Comprehensive pharmacokinetic analysis of trans-crocetin and its metabolites- cis-crocetin, CM, and CD- in rats using UPLC-Q-Orbitrap-MS/MS method

IF 2.5 3区医学 Q3 CHEMISTRY, MEDICINAL

Fitoterapia Pub Date : 2025-02-26 DOI:10.1016/j.fitote.2025.106460

Ziwei Chen , Susu Lin , Zijin Xu , Ting Wang , Shaoxian Wang , Jian Zhong , Yingpeng Tong , Ping Wang , Peishi Feng

{"title":"Comprehensive pharmacokinetic analysis of trans-crocetin and its metabolites- cis-crocetin, CM, and CD- in rats using UPLC-Q-Orbitrap-MS/MS method","authors":"Ziwei Chen , Susu Lin , Zijin Xu , Ting Wang , Shaoxian Wang , Jian Zhong , Yingpeng Tong , Ping Wang , Peishi Feng","doi":"10.1016/j.fitote.2025.106460","DOIUrl":null,"url":null,"abstract":"<div><div>Crocetin, an active component of saffron (Crocus sativus L.), exhibits antidepressant, anti-tumor, and anti-diabetic effects. However, the pharmacokinetics of trans-crocetin and its metabolites, such as cis-crocetin, crocetin-monoglucuronide (CM), and crocetin-diglucuronide (CD), after intragastric (i.g.) administration of trans-crocetin in vivo remains underexplored. In the present study, a sensitive and reliable UPLC-Q-Orbitrap-MS/MS method was developed to comprehensively elucidate the preclinical pharmacokinetic patterns of trans-crocetin and the distribution characteristics of its metabolites in rats for the first time. The established UPLC-Q-Orbitrap-MS/MS method has good specificity and selectivity, with the accuracy, precision, recovery, and matrix effect meeting the methodological requirements. Pharmacokinetic analysis revealed rapid absorption of trans-crocetin into the blood, with a biphasic absorption pattern observed for trans-crocetin and CM. The absorbed trans/cis-crocetin were widely distributed in rat tissues, especially spleen, heart, adipose and lungs. Notably, trans/cis-crocetin and CM were detected simultaneously in rat brain tissue, indicating that crocetin can cross the blood-brain barrier. The CD was only detected in plasma and not in other tissues. The small intestine and liver appear to be key sites for the glucuronidation and conformational change of trans-crocetin, respectively. The elimination rates of trans/cis-crocetin and CM in tissues were significantly slower than in the blood. Trans-Crocetin was primarily excreted in feces and kidneys, while cis-crocetin and CM were cleared mainly by the kidneys. The pharmacokinetic process and tissue distribution characteristics of trans/cis-crocetin, CM, and CD were expounded in this study, which can provide a scientific basis and guidance for the further development and utilization of crocetin.</div></div>","PeriodicalId":12147,"journal":{"name":"Fitoterapia","volume":"182 ","pages":"Article 106460"},"PeriodicalIF":2.5000,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fitoterapia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0367326X25000851","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Crocetin, an active component of saffron (Crocus sativus L.), exhibits antidepressant, anti-tumor, and anti-diabetic effects. However, the pharmacokinetics of trans-crocetin and its metabolites, such as cis-crocetin, crocetin-monoglucuronide (CM), and crocetin-diglucuronide (CD), after intragastric (i.g.) administration of trans-crocetin in vivo remains underexplored. In the present study, a sensitive and reliable UPLC-Q-Orbitrap-MS/MS method was developed to comprehensively elucidate the preclinical pharmacokinetic patterns of trans-crocetin and the distribution characteristics of its metabolites in rats for the first time. The established UPLC-Q-Orbitrap-MS/MS method has good specificity and selectivity, with the accuracy, precision, recovery, and matrix effect meeting the methodological requirements. Pharmacokinetic analysis revealed rapid absorption of trans-crocetin into the blood, with a biphasic absorption pattern observed for trans-crocetin and CM. The absorbed trans/cis-crocetin were widely distributed in rat tissues, especially spleen, heart, adipose and lungs. Notably, trans/cis-crocetin and CM were detected simultaneously in rat brain tissue, indicating that crocetin can cross the blood-brain barrier. The CD was only detected in plasma and not in other tissues. The small intestine and liver appear to be key sites for the glucuronidation and conformational change of trans-crocetin, respectively. The elimination rates of trans/cis-crocetin and CM in tissues were significantly slower than in the blood. Trans-Crocetin was primarily excreted in feces and kidneys, while cis-crocetin and CM were cleared mainly by the kidneys. The pharmacokinetic process and tissue distribution characteristics of trans/cis-crocetin, CM, and CD were expounded in this study, which can provide a scientific basis and guidance for the further development and utilization of crocetin.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Fitoterapia 医学-药学

CiteScore

5.80

自引率

2.90%

发文量

198

审稿时长

1.5 months

期刊介绍： Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.