St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.
Clin Transl Sci
; 17(5): e13804, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38700454
ABSTRACT
St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [11C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [11C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phloroglucinol
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Terpenes
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Plant Extracts
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Blood-Brain Barrier
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Terfenadine
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Hypericum
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Positron-Emission Tomography
Limits:
Adult
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Female
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Humans
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Male
Language:
En
Journal:
Clin Transl Sci
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: