Effects of rhinacanthins from Rhinacanthus nasutus on nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha releases using RAW264.7 macrophage cells.

Three naphthoquinone derivatives, rhinacanthin-C (1), -D (2) and -N (3) were isolated from the leaves of Rhinacanthus nasutus extract and were tested for anti-inflammatory activity. The result indicated that all three compounds possessed very potent anti-inflammatory activity against lipopolysaccharide (LPS)-induced nitric oxide release with IC(50) values of 1.8, 6.2 and 3.0 microM, respectively. In addition, the effects of rhinacanthin-C, -D and -N on LPS induced release of prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF-alpha) were also examined. It was found that rhinacanthin-C exhibited the most potent on PGE(2) release with an IC(50) value of 10.4 microM, followed by rhinacanthin-D (IC(50)=14.4 microM) and rhinacanthin-N (IC(50)=52.1 microM), whereas those for TNF-alpha were inactive (IC(50)>100 microM). The mechanisms in transcriptional level of rhinacanthin-C were found to inhibit iNOS and COX-2 gene expressions in LPS-induced NO and PGE(2) releases from RAW264.7 cells in concentration-dependent manners. Regarding active constituents for anti-inflammatory activity of R. nasutus, rhinacanthins are responsible for this effect through the inhibition of NO and PGE(2) releases. The finding may support the traditional use of R. nasutus leaves for treatment of the inflammatory-related diseases.