Evaluation of Drug Interaction Potential of the Constituents of Labisia pumila

Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used to induce labor. In addition, it is also used to treat respiratory tract infections, menstrual and rheumatic disorders. The plant has been reported to have antioxidant, anti-inflammatory and anticancer properties. This study was developed to evaluate the possibility of any herb-drug interaction if dietary supplements containing Labisia pumila were co-administered with conventional drugs. To accomplish this goal, in vitro assays were utilized to identify constituents isolated from Labisia pumila that affect the activities of CYPs, P-gp, or PXR. Cytochrome P450 s (CYPs) are the primary drug metabolizing enzymes that are involved in the metabolism of most of the drugs. Efflux transporters such as P-glycoprotein (P-gp) have also been shown to alter the pharmacokinetic and pharmacodynamic properties of drugs. Pregnane X receptor (PXR), a type of nuclear receptor, has been implicated in transcriptional regulation of CYPs and P-gp. Methanolic extract of Labisia pumila and 13 constituents belonging to triterpenes and polyphenols class were tested. Inhibition of CYP3A4, 2D6, 1A2, and 2C19 was determined by employing C-DNA baculovirus expressed enzymes and fluorescence substrates. Inhibition of P-gp was determined in hMDR1-MDCK-II and MDCK-II cells. Modulation of PXR activity is monitored in HepG2 cell line through a reporter gene assay. The methanolic extract showed activity in all the assays. Seven compounds showed inhibition of CYPS and PXR while P-gp inhibition was observed with 4 compounds. Three compounds showed activation of PXR. In conclusion, constituents from Kacip Fatimah showed significant modulation of three important regulatory proteins (PXR, CYPs and P-gp) that could result in alteration of pharmacokinetic and pharmacodynamic properties of concomitantly administered drugs. Acknowledgements: The United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58 – 6408 – 02 – 1-612, the FDA “Science Based Authentication of Dietary Supplements” award number 5U01FD004246 are acknowledged for partial support of this work. References: [1] Mitra K, et al. (2006) Life Sci, 78: 2131 – 2145. [2] Kliewer SA, et al. (2006) Nature Rev, 1: 259 – 266 [3] Herington A, et al. (2007) Drug Discov Today, 12: 664 – 673 [3] Polli JW, et al. (2001) J Pharmacol and Exper Biol 299: 620 – 628.