Flavonoids from plant origin show anti-inflammatory activity in vitro and in vivo. In addition to inhibition of
inflammation-associated
enzymes, such as
cyclooxygenases (COX) and
lipoxygenases, they have been found to regulate the expression of
inflammation-associated
proteins from in vitro experiments. In order to prove in vivo behavior and the potential for beneficial use against inflammatory skin disorders, the effect of
wogonin (5,7-dihydroxy-8-methoxyflavone) on in vivo expression of several
inflammation-associated genes was examined in the intact as well as in the inflamed mouse skin by
reverse transcriptase-polymerase chain reaction analysis. When applied topically on the intact skin, only a high dose treatment of
wogonin (1000 microg/ear/3 days) slightly increased COX-1 and
fibronectin mRNA. On the other hand,
wogonin at the doses of 250-1000 microg/ear/3 days potently lowered
mRNA levels of COX-2 and
tumor necrosis factor-alpha with less effect on
intercellular adhesion molecule-1 and
interleukin-1beta in a sub-chronic skin
inflammation model of tetradecanoylphorbol-13-acetate-induced ear
edema (multiple treatment). The decrease of
prostaglandin E(2) concentration (27.3-34.3%) was concomitantly observed in the
wogonin-treated groups. A similar effect was also observed in an acute
inflammation model of
arachidonic acid-induced ear
edema. From the present study,
wogonin was proved to differentially regulate the expression of
inflammation-associated genes in vivo and to become a useful therapeutic agent for skin inflammatory diseases mainly due to its modulation of the expression of proinflammatory molecules.