Effects of Curcuma spp. on P-glycoprotein function.

Area of Science:

• Pharmacology
• Natural Products Chemistry
• Drug Metabolism

Background:

• Intestinal efflux transporters, particularly P-glycoprotein (P-gp), play a crucial role in limiting oral drug bioavailability.
• Curcuma longa (turmeric) and its compounds are widely used in traditional medicine and are known to possess various biological activities.
• Understanding the interaction of natural compounds with drug transporters is essential for predicting drug efficacy and safety.

Purpose of the Study:

• To investigate the in vitro effects of Curcuma longa and Curcuma sp. "khamin-oi" extracts, and their major curcuminoids on intestinal P-gp function.
• To determine whether curcumin, demethoxycurcumin, and bisdemethoxycurcumin modulate P-gp-mediated drug transport.
• To explore the potential impact of these turmeric components on the pharmacokinetics of P-gp substrate drugs.

Main Methods:

• In vitro evaluation using Caco-2 cell models to assess R123 accumulation and efflux.
• Transport studies with daunorubicin across cell monolayers.
• Analysis of calcein-AM uptake in a human P-gp overexpressing cell line (LLC-GA5-COL300).

Main Results:

• Both Curcuma longa and Curcuma sp. "khamin-oi" extracts increased R123 accumulation and decreased R123 efflux ratios in Caco-2 cells.
• Curcumin, demethoxycurcumin, and bisdemethoxycurcumin affected daunorubicin transport.
• Curcumin and demethoxycurcumin increased calcein-AM uptake in LLC-GA5-COL300 cells, indicating P-gp inhibition, while bisdemethoxycurcumin showed different effects, possibly involving other transporters like MRP.

Conclusions:

• Curcumin and demethoxycurcumin inhibit P-gp, suggesting a role in modulating the pharmacokinetics of orally administered P-gp substrate drugs.
• Bisdemethoxycurcumin may influence other efflux transporters, such as MRP.
• Curcuma longa and Curcuma sp. "khamin-oi" possess compounds that interact with intestinal drug efflux transporters, impacting drug absorption.