Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: Thiol conjugation as a potential metabolic pathway
文献类型：期刊论文
| 作者 | Zhou, Bailun1; Ye, Ji2; Yang, Niao2; Chen, Liping2; Zhuo, Zhiguo2; Mao, Ling2; Liu, Qun2; Lan, Gongcai1; Ning, Jing4; Ge, Guangbo4 |
| 刊名 | JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
 |
| 出版日期 | 2018 |
| 卷号 | 1072页码:370-378 |
| 关键词 | Alantolactone Isoalantolactone Glutathione Cysteine Conjugation Metabolism |
| ISSN号 | 1570-0232 |
| DOI | 10.1016/j.jchromb.2017.11.039 |
| 文献子类 | Article |
| 英文摘要 | Alantolactone (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. |
| WOS关键词 | SESQUITERPENE LACTONES ; INULA-HELENIUM ; RADIX-INULAE ; GLUTATHIONE ; CHROMATOGRAPHY ; PLASMA |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000423637600048 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/168604]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Wang, Shumei; Zhang, Weidong |
| 作者单位 | 1.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 |
| 推荐引用方式 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. |
入库方式： OAI收割
来源：大连化学物理研究所
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