BACKGROUND: Quercetin is a natural flavonoid, which widely exists in nature, such as tea, coffee, apples, and onions. Numerous studies have showed that quercetin has multiple biological activities such as anti-oxidation, anti-inflammatory, and anti-aging. Hence, quercetin has a significant therapeutic effect on cancers, obesity, diabetes, and other diseases. In the past decades, a large number of studies have shown that quercetin combined with other agents can significantly improve the overall therapeutic effect, compared to single use. PURPOSE: This work reviews the pharmacological activities of quercetin and its derivatives. In addition, this work also summarizes both in vivo and in vitro experimental evidence for the synergistic effect of quercetin against cancers and metabolic diseases. METHODS: An extensive systematic search for pharmacological activities and synergistic effect of quercetin was performed considering all the relevant literatures published until August 2021 through the databases including NCBI PubMed, Scopus, Web of Science, and Google Scholar. The relevant literatures were extracted from the databases with following keyword combinations: "pharmacological activities" OR "biological activities" OR "synergistic effect" OR "combined" OR "combination" AND "quercetin" as well as free-text words. RESULTS: Quercetin and its derivatives possess multiple pharmacological activities including anti-cancer, anti-oxidant, anti-inflammatory, anti-cardiovascular, anti-aging, and neuroprotective activities. In addition, the synergistic effect of quercetin with small molecule agents against cancers and metabolic diseases has also been confirmed. CONCLUSION: Quercetin cooperates with agents to improve the therapeutic effect by regulating signal molecules and blocking cell cycle. Synergistic therapy can reduce the dose of agents and avoid the possible toxic and side effects in the treatment process. Although quercetin treatment has some potential side effects, it is safe under the expected use conditions. Hence, quercetin has application value and potential strength as a clinical drug. Furthermore, quercetin, as the main effective therapeutic ingredient in traditional Chinese medicine, may effectively treat and prevent coronavirus disease 2019 (COVID-19).

College of Food Science and Engineering Jilin University Changchun 130062 China

Department of Pharmacology and Toxicology Faculty of Pharmacy Charles University Heyrovskeho 1203 Hradec Kralove CZ500 05 Czech Republic

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