Determination of Drug Interaction Potential of the Constituents of Dioscorea villosa and Labisia pumila

Dioscorea villosa (Wild yam) is native to North America and is mainly used as a natural alternative for estrogen replacement therapy to improve women's health. Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used to induce labor. In addition, the constituents of these plants have been shown to possess anticancer, antioxidant, and anti-inflammatory properties. Clinical studies have indicated that Cytochrome P450 s (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR) are the three main modulators of drug-drug interactions. Given the wide use of Wild yam and Kacip Fatimah as dietary supplements, the current study focuses on determining the potential of its constituents to affect the activities of CYPs (3A4, 2D6, 1A2, and 2C19) P-gp, or PXR using in vitro assays which may help to predict the risk of drug interactions with concomitantly used drugs. Thirteen compounds isolated from Dioscorea villosa (steroidal saponins and steroidal glycosides) and Labisia pumila (triterpenes and polyphenols) were tested in addition to the methanolic extracts. Methanolic extract of Dioscorea villosa roots inhibited all the four CYPs and P-gp. Four compounds showed inhibition of CYPs while three showed inhibition of P-gp. No effect on PXR was observed with dioscorea extract or its constituents. The methanolic extract of Labisia pumila inhibited all the four CYPs, P-gp and rifampicin induced PXR activation. Seven compounds showed inhibition of PXR, CYPs while P-gp inhibition was observed with four constituents. Three compounds also showed activation of rifampicin induced PXR. In conclusion, constituents of Dioscorea villosa were found to modulate CYPs and P-gp activities while constituents of Labisia pumila showed significant modulation of all three regulatory proteins (PXR, CYPs and P-gp) that could result in alteration of pharmacokinetic and pharmacodynamic properties of concomitantly administered drugs.