Studies on Shokyo, Kanzo, and Keihi in Kakkonto Medicine on Prostaglandin E 2 Production in Lipopolysaccharide-Treated Human Gingival Fibroblasts

Abstract

We previously demonstrated that a kampo medicine, kakkonto, decreases lipopolysaccharide- (LPS-) induced prostaglandin E 2 (PGE 2 ) production by human gingival fibroblasts. In this study, we examined the herbs constituting kakkonto that exhibit this effect. Shokyo strongly and concentration dependently and kanzo and keihi moderately decreased LPS-induced PGE 2 production. Shokyo did not alter cyclooxygenase-2 (COX-2) activity, cytosolic phospholipase A 2 (cPLA 2 ), annexin 1 and COX-2 expression, and LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Kanzo inhibited COX-2 activity but increased annexin 1 and COX-2 expression and did not alter LPS-induced ERK phosphorylation. Keihi inhibited COX-2 activity and LPS-induced ERK phosphorylation but slightly increased COX-2 expression and did not alter cPLA 2 and annexin 1 expression. These results suggest that the mechanism of shokyo is through the inhibition of cPLA 2 activity, and that of kanzo and keihi is through the inhibition of COX-2 activity and indirect inhibition of cPLA 2 activity. Therefore, it is possible that shokyo and kakkonto are clinically useful for the improvement of inflammatory responses.