Furanocoumarins from Kaffir lime and their inhibitory effects on inflammatory mediator production

Two known furanocoumarins, namely, 6',7'-dihydroxybergamottin (1) and oxypeucedanin hydrate (2), were isolated from Kaffir lime (Citrus hystrix DC) fruit peel using an assay of nitric oxide scavenging effect-guided fractionation. The inhibitory activities of isolated coumarins on the production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were studied in mouse macrophages RAW264.7 cells, whereas their inhibitory effect on cyclooxygenase-2 (COX-2) production was investigated using HT-29 and HCT116 cells. The results demonstrated that 1 inhibited lipopolysaccharide-interferon gamma-induced NO and iNOS production in RAW264.7 cells and COX-2 production in HT-29 and HCT116 cells with IC50 values of 16.16 +/- 1.08, 18.63 +/- 1.42, 18.19 +/- 0.95 and 17.53 +/- 0.88 mu g/mL, respectively; 2 showed IC50 values of 18.23 +/- 1.25, 22.54 +/- 1.56, 22.27 +/- 1.14 and 23.24 +/- 1.05 mu g/mL, respectively. Additionally, the positive control curcumin exhibited these activities with IC50 values of 12.52 +/- 0.63, 15.55 +/- 1.34, 14.29 +/- 0.58 and 16.14 +/- 0.65 mu g/mL, respectively. The inhibitory effect of 1 on the production of iNOS and COX-2 was significantly stronger than that of 2. This study indicated that furanocoumarins from Kaffir lime fruit peels have potency for further development as an anti-inflammatory drug.