Inhibition of P-glycoprotein ATPase and its transport function of Helicoverpa armigera by morin, quercetin and phloroglucinol

Flavonoids (morin, quercetin and phloroglucinol) were tested for their ability to modulate the function of P-glycoprotein ATPase of the insecticide resistant pest Helicoverpa armigera (Ha-Pgp). Flavonoids in the presence of ethylparaoxon or cypermethrin significantly reduced both larval weight as well as survival rate 40–50%. Morin and quercetin inhibited the activity of Ha-Pgp ATPase by 80–90%, whereas phloroglucinol inhibited ATPase activity by 40% at 100 μM concentration. These flavonoids inhibited the verapamil, ethylparaoxon and cypermethrin-stimulated Ha-Pgp ATPase activity. Morin, quercetin and phloroglucinol binding were quantitated by quenching of the intrinsic Trp fluorescence of purified Ha-Pgp ATPase. Drug transport was monitored in proteoliposomes containing Ha-Pgp ATPase using the high affinity fluorescent substrate tetramethylrosamine (TMR) in real time. Addition of the morin and quercetin mediated the collapse of the TMR concentration gradient generated by Ha-Pgp ATPase. The inhibition studies on Ha-Pgp ATPase activity may contribute towards understanding new strategies of the pest to overcome insecticide resistance.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Flavonoids inhibited the activity of Ha-Pgp ATPase activity. ► Morin and quercetin inhibited the insecticides-stimulated Ha-Pgp ATPase activity. ► Morin and quercetin interacted with Ha-Pgp with relatively high affinity. ► Morin and quercetin inhibited TMR transport into reconstituted proteoliposomes containing Ha-Pgp. ► Morin, quercetin and phloroglucinol with pesticides reduce the body weight and survival rate of Helicoverpa armigera.