ABSTRACT
Isolated oligostilbenes from G. macrostachyum exhibited sbLOX-1 inhibitory activity with IC50 values ranging from 0.14-11.91 microM. Of these oligostilbenoids, 12 (IC50 0.14 +/- 0.01 microM), 10 (IC50 0.33 +/- 0.11 microM), 11 (IC50 0.49 +/- 0.05 microM) and 7 (IC50 1.03 +/- 0.43 microM) 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 Ki values of 11.2 and 71.4 nM. Compound 10 inhibited sbLOX-1 through mixed-competitive mechanisms (Ki = 13.8 nM and Ki' 56.7 nM). Moreover, 12 was an uncompetitive inhibitor with a Ki 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 Fe(3+)-bound sbLOX-1 model, as indicated by UV spectrophotometric and CD spectroscopic studies.
Subject(s)
Gnetum/chemistry , Lipoxygenase Inhibitors/chemistry , Lipoxygenase Inhibitors/pharmacology , Lipoxygenase/metabolism , Stilbenes/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Biphenyl Compounds/chemistry , Hydrogen Peroxide , Iron/chemistry , Oxidation-Reduction , Picrates/chemistry , Stilbenes/chemistryABSTRACT
Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. The phytochemical investigation of stilbenoids from Gnetum macrostachyum Hook. f. led to the isolation of trans-resveratrol (1), isorhapotigenin (2), gnetol (3), bisisorhapontigenin B (4), gnetin C (5), parvifolol A (6), latifolol (7) and gnetuhainin C (8). The isolated stilbenoids were evaluated for in vitro antiplatelet activities via agonist-induced platelet aggregation and static platelet-collagen adhesion assays using washed human platelets. Compounds 1, 2 and 3 were active in the inhibition of arachidonic acid (AA)-induced platelet aggregation. Compound 2 and its dimer, compound 4, were the most active stilbenoids in thrombin-induced platelet aggregation. Moreover, compounds 4, 5 and 6, tended to be more potent than monomeric and trimeric stilbenoids in a human platelet-collagen adhesion assay under static conditions. This is the first report of the antiplatelet activity of stilbenoids isolated from G. macrostachyum.
Subject(s)
Gnetum/chemistry , Platelet Adhesiveness/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Stilbenes/pharmacology , Arachidonic Acid/pharmacology , Humans , Inhibitory Concentration 50 , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Platelet Aggregation Inhibitors/isolation & purification , Stilbenes/isolation & purificationABSTRACT
Four new oligostilbenes, macrostachyols A-D (1-4) along with six known stilbenoids (5-10), were isolated from the roots of Gnetum macrostachyum. These compounds were also evaluated for their cytotoxicity towards HeLa and KB cell lines. Only compound 4 showed the significant cytotoxicity to HeLa cells with IC(50) value of 4.13 µM.
