A Double-Edged Sword: Focusing on Potential Drug-to-Drug Interactions of Quercetin

Herbal and herbal dietary supplements have a massive share of the global market, and their use continues to grow worldwide. There is a general perception that herbal and herbal dietary supplements are effective and safe. However, herbal formulation-drug and natural product-drug interactions are an easily overlooked issue in using herbals and herbal dietary supplements. Positive herb-drug interactions can increase the effectiveness of drugs and reduce their toxic effects. Instead, negative natural product-drug interactions can cause adverse reactions. Quercetin, a natural flavonoid, is present in the form of quercetin glycosides in herbal dietary supplements and is widely consumed by the population daily. In recent years, quercetin has demonstrated excellent biological activities such as hypotensive, hypoglycemic, antioxidant stress, anti-inflammatory, antibacterial, antiviral, and immunomodulatory, and it is widely used in the treatment of various human diseases. Numerous in vivo , in vitro , and clinical studies have revealed pharmacokinetic and pharmacodynamic interactions between quercetin and drugs. By competitively binding to serum albumin, affecting cytochrome P450, glycoproteins, organic anion transporting peptides, and glucuronidase activity, quercetin can alter the absorption, distribution, metabolism, and clearance of some drugs in vivo , affecting their pharmacokinetic profile. In addition, its pharmacodynamic interactions with many drugs have produced potentiation, toxicity reduction, or overcoming resistance in treating several diseases such as infectious diseases, chronic infectious diseases, cardiovascular diseases, diabetes, and cancer. We present a comprehensive summary of the observed pharmacokinetic and pharmacodynamic interactions of quercetin with herbal drugs. Additionally, the potential mechanisms of these interactions and directions for future related research are described. Graphical Abstract