Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1
Yang, Xiao-Nan1,5; Wang, Yi-Kun1,2; Zhu, Xu1,2; Xiao, Xue-Rong1; Dai, Man-Yun1,2; Zhang, Ting1,2; Qu, Yan1; Yang, Xiu-Wei3; Qin, Hong-Bo1; Gonzalez, Frank J.4; Li, Fei1
Corresponding AuthorLi, Fei(
AbstractElemicin is a constituent of natural aromatic phenyl-propanoids present in many herbs and spices. However, its potential to cause toxicity remains unclear. To examine the potential toxicity and associated mechanism, elemicin was administered to mice for 3 weeks and serum metabolites were examined. Enlarged livers were observed in elemicin-treated mice, which were accompanied by lower ratios of unsaturated- and saturated-lysophosphatidylcholines in plasma, and inhibition of stearoyl-CoA desaturase 1 (Scd1) mRNA expression in liver. Administration of the unsaturated fatty acid oleic acid reduced the toxicity of 1'-hydroxylelemicin, the primary oxidative metabolite of elemicin, while treatment with the SCD1 inhibitor A939572 potentiated its toxicity. Furthermore, the in vitro use of recombinant human CYPs and chemical inhibition of CYPs in human liver microsomes revealed that 0 CYP1A1 and CYP1A2 were the primary CYPs responsible for elemicin bioactivation. Notably, the CYP1A2 inhibitor alpha-naphthoflavone could attenuate the susceptibility of mice to elemicin-induced hepatomegaly. This study revealed that metabolic activation of elemicin leads to SCD1 inhibition in liver, suggesting that upregulation of SCD1 may serve as potential intervention strategy for elemicin-induced toxicity.
Indexed BySCI ; SCI
WOS IDWOS:000492118000007
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Document Type期刊论文
Corresponding AuthorLi, Fei
Affiliation1.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.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
4.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
5.Guangxi Bot Garden Med Plant, Guangxi Key Lab Med Resources Protect & Genet Imp, Nanning 530023, Peoples R China
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GB/T 7714
Yang, Xiao-Nan,Wang, Yi-Kun,Zhu, Xu,et al. Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2019,32(10):1965-1976.
APA Yang, Xiao-Nan.,Wang, Yi-Kun.,Zhu, Xu.,Xiao, Xue-Rong.,Dai, Man-Yun.,...&Li, Fei.(2019).Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1.CHEMICAL RESEARCH IN TOXICOLOGY,32(10),1965-1976.
MLA Yang, Xiao-Nan,et al."Metabolic Activation of Elemicin Leads to the Inhibition of Stearoyl-CoA Desaturase 1".CHEMICAL RESEARCH IN TOXICOLOGY 32.10(2019):1965-1976.
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