An Overview of the Evidence and Mechanism of Drug-Herb Interactions Between Propolis and Pharmaceutical Drugs

Abstract

With the growing interest in the medicinal use of propolis, numerous studies have reported significant interactions between propolis extract and pharmaceutical drugs which may result in great clinical benefits or risks. The present study aims to review the drug-herb interactions of the full-spectrum propolis extract and main pharmaceutical drugs from the pharmacodynamic and pharmacokinetic aspects and elucidate the underlying pharmacological mechanisms. A literature search was conducted between June 2021 and February 2022 in Google Scholar, PubMed, MEDLINE, and EMBASE databases to include English studies from years 2000 to 2022 that evaluated the interaction of full-spectrum propolis extract and standard pharmaceutical drugs/cytochromes P450s. Studies that looked into geopropolis, propolis fractions, and isolated compounds, or interaction of propolis with foods, bioactive molecules, or receptors other than standard pharmaceutical drugs were excluded. From a pharmacodynamic perspective, propolis extract exhibited positive or synergistic interaction with several chemotherapeutic drugs by enhancing antitumor activity, sensitizing the chemoresistance cell lines, and attenuating multi-organ toxicity. The molecular mechanisms were associated with upregulating the apoptotic signal and immunomodulatory activity and attenuating oxidative damage. Propolis extract also enhanced the anti-bacterial and antifungal activities of many antimicrobial drugs against sensitive and resistant organisms, with an effect against the gram-positive bacteria stronger than that of the gram-negative bacteria. The synergistic action was related to strengthened action on interfering cell wall integrity and protein synthesis. The strong antioxidant activity of propolis also strengthened the therapeutic effect of metformin in attenuating hyperglycemia and pancreatic damage, as well as mitigating oxidative stress in the liver, kidney, and testis. In addition, propolis showed a potential capacity to enhance short-term and long-term memory function together with donepezil and improve motor function with levodopa and parasite killing activity with praziquantel. Pharmacokinetic studies showed inhibitory activities of propolis extracts on several CYP450 enzymes in vitro and in vivo. However, the effects on those CYP450 were deemed insignificant in humans, which may be attributed to the low bioavailability of the contributing bioactive compounds when administered in the body. The enhanced bioactivities of propolis and main pharmaceutical drugs support using propolis in integrative medicine in anti-cancer, anti-microbial, antidiabetic, and neurological disorders, with a low risk of altered pharmacokinetic activities.

Keywords: CYP450; antimicrobial; chemotherapy; drug-herb interaction; metformin; propolis; synergy.