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Herbal modulation of P-glycoprotein
Shufeng Zhou1, Lee Yong Lim, Balram Chowbay
1Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore. phazsf@nus.edu.sg
Drug Metabolism Reviews
|April 10, 2004
Summary
Herbal constituents modulate P-glycoprotein (Pgp), affecting drug absorption and bioavailability. Understanding these interactions is crucial for safe and effective herbal medicine use and drug therapy.
Area of Science:
- Pharmacology
- Biochemistry
- Natural Products Chemistry
Background:
- P-glycoprotein (Pgp), a key transporter encoded by the MDR1 gene, influences the disposition of numerous xenobiotics, including drugs and toxins.
- Pgp is expressed in vital organs like the intestine, liver, kidney, and brain, playing a significant role in barrier functions and drug elimination.
- Herbal constituents, similar to cytochrome P450 enzymes (CYP3A4), can interact with Pgp, leading to modulation of its activity and expression.
Purpose of the Study:
- To investigate the modulatory effects of various herbal constituents on P-glycoprotein (Pgp) activity and expression.
- To elucidate the mechanisms by which herbal compounds interact with Pgp, including direct binding and receptor activation.
- To assess the clinical implications of Pgp modulation by herbs on drug bioavailability and potential herb-drug interactions.
Main Methods:
- Utilized ATPase assays with purified Pgp protein and Pgp-expressing cells to assess modulatory effects.
- Employed specific probe substrates and inhibitors to quantify Pgp activity.
- Investigated in vitro and in vivo models to study Pgp induction and modulation by herbal constituents.
Main Results:
- Identified several herbal compounds, including curcumin, piperine, and silymarin, as Pgp inhibitors.
- Demonstrated that certain catechins can enhance Pgp-mediated transport, while St. John's wort induces intestinal Pgp expression.
- Observed that flavonoids like quercetin can directly interact with Pgp binding sites, and compounds like hyperforin activate the pregnane X receptor.
Conclusions:
- Herbal constituents significantly modulate Pgp activity and expression, impacting drug bioavailability and potentially reversing multidrug resistance.
- The modulation of Pgp by herbs, alongside CYP3A4 interactions, represents a critical mechanism in clinically relevant herb-drug interactions.
- Further research is essential to fully understand the interplay between Pgp, CYP3A4, and herbal components for optimizing therapeutic outcomes.