Pharmacokinetic Characterization and Bioavailability Barrier for the Key Active Components of Botanical Drug Antitumor B (ATB) in Mice for Chemoprevention of Oral Cancer
This study aims to characterize the pharmacokinetic (PK) profiles and identify important bioavailability barriers and pharmacological pathways of the key active components (KACs) of Antitumor B (ATB), a chemopreventive agent. KACs (matrine, dictamine, fraxinellone, and maackiain) of ATB were confirmed using the antiproliferative assay and COX-2 inhibition activities in oral cancer cells. The observed in vitro activities of KACs were consistent with their cell signaling pathways predicted using the in silico network pharmacology approach. The pharmacokinetics of KACs were determined after i.v., i.p., and p.o. delivery using ATB extract and a mixture of four KACs in mice. Despite good solubilities and permeabilities, poor oral bioavailabilities were estimated for all KACs, mostly because of first-pass metabolism in the liver (for all KACs) and intestines (for matrine and fraxinellone). Multiple-dose PK studies showed 23.2-fold and 8.5-fold accumulation of dictamine and maackiain in the blood, respectively. Moreover, saliva levels of dictamine and matrine were found significantly higher than their blood levels. In conclusion, the systemic bioavailabilities of ATB-KACs were low, but significant levels of dictamine and matrine were found in saliva upon repeated oral administration. Significant salivary concentrations of matrine justified its possible use as a drug-monitoring tool to track patient compliance during chemoprevention trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
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| Enthalten in: |
Journal of natural products - 84(2021), 9 vom: 24. Sept., Seite 2486-2495 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bui, Dinh [VerfasserIn] |
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| Links: |
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| Themen: |
28808-62-0 |
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| Anmerkungen: |
Date Completed 08.12.2021 Date Revised 29.10.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jnatprod.1c00501 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330058452 |
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| 245 | 1 | 0 | |a Pharmacokinetic Characterization and Bioavailability Barrier for the Key Active Components of Botanical Drug Antitumor B (ATB) in Mice for Chemoprevention of Oral Cancer |
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| 500 | |a Date Revised 29.10.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a This study aims to characterize the pharmacokinetic (PK) profiles and identify important bioavailability barriers and pharmacological pathways of the key active components (KACs) of Antitumor B (ATB), a chemopreventive agent. KACs (matrine, dictamine, fraxinellone, and maackiain) of ATB were confirmed using the antiproliferative assay and COX-2 inhibition activities in oral cancer cells. The observed in vitro activities of KACs were consistent with their cell signaling pathways predicted using the in silico network pharmacology approach. The pharmacokinetics of KACs were determined after i.v., i.p., and p.o. delivery using ATB extract and a mixture of four KACs in mice. Despite good solubilities and permeabilities, poor oral bioavailabilities were estimated for all KACs, mostly because of first-pass metabolism in the liver (for all KACs) and intestines (for matrine and fraxinellone). Multiple-dose PK studies showed 23.2-fold and 8.5-fold accumulation of dictamine and maackiain in the blood, respectively. Moreover, saliva levels of dictamine and matrine were found significantly higher than their blood levels. In conclusion, the systemic bioavailabilities of ATB-KACs were low, but significant levels of dictamine and matrine were found in saliva upon repeated oral administration. Significant salivary concentrations of matrine justified its possible use as a drug-monitoring tool to track patient compliance during chemoprevention trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Alkaloids |2 NLM | |
| 650 | 7 | |a Antitumor B |2 NLM | |
| 650 | 7 | |a Benzofurans |2 NLM | |
| 650 | 7 | |a Drugs, Chinese Herbal |2 NLM | |
| 650 | 7 | |a Pterocarpans |2 NLM | |
| 650 | 7 | |a Quinolines |2 NLM | |
| 650 | 7 | |a Quinolizines |2 NLM | |
| 650 | 7 | |a fraxinellone |2 NLM | |
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| 650 | 7 | |a dictamnine |2 NLM | |
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| 650 | 7 | |a inermin |2 NLM | |
| 650 | 7 | |a TF360D25IJ |2 NLM | |
| 650 | 7 | |a Matrines |2 NLM | |
| 700 | 1 | |a Yin, Taijun |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Shengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Peiying |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Stuart J |e verfasserin |4 aut | |
| 700 | 1 | |a You, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Rashim |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Ming |e verfasserin |4 aut | |
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