title: In Vitro Reversible and Time-Dependent CYP450 Inhibition Profiles of Medicinal Herbal Plant Extracts Newbouldia laevis and Cassia abbreviata: Implications for Herb-Drug Interactions.
abstract: This study evaluated the effects of Newbouldia laevis and Cassia abbreviata extracts on CYP450 enzyme activity. Recombinant CYP450 enzyme and fluorogenic substrates were used for evaluating inhibition, allowing the assessment of herb-drug interactions (HDI). Phytochemical fingerprinting was performed using UPLC-MS. The herbal extracts were risk ranked for HDI based on the IC50 values determined for each CYP enzyme. Newbouldia laevis inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities with Ki of 2.84 µg/mL, 1.55 µg/mL, and 1.23 µg/mL, respectively. N. laevis exhibited a TDI (4.17) effect on CYP1A2 but not CYP2C9 and CYP2C19 enzyme activities. Cassia abbreviata inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities showing a Ki of 4.86 µg/mL, 5.98 µg/mL, and 1.58 µg/mL, respectively. TDI potency assessment for Cassia abbreviata showed it as a potential TDI candidate (1.64) for CYP1A2 and CYP2C19 (1.72). UPLC-MS analysis showed that Newbouldia laevis and Cassia abbreviata possess polyphenols that likely give them their therapeutic properties; some of them are likely to be responsible for the observed inhibition. The observations made in this study suggest the potential for these herbal compounds to interact, especially when co-administered with other medications metabolized by these CYP450 enzymes.
authors.affiliation: Division of Human Genetics, Department of Pathology &amp; Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. thmnic023@myuct.ac.za.|School of Medical Sciences, University of Cape Coast, Cape Coast, PMB, Ghana. thmnic023@myuct.ac.za.
authors.forename: Nicholas Ekow
authors.initials: NE
authors.lastname: Thomford
authors.affiliation: ICGEB, Cape Town Component, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. kd.dzobo@uct.ac.za.|Division of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. kd.dzobo@uct.ac.za.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dzobo
authors.affiliation: Division of Medical Virology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. denis.chopera@uct.ac.za.
authors.forename: Denis
authors.initials: D
authors.lastname: Chopera
authors.affiliation: Division of Human Genetics, Department of Pathology &amp; Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. ambroise.wonkam@uct.ac.za.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
authors.affiliation: Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa. amaroyi@ufh.ac.za.
authors.forename: Alfred
authors.initials: A
authors.lastname: Maroyi
authors.affiliation: Division of Chemical Pathology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. dee.blackhurst@uct.ac.za.
authors.forename: Dee
authors.initials: D
authors.lastname: Blackhurst
authors.affiliation: Division of Human Genetics, Department of Pathology &amp; Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. collet.dandara@uct.ac.za.
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
mesh_terms: D001682:Biological Availability; D002366:Cassia / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D041743:Herb-Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D000068378:Lamiales / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts
keywords: CYP450; Cassia abbreviata; IC50; Newbouldia laevis; rCYP; time-dependent inhibition (TDI)