Comparison of metabolism and biological properties among positional isomers of quercetin glucuronide in LPS- and RANKL-challenged RAW264.7 cells

The major quercetin metabolite, quercetin-3-glucuronide, exerts various biological activities, including anti-inflammatory effects. This study aimed to evaluate the metabolic profiles and biological properties of the positional isomers of quercetin monoglucuronides (Q3G, Q7G, Q3'G, and Q4'G) in activated macrophages. In addition to quercetin aglycone, Q7G was more cytotoxic than the other quercetin monoglucuronides (QGs), which corresponded to its lower stability under neutral pH conditions. Q3G was most effective in inhibiting both LPS-dependent induction of IL-6 and RANKL-dependent activation of tartrate-resistant acid phosphatase; however, Q3'G and Q4'G may also help exert biological activities without potential cytotoxicity. The deconjugation efficacy to generate quercetin aglycone differed among QGs, with the highest efficacy in Q3G. These results suggest that the chemical or biological properties and metabolic profiles may depend on the stability of QGs to generate quercetin aglycone using beta-glucuronidase.

Automated summary

This study evaluated the metabolic and biological properties of different positional isomers of quercetin monoglucuronides in activated macrophages. The results showed that these isomers have the potential to exert anti-inflammatory effects, with Q3G being the most effective in inhibiting inflammation. Q7G was found to be more cytotoxic due to its lower stability under neutral pH conditions. Different isomers also varied in their ability to generate quercetin aglycone, with Q3G having the highest efficacy.