Highly Potent Oligostilbene sbLOX-1 Inhibitor from Gnetum macrostachyum

Abstract

Isolated oligostilbenes from G. macrostachyum exhibited sbLOX-1 inhibitory activity with IC₅₀ values ranging from 0.14–11.91 μM. Of these oligostilbenoids, 12 (IC0 0.14±0.01 μM), 10 (IC0 0.33±0.11 μM), 11 (IC₅₀ 0.49±0.05 μM) and 7 (IC₅₀ 1.03 ± 0.43 μM) were more active than nordihydroguaiaretic acid (NDGA) (P < 0.05) which was the positive control. The enzyme kinetic analysis revealed that 7 and 11 inhibited sbLOX-1 noncompetitively with K _i values of 11.2 and 71.4 nM. Compound 10 inhibited sbLOX-1 through mixed-competitive mechanisms (K _i = 13.8 nM and K^' _i 56.7 nM). Moreover, 12 was an uncompetitive inhibitor with a K _i value of 0.8 nM. The inhibitory activity of oligostilbenes did not result from the antioxidant property, as demonstrated by DPPH and 13-HPOD scavenging assays. These compounds also showed ferric reducing capabilities, but had no effect in a Fe³⁺-bound sbLOX-1 model, as indicated by UV spectrophotometric and CD spectroscopic studies.