Abstract
Eight alkaloids recently isolated from the roots of Nauclea orientalis (L.) L. were obtained to evaluate the lipoxygenase (LOX) inhibitory activity. According to the LOX inhibitory assay, the cis isomer 1 (IC50 39.2±1.1 μM) was more potent than the trans isomer 2 (IC50 52.1±1.5 μM) (P < 0.05). Compound 5 (IC5057.8±1.8 μM) was more potent than 6 (IC50 97.6±3.4 μM), 3 (IC50 112.1±2.6 μM) and 4 (inactive) (P <0.05), respectively. Alkaloid glycosides 7 and 8 were completely inactive in a screening assay. All active indole alkaloids were inactive in DPPH and 13-HPOD scavenging assays at the concentration of 100 μM. Moreover, these compounds did not exhibit the interferential effects on the Fe2+/Fe3+ redox state as indicated by the iron reduction and oxidation assays. The enzyme kinetic study revealed that 1, 2 and 6 inhibited sb-LOX-1 through the mixed inhibition with a set of inhibition constants (K i and K' i ) of 9 and 22, 17 and 46, and 16 and 32 μM, respectively. Indole alkaloids 3 and 5 were the uncompetitive and noncompetitive inhibitors with the K i of 24 and 8 μM. These findings undoubtedly demonstrated that these active indole alkaloids were non-redox lipoxygenase inhibitors.