Evaluation of drug interaction potential of Labisia pumila (Kacip Fatimah) and its constituents
Frontiers in Pharmacology
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS 38677, United States; Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, MS 38677, United States; Department of Pharmacology, School of Pharmacy, The University of Mississippi, MS 38677, United States; Division of Clinical Pharmacology, University of Stellenbosch, Cape Town, South Africa
Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used in a number of women's health applications such as to improve libido, relieve postmenopausal symptoms, and to facilitate or hasten delivery in childbirth. In addition, the constituents of this plant have been reported to possess anticancer, antioxidant, and anti-inflammatory properties. Clinical studies have indicated that cytochrome P450s (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR) are the three main modulators of drug-drug interactions which alter the absorption, distribution, and metabolism of drugs. Given the widespread use of Kacip Fatimah in dietary supplements, the current study focuses on determining the potential of its constituents to affect the activities of CYPs, P-gp, or PXR using in vitro assays which may provide useful information towards the risk of herb-drug interaction with concomitantly used drugs. Six compounds isolated from the roots of Labisia pumila (2 saponins and 4 alkyl phenols) were tested, in addition to the methanolic extract. The extract of Labisia pumila showed a significant time dependent inhibition (TDI) of CYP3A4, reversible inhibition of CYP2C9 and 2C19 and a weak inhibition of 1A2 and 2D6 as well as an inhibition of P-gp and rifampicininduced PXR activation. The alkyl phenols inhibited CYP3A4 (TDI), CYP2C9 and 2C19 (reversible) while saponins inhibited P-gp and PXR. In conclusion, Labisia pumila and its constituents showed significant modulation of all three regulatory proteins (CYPs, P-gp and PXR) suggesting a potential to alter the pharmacokinetic and pharmacodynamic properties of conventional drugs if used concomitantly. © 2014 Manda, Dale, Awortwe, Ali, Khan, Walker and Khan.
5 (10pentadecenyl)resorcinol; alkylphenol derivative; ardisimamilloside H; belamcandol B; cyclosporin A; cytochrome P450 1A2; cytochrome P450 2C19; cytochrome P450 2C9; cytochrome P450 2D6; cytochrome P450 3A4; demethylbelamcandaquinone B; fatimahol; ketoconazole; Labisia pumila extract; methanol; multidrug resistance protein; phenol derivative; plant extract; pregnane X receptor; primulanin; rifampicin; saponin derivative; tranylcypromine; troleandomycin; unclassified drug; verapamil; animal cell; article; biochemical composition; controlled study; drug absorption; drug bioavailability; drug blood level; drug isolation; drug screening; drug structure; enzyme activity; enzyme inhibition; herb; herb drug interaction; human; human cell; in vitro study; intestine absorption; Labisia pumila; nonhuman; plant root
U01-FD004246-01, FDA, U.S. Food and Drug Administration