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Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate
Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635734/ https://www.ncbi.nlm.nih.gov/pubmed/34867382 http://dx.doi.org/10.3389/fphar.2021.761884 |
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author | Chen, Bing Luo, Hongbin Chen, Weiying Huang, Qishu Zheng, Kaifan Xu, Dafen Li, Shaoguang Liu, Ailin Huang, Liying Zheng, Yanjie Lin, Xinhua Yao, Hong |
author_facet | Chen, Bing Luo, Hongbin Chen, Weiying Huang, Qishu Zheng, Kaifan Xu, Dafen Li, Shaoguang Liu, Ailin Huang, Liying Zheng, Yanjie Lin, Xinhua Yao, Hong |
author_sort | Chen, Bing |
collection | PubMed |
description | Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and in silico methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30–60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics. |
format | Online Article Text |
id | pubmed-8635734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86357342021-12-02 Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate Chen, Bing Luo, Hongbin Chen, Weiying Huang, Qishu Zheng, Kaifan Xu, Dafen Li, Shaoguang Liu, Ailin Huang, Liying Zheng, Yanjie Lin, Xinhua Yao, Hong Front Pharmacol Pharmacology Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and in silico methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30–60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics. Frontiers Media S.A. 2021-11-17 /pmc/articles/PMC8635734/ /pubmed/34867382 http://dx.doi.org/10.3389/fphar.2021.761884 Text en Copyright © 2021 Chen, Luo, Chen, Huang, Zheng, Xu, Li, Liu, Huang, Zheng, Lin and Yao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Chen, Bing Luo, Hongbin Chen, Weiying Huang, Qishu Zheng, Kaifan Xu, Dafen Li, Shaoguang Liu, Ailin Huang, Liying Zheng, Yanjie Lin, Xinhua Yao, Hong Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate |
title | Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate |
title_full | Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate |
title_fullStr | Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate |
title_full_unstemmed | Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate |
title_short | Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate |
title_sort | pharmacokinetics, tissue distribution, and human serum albumin binding properties of delicaflavone, a novel anti-tumor candidate |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635734/ https://www.ncbi.nlm.nih.gov/pubmed/34867382 http://dx.doi.org/10.3389/fphar.2021.761884 |
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