Screening for Chemosensitizers from Natural Plant Extracts through the Inhibition Mechanism of P-glycoprotein

Abstract

ABSTRACT − P-gp plays a critical role in drug disposition and represents a mechanism for the development of multidrugresistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shownto inhibit P-gp. Therefore, the aim of this study was to identify new candidate chemosensitizers by screening various plantextracts. The ability of natural plant extracts to inhibit P-gp activity was assessed by measuring cellular accumulation of cal-cein AM, daunorubicin and vincristine in P-gp overexpressing MDCKII-MDR1 cells. Among more than 800 plant extracts,eight were found to inhibit P-gp activity. Curcuma aromatica extract produced greatest inhibition, followed by Curcumalonga and Dalbergia odorifera extracts. Extracts of Aloe ferox, Curcuma zedoariae rhizome, Zanthoxylum planispinum, andAgeratum conyzoides showed moderate inhibitory effects. Curcumin and quercetin exhibited similar inhibition of P-gp-mediated efflux of daunorubicin and vincristine, and flavones had a lesser effect. When chemosensitizing effect was eval-uated by measuring daunorubicin sensitivity to MDCKII-MDR1 cells in the presence of natural plant extracts, Curcuma aro-matica showed the most potent chemosensitizing effect based on daunorubicin cytotoxicity. In conclusion, natural plantextracts such as Curcuma aromatica can potently inhibit P-gp activity and may have potential as a novel chemosensitizers. Key words