Division of Clinical Pharmacology, University of Stellenbosch, Cape Town, South Africa; National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Division of Pharmacology, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Synexa Life Sciences, Montague Gardens, Division of Medical Microbiology, University of Stellenbosch, Cape Town, South Africa
Awortwe, C., Division of Clinical Pharmacology, University of Stellenbosch, Cape Town, South Africa; Manda, V.K., National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Avonto, C., National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Khan, S.I., National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United States, Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Khan, I.A., National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United States, Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Walker, L.A., National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United States, Division of Pharmacology, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United States; Bouic, P.J., Synexa Life Sciences, Montague Gardens, Division of Medical Microbiology, University of Stellenbosch, Cape Town, South Africa; Rosenkranz, B., Division of Clinical Pharmacology, University of Stellenbosch, Cape Town, South Africa
Kalanchoe crenata popularly known as “dog’s liver” is used in most African countries for the treatment of chronic diseases such as diabetes, asthma and HIV/AIDS related infections. The evaluation of K. crenata for herb-drug interactions has not been reported. This study therefore aims to evaluate the risk of K. crenata for herb-drug interaction in vitro. Crude methanol and fractions of K. crenata were incubated and preincubated with recombinant human CYP2C19 and CYP3A4. Comparative studies were conducted in both human liver microsomes and recombinant human CYP to ascertain the inhibition profile of the crude extract and the various fractions. The cocktail approach of recombinant human CYPs was conducted to confirm the inhibition potential of the fractions in the presence of other CYPs. The results showed significant time-dependent inhibition of tested samples on CYP3A4 with crude methanol (39KC), fractions 45A, 45B and 45D given IC<inf>50</inf> fold decrease of 3.29, 2.26, 1.91 and 1.49, respective. Time dependent kinetic assessment of 39KC and 45D showed K<inf>I</inf> and k<inf>inact</inf> values for 39KC as 1.77μg/mL and 0.091 min−1 while that of 45D were 6.45 μg/mL and 0.024 min−1, respectively. Determination of k<inf>inact</inf> based on IC<inf>50</inf> calculations yielded 0.015 and 0.04 min−1 for 39KC and 45D, respectively. Cocktail approach exhibited fold decreases in IC<inf>50</inf> for all test fractions on CYP3A4 within the ranges of 2.10 – 4.10. At least one phytoconstituent in the crude methanol extract of Kalanchoe crenata is a reversible and time-dependent inhibitor of CYP3A4. © 2015 Bentham Science Publishers.