P-glycoprotein-mediated herb-drug interaction evaluation between Tenacissoside G and paclitaxel

Area of Science:

• Pharmacology
• Drug Metabolism
• Natural Products Chemistry

Background:

• P-glycoprotein (P-gp) mediates herb-drug interactions (HDIs), affecting drug efficacy and safety.
• Tenacissoside G (Tsd-G), from Marsdenia tenacissima, possesses anticancer properties.

Purpose of the Study:

• To investigate the pharmacokinetic effects of Tsd-G on paclitaxel (PTX) in rats.
• To explore the potential role of P-gp in mediating HDIs between Tsd-G and PTX.

Main Methods:

• Rats received Tsd-G (20-60 mg/kg) or controls for seven days, followed by intravenous PTX (6 mg/kg).
• Plasma PTX concentrations were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
• P-gp binding and expression inhibition by Tsd-G were analyzed.

Main Results:

• Tsd-G administration significantly prolonged the mean residence time of PTX.
• Tsd-G demonstrated stable binding to P-gp via hydrogen bonds.
• Tsd-G inhibited P-gp expression in rat liver.

Conclusions:

• Tsd-G exhibits herb-drug interactions with PTX, likely mediated by P-gp.
• Tsd-G's inhibition of P-gp may alter PTX pharmacokinetics, influencing its therapeutic potential and safety profile.