Inhibitory Activities of Natural Products on Lipopolysaccharide Induced Prostaglandin Production in Mouse Macrophages

Abstract

Two isoforms of cyclooxygenase (COX) have been identified - COX-1, which is constitutively expressed in most tissues, and the inducible form, COX-2, of which expression is induced by inflammatory signals and mitogens. It has been considered that the benificial effects of NSAIDs are due to the inhibition of COX-2 activity and the side effects are from the inhibition of COX-1 activity. There-fore, it is essential to develop selective COX-2 inhibitor for developing new GI-tolerable NSAIDs. To discover new leads for developing selective COX-2 inhibitors, three-hundred extracts of natural pro-ducts were primarily screened with the system of prostaglandin accumulation in LPS-stimulated mouse peritoneal macrophages. To identify whether these inhibitory activities of crude extracts on the accumulation of prostaglandins were derived from direct action against COX-2, the effects of selected extracts on exogenous arachidonic acid-derived production of prostaglandin by LPS-stimulated macrophages were determined. Among them, 5 methanol extracts of natural products, such as Zingiberis Rhizoma, Alpinae Officinarum Rhizoma, Caryophilli Flos, Scutellariae Radix, Dalbergia ordorifera, inhibited more than 70% of the prostaglandin production in LPS-stimulated mouse peritoneal macrophages at a concentration of 1 μg/ml.