Evaluation of Nigerian Medicinal Plants Extract on Human P-glycoprotein and Cytochrome P450 Enzyme Induction: Implications for Herb-drug Interaction.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ antagonists & inhibitors
Cells, Cultured
Chromatography, Liquid
/ methods
Cytochrome P-450 Enzyme Inducers
/ isolation & purification
Hepatocytes
/ drug effects
Herb-Drug Interactions
Humans
Inhibitory Concentration 50
Kidney
/ drug effects
Medicine, African Traditional
Nigeria
Plant Extracts
/ administration & dosage
Plants, Medicinal
/ chemistry
Tandem Mass Spectrometry
/ methods
CYP enzymes
Herbal medicine
P-glycoprotein
enzyme induction
herb-drug interaction
human hepatocytes.
Journal
Current drug metabolism
ISSN: 1875-5453
Titre abrégé: Curr Drug Metab
Pays: Netherlands
ID NLM: 100960533
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
07
2021
revised:
31
10
2021
accepted:
15
11
2021
pubmed:
18
12
2021
medline:
12
3
2022
entrez:
17
12
2021
Statut:
ppublish
Résumé
Herbal medicine represents a significant component of disease prevention and therapy in most African countries. Herb-drug interactions (HDI) can arise from the co-administration of herbal and orthodox medicines. This study assessed the potential for HDI of V. amygdalina, O. gratissimum, M. oleifera, A. indica, and P. nitida extracts using in vitro assays. Little is known about these medicinal plants' potential for drug interaction despite their extensive use in Nigeria for several disease conditions. The medicinal plant crude extracts were evaluated for Cytochrome P450 (CYP) enzyme induction using cryopreserved human hepatocytes. Enzyme activity was determined by quantifying probe substrate metabolism and metabolite formation using liquid chromatography-mass spectrometry/mass spectrometry. The extracts were evaluated for the potential to inhibit P-glycoprotein (P-gp) activity using human embryonic kidney membrane vesicles over-expressing human P-gp. The herbal extracts in vivo drug interaction potential was predicted based on the USFDA drug interaction guidance. O. gratissimum and P. nitida methanol extracts induced CYP1A2 enzyme activity by greater than 3-fold. P. nitida methanol extracts showed over 2-fold induction of CYP1A2 mRNA expression. O. gratissimum methanol extract induced CYP2B6 mRNA expression over 2-fold. P. nitida and A. indica methanol extracts showed potent inhibition of P-gp activity (IC Our studies suggested that the medicinal plants' extracts can modulate CYP enzymes and P-gp activity with the potential to cause herb-drug interaction in vivo.
Sections du résumé
BACKGROUND
BACKGROUND
Herbal medicine represents a significant component of disease prevention and therapy in most African countries. Herb-drug interactions (HDI) can arise from the co-administration of herbal and orthodox medicines.
OBJECTIVE
OBJECTIVE
This study assessed the potential for HDI of V. amygdalina, O. gratissimum, M. oleifera, A. indica, and P. nitida extracts using in vitro assays. Little is known about these medicinal plants' potential for drug interaction despite their extensive use in Nigeria for several disease conditions.
METHOD
METHODS
The medicinal plant crude extracts were evaluated for Cytochrome P450 (CYP) enzyme induction using cryopreserved human hepatocytes. Enzyme activity was determined by quantifying probe substrate metabolism and metabolite formation using liquid chromatography-mass spectrometry/mass spectrometry. The extracts were evaluated for the potential to inhibit P-glycoprotein (P-gp) activity using human embryonic kidney membrane vesicles over-expressing human P-gp. The herbal extracts in vivo drug interaction potential was predicted based on the USFDA drug interaction guidance.
RESULT
RESULTS
O. gratissimum and P. nitida methanol extracts induced CYP1A2 enzyme activity by greater than 3-fold. P. nitida methanol extracts showed over 2-fold induction of CYP1A2 mRNA expression. O. gratissimum methanol extract induced CYP2B6 mRNA expression over 2-fold. P. nitida and A. indica methanol extracts showed potent inhibition of P-gp activity (IC
CONCLUSION
CONCLUSIONS
Our studies suggested that the medicinal plants' extracts can modulate CYP enzymes and P-gp activity with the potential to cause herb-drug interaction in vivo.
Identifiants
pubmed: 34915831
pii: CDM-EPUB-119463
doi: 10.2174/1389200223666211216142904
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
Cytochrome P-450 Enzyme Inducers
0
Plant Extracts
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1103-1113Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103430
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES027706
Pays : United States
Organisme : NIH HHS
ID : P42ES027706
Pays : United States
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.