Xiao-Nan.,Zhu, Xu.,Xiao, Xue-Rong.,Yang, Xiu-Wei.,...&Li, Fei.(2019).Role of Metabolic Activation in Elemicin-Induced Cellular Toxicity.JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,67(29),8243-8252.
MLA Wang, Yi-Kun,et al."Role of Metabolic Activation in Elemicin-Induced Cellular Toxicity".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 67.29(2019):8243-8252.
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