Rutaecarpine, a quinazolinocarboline alkaloid, inhibits prostaglandin production in RAW264.7 macrophages

In order to delineate the mechanism involved in the anti-inflammatory activ ity of rutaecarpine, its effects on the production of prostaglandin (PG) an d therein involved enzymes were examined. Rutaecarpine reduced the producti on of PGE(2) in RAW264.7 cells treated with lipopolysaccharide (LPS) in a d ose dependent manner when added to the culture media at the time of stimula tion. However, the inhibition of total cellular cyclooxygenase (COX) activi ty under the same experimental condition was observed only at high concentr ations of rutaecarpine. Rutaecarpine did not affected the levels of COX-2 m RNA and protein in macrophages stimulated with UPS. Calcium ionophore A2318 7 induced-PG production and [H-3]-arachidonic acid release were significant ly decreased by the pretreatment of rutaecarpine for 30 minutes. With the s ame treatment schedule, however, rutaecarpine failed to alter the activitie s of cellular COX-1 and COX-2. Collectively, our data suggest that anti-inf lammatory effect of rutaecarpine is, at least in part, ascribed to the dimi nution of PG production through inhibition of arachidonic acid release albe it the nature of its effects on PLA(2) activity remains to be elaborated.