Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Autor: Guo F; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China., Xu F; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China. Electronic address: xufeng_pharm@163.com., Yu JH; Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd, Jiangsu 214145, PR China., Zou JG; Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd, Jiangsu 214145, PR China., Xue BJ; Institute for Brain Disorders, Beijing University of Chinese Medicine, No.5 Haiyuncang, Beijing 100700, PR China., Shang MY; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China., Liu GX; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China., Zhu Y; Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd, Jiangsu 214145, PR China., Gan GF; Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd, Jiangsu 214145, PR China., Rao XL; Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd, Jiangsu 214145, PR China., Wang X; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China., Gao Y; Institute for Brain Disorders, Beijing University of Chinese Medicine, No.5 Haiyuncang, Beijing 100700, PR China; Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, PR China., Cai SQ; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38, Xueyuan Road, Beijing 100191, PR China. Electronic address: sqcai@bjmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Sep 15; Vol. 248, pp. 116288. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1016/j.jpba.2024.116288
Abstrakt: Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.
Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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