DICP OpenIR
Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: Thiol conjugation as a potential metabolic pathway
Zhou, Bailun1; Ye, Ji2; Yang, Niao2; Chen, Liping2; Zhuo, Zhiguo2; Mao, Ling2; Liu, Qun2; Lan, Gongcai1; Ning, Jing4; Ge, Guangbo4; Yang, Ling4; Shen, Yunheng2; Wang, Shumei1; Zhang, Weidong2,3
KeywordAlantolactone Isoalantolactone Glutathione Cysteine Conjugation Metabolism
Source PublicationJOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
2018
ISSN1570-0232
DOI10.1016/j.jchromb.2017.11.039
Volume1072Pages:370-378
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
WOS SubjectBiochemical Research Methods ; Chemistry, Analytical
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS KeywordSESQUITERPENE LACTONES ; INULA-HELENIUM ; RADIX-INULAE ; GLUTATHIONE ; CHROMATOGRAPHY ; PLASMA
AbstractAlantolactone (AL) and isoalantolactone (IAL), two major active sesquiterpene lactones isolated from Radix Inulae extract, have a wide range of pharmacological activities. The predominant metabolic pathway of AL and IAL observed was glutathione (GSH) conjugation in vitro, which could occur in the absence of metabolic enzymes. Non-enzymatic conjugation with cysteine (Cys) couldalso be observed. Four metabolites (AL-GSH, AL-Cys, IAL-GSH, IAL-Cys) were subsequently isolated and confirmed by nuclear magnetic resonance (NMR). The results indicated that the thiol of GSH or Cys can be reacted with the exomethylene carbon atoms of a, 13 unsaturated carbonyl of AL and IAL. After intravenous administration in rats, AL and IAL were extensively metabolized, and the exposure, as measured by area under the concentration-time curve (AUC), for AL-GSH, AL-Cys, IAL-GSH, and IAL-Cys was approximately 1.54-, 0.96-, 1.50-, and 0.91-fold that of the parent drug, respectively. The AUC ratio of metabolites to parent compounds of oral administration was 3.66-, 9.19-, 12.97-, and 9.92-fold that of the parent drug for the above metabolites, respectively. The bioavailability of AL-total (AL, AL-GSH, AL-Cys) and IAL-total (IAL, IAL-GSH, IAL-Cys) was, respectively, 8.39% and 13.07%, which was 3.62 and 6.95- fold that of AL (2.32%) and IAL (1.88%), respectively. The oral exposure will be underestimated if the parent drugs are tested alone. These findings provide useful information for preclinical safety evaluation, and for predicting AL and IAL metabolism in humans.
Language英语
WOS IDWOS:000423637600048
PublisherELSEVIER SCIENCE BV
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/168605
Collection中国科学院大连化学物理研究所
Corresponding AuthorWang, Shumei; Zhang, Weidong
Affiliation1.Guangdong Pharmaceut Univ, Sch Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China
2.Second Mil Med Univ, Sch Pharm, Dept Nat Prod Chem, Shanghai, Peoples R China
3.Shanghai Inst Pharmaceut Ind, Dept Pharm, Shanghai, Peoples R China
4.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
Recommended Citation
GB/T 7714
Zhou, Bailun,Ye, Ji,Yang, Niao,et al. Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: Thiol conjugation as a potential metabolic pathway[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2018,1072:370-378.
APA Zhou, Bailun.,Ye, Ji.,Yang, Niao.,Chen, Liping.,Zhuo, Zhiguo.,...&Zhang, Weidong.(2018).Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: Thiol conjugation as a potential metabolic pathway.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1072,370-378.
MLA Zhou, Bailun,et al."Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: Thiol conjugation as a potential metabolic pathway".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1072(2018):370-378.
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