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Article: A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain

TitleA Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain
Authors
Keywordschlorogenic acid
distribution
neuroprotection
pharmacokinetics
UHPLC–MS/MS
Issue Date24-Jan-2023
PublisherMDPI
Citation
Pharmaceuticals, 2023, v. 16, n. 2 How to Cite?
Abstract

Chlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics and distribution in the rat brain remain unclear. In this study, we established a rapid and sensitive UHPLC–MS/MS method for the determination of 5-CQA in rat plasma, cerebrospinal fluid (CSF), and brain tissue to investigate whether it could pass through the blood–brain barrier (BBB) and its distribution in the rat brain, and a Caenorhabditis elegans (C. elegans) strain paralysis assay was used to investigate the neuroprotective effect of 5-CQA in different brain tissues. Chromatographic separation of 5-CQA and glycyrrhetinic acid (GA, used as internal standard) was completed in 0.5 min, and the full run time was maintained at 4.0 min. Methodological validation results presented a high accuracy (95.69–106.81%) and precision (RSD ≤ 8%), with a lower limit of quantification of 1.0 ng/mL. Pharmacokinetic results revealed that 5-CQA can pass through the BBB into the CSF, but the permeability of BBB to 5-CQA (ratio of mean AUC0-∞ of CSF to plasma) was only approximately 0.29%. In addition, 5-CQA can penetrate into the rat brain extensively and is distributed with different intensities in different nuclei. A C. elegans strain paralysis assay indicated that the neuroprotective effect of 5-CQA is positively correlated with its content in different brain tissues. In conclusion, our study for the first time explored the BBB pass rate and brain tissue distribution of 5-CQA administered via the tail vein by the UHPLC–MS/MS method and investigated the potential main target area of 5-CQA for neuroprotection, which could provide a certain basis for the treatment of nervous system-related diseases of 5-CQA.


Persistent Identifierhttp://hdl.handle.net/10722/339098
ISSN
2023 Impact Factor: 4.3
2023 SCImago Journal Rankings: 0.845
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBai, Chongfei-
dc.contributor.authorZhou, Xiaogang-
dc.contributor.authorYu, Lu-
dc.contributor.authorWu, Anguo-
dc.contributor.authorYang, Le-
dc.contributor.authorChen, Jianping-
dc.contributor.authorTang, Xue-
dc.contributor.authorZou, Wenjun-
dc.contributor.authorWu, Jianming-
dc.contributor.authorZhu, Linjie-
dc.date.accessioned2024-03-11T10:33:53Z-
dc.date.available2024-03-11T10:33:53Z-
dc.date.issued2023-01-24-
dc.identifier.citationPharmaceuticals, 2023, v. 16, n. 2-
dc.identifier.issn1424-8247-
dc.identifier.urihttp://hdl.handle.net/10722/339098-
dc.description.abstract<p>Chlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics and distribution in the rat brain remain unclear. In this study, we established a rapid and sensitive UHPLC–MS/MS method for the determination of 5-CQA in rat plasma, cerebrospinal fluid (CSF), and brain tissue to investigate whether it could pass through the blood–brain barrier (BBB) and its distribution in the rat brain, and a Caenorhabditis elegans (C. elegans) strain paralysis assay was used to investigate the neuroprotective effect of 5-CQA in different brain tissues. Chromatographic separation of 5-CQA and glycyrrhetinic acid (GA, used as internal standard) was completed in 0.5 min, and the full run time was maintained at 4.0 min. Methodological validation results presented a high accuracy (95.69–106.81%) and precision (RSD ≤ 8%), with a lower limit of quantification of 1.0 ng/mL. Pharmacokinetic results revealed that 5-CQA can pass through the BBB into the CSF, but the permeability of BBB to 5-CQA (ratio of mean AUC<sub>0-∞</sub> of CSF to plasma) was only approximately 0.29%. In addition, 5-CQA can penetrate into the rat brain extensively and is distributed with different intensities in different nuclei. A C. elegans strain paralysis assay indicated that the neuroprotective effect of 5-CQA is positively correlated with its content in different brain tissues. In conclusion, our study for the first time explored the BBB pass rate and brain tissue distribution of 5-CQA administered via the tail vein by the UHPLC–MS/MS method and investigated the potential main target area of 5-CQA for neuroprotection, which could provide a certain basis for the treatment of nervous system-related diseases of 5-CQA.</p>-
dc.languageeng-
dc.publisherMDPI-
dc.relation.ispartofPharmaceuticals-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectchlorogenic acid-
dc.subjectdistribution-
dc.subjectneuroprotection-
dc.subjectpharmacokinetics-
dc.subjectUHPLC–MS/MS-
dc.titleA Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain-
dc.typeArticle-
dc.identifier.doi10.3390/ph16020178-
dc.identifier.scopuseid_2-s2.0-85148952465-
dc.identifier.volume16-
dc.identifier.issue2-
dc.identifier.eissn1424-8247-
dc.identifier.isiWOS:000940563300001-
dc.identifier.issnl1424-8247-

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