Anti-inflammatory activity and percutaneous absorption of quercetin and its polymethoxylated compound and glycosides: The relationships to chemical structures

The potential of quercetin-related compounds for topical application has not previously been systematically investigated. To better elucidate relationships of the structure and activity with skin permeation, some quercetin compounds were used as permeants, including aglycone, a polymethoxylated compound (quercetin 3,5,7,3′,4′-pentamethylether, QM), and seven glycosides. Quercetin and the glycoside with glucopyranuronic acid (Q4) at a dose of 30 μM completely inhibited superoxide anion activated neutrophils. QM also potentially suppressed superoxide by 90%. Both quercetin and QM showed inhibitory activity on elastase release with respective IC₅₀ values of 6.25 and 15.76 μM. Glycosylation significantly diminished this activity. Both an infinite concentration and saturated solubility in pH 7 buffer were used as permeant doses for the in vitro permeation experiments. The flux or permeability coefficient, which is the indicator for total absorption of dermal delivery due to the use of nude mouse skin, was the greatest for QM, followed by the glycosides and quercetin. QM showed 26× greater flux compared to quercetin. No penetration of quercetin occurred at the dose of saturated solubility. Rutin generally exhibited the highest skin permeation among the glycosides. It was found that the glycoside enantiomers (Q2 and Q3) revealed completely different permeation profiles. The stratum corneum was the principal penetration barrier for quercetin and its glycosides but not QM. Rutin provoked some skin redness and inflammation after a 5-day administration in nude mouse. QM caused no irritation, suggesting that it is a superior candidate for topical delivery.