The essential oil from the fruits of Peucedanum oreoselinum (L.) Moench (Apiaceae) as a natural source of P-glycoprotein inhibitors

Abstract

P-glycoprotein (P-gp) is an efflux transporter which plays an important role in cell detoxification processes. However, it contributes to multidrug resistance (MDR) by extruding xenobiotics from cells. Research on P-gp inhibitors of natural origin is receiving growing attention due to their structural diversity and drug potential. Several natural compounds have been signalled for their ability to inhibit P-gp. Extracts from Peucedanum species proved to reduce P-gp expression. Data on the chemistry of Peucedanum oreoselinum (L.) Moench is scarce. The composition of the essential oil, isolated by hydrodistillation in a Clevenger type apparatus, from fruits of P. oreoselinum from Portugal, was determined. The essential oil and some of its constituents were tested for their effect on P-gp-mediated efflux in vitro. The essential oil composition was elucidated by gas chromatography and gas chromatography-mass spectrometry, and the effects on P-gp were determined by the intracellular accumulation of Rhodamine 123. The essential oil is mainly composed of monoterpene hydrocarbons (94.9%), and its major constituents are limonene (17.9%), α-pinene (17.7%), sabinene (16.5%), β-pinene (14.4%) and Z-ocimene (12.9%). The essential oil, as well as myrcene, a minor constituent, displayed an inhibitory effect on P-gp. The composition of the essential oil is different from that reported in the literature. This is the first report on the P-gp inhibition potential of this essential oil and myrcene, even though other essential oils and terpenic compounds have already demonstrated inhibitory activity, according to previous works. Our study expands the available information on the phytochemistry of P. oreoselinum, and our findings contribute to consolidate the anti-MDR potential of natural products.