New potent P-glycoprotein
modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells.
Possessing antioxidant, radical scavenging, anti-inflammatory, and antiatherosclerotic capabilities, quercetin is also an inhibitor of CYP3A4 as well as a modulator of P-glycoprotein
. Quercetin has been observed to enhance the bioavailability of and--therefore--increase the therapeutic efficacy of a number of drugs: epigallocatechin gallate (an anticancer component of green tea), diltiazem (used to treat angina pectoris, hypertension, and some types of arrhythmia), and digoxin (widely used for atrial fibrillation, atrial flutter, and heart failure) to name a few (45-48).
Other transporters such as P-glycoprotein
are involved in the hepatocyte transport of drugs.
Amiodarone and its main metabolite N-desethylamiodarone (NDEA) inhibit CYP3A4 and P-glycoprotein
resulting in supratherapeutic concentrations of rivaroxaban when used simultaneously.
Tanaka, "Disease control by regulation of P-glycoprotein
on lymphocytes in patients with rheumatoid arthritis," World Journal of Experimental Medicine, vol.
Some studies demonstrated reductions in drug levels of up to 50% with strong CYP3A4 and P-glycoprotein
Therefore, BDMCur, DMCur and Cur may be the substrates of P-glycoprotein
and MRP2; the transport mechanism of BDMCur, DMCur and Cur is the active transport in the carrier-mediated transport.
(7,8) These increases are caused by several mechanisms, but the 2 most important may be inhibition of intestinal P-glycoprotein
and increases in small intestine absorption surfaces (Table 2).
Interaction of cytochrome P450 3A inhibitors with P-glycoprotein
. J Pharmacol Exp Ther 2002; 303:323-332.
According to Ronald Cannon, Ph.D., staff scientist at NIHs National Institute of Environmental Health Sciences (NIEHS), the biggest obstacle to efficiently delivering drugs to the brain is a protein pump called P-glycoprotein
. Located along the inner lining of brain blood vessels, P-glycoprotein
directs toxins and pharmaceuticals back into the bodys circulation before they pass into the brain.
Research shows that natural compounds can reverse drug resistance by inhibition of P-glycoprotein
, inhibition of glutathione S-transferase drug detoxification system and inhibition of heat-shock proteins.
Background/Aims: Helicobacter pylori is a carcinogenic bacterium that could induce P-glycoprotein
expression in the human gastrointestinal tract.
Akagi, "Upregulation of P-glycoprotein
expression by osmotic stress in rat sugar cataract," Experimental Eye Research, vol.
One of the well-known ABC transporters is PGP (P-glycoprotein
, gene symbol ABCB1), which is called a molecular "hydrophobic vacuum cleaner." PGP is pulling substrates from the membrane and expelling them to promote multidrug resistance .
Giugliano, "The P-glycoprotein
transport system and cardiovascular drugs," Journal of the American College of Cardiology, vol.