Journal
CURRENT DRUG METABOLISM
Volume 22, Issue 14, Pages 1103-1113Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389200223666211216142904
Keywords
Herbal medicine; P-glycoprotein; herb-drug interaction; CYP enzymes; enzyme induction; human hepatocytes
Funding
- Fulbright Foreign Students Scholarship
- National Institutes of Health [P42ES027706]
- National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
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This study evaluated the potential herb-drug interactions of V. amygdalina, O. gratissimum, M. oleifera, A. indica, and P. nitida extracts. The results suggested that these herbal extracts can modulate CYP enzymes and P-gp activity, potentially causing herb-drug interactions in vivo.
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: 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: 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 US FDA drug interaction guidance. Result: 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 (IC50: 3.8 and 5.4 mu g/mL), respectively, while V. amygdalina and M. oleifera methanol extracts showed moderate P-gp inhibition (IC50: 12.1 and 37.2 mu g/mL, respectively). Conclusion: 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.
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