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[micro]M 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 IC(50)
values of 6.25 and 15.76[micro]M. 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 26x 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.
Eur J Pharm Sci. 2012 May 17