Insulin secretagogues from Moringa oleifera with cyclooxygenase enzyme and lipid peroxidation inhibitory activities

Bioassay-directed isolation and purification of the methanol extract of Moringa oleifera fruits yielded bioactive N-benzyl thiocarbarnates, N-benzyl carbarnates, benzyl nitriles, and a benzyl ester. Among these, methyl 2-[4-(alpha-L-rhamnopyranosyl)phenyl] acetate (2), N-[4-(beta-L-rhamnopyranosyl)benzyl]-1-O-alpha-D-glucopyranosylthiocarboxamide (3), 1-O-phenyl-alpha-L-rhamnopyranoside (5), and 4-[(beta-D-glucopyranosyl)-(1 --> 3)-(alpha-L-rhamnopyranosyl)]phenylacetonitrile (6) are novel, and their structures were determined by spectroscopic methods. The known compounds isolated and characterized from the MeOH extract were niazirin (=4-(alpha-L-rhamnopyranosyl)phenylacetonitrile; 1), niazicin A (=methyl N-{4-[(4'-O-acetyl-alpha-L-rhamnopyranosyl)benzyl]})thiocarbamate; 4), methyl N-{4-[(alpha-L-rhamnopyranosyl)benzyl]}carbamate (7), and methyl N-[4-[(4'-O-acetyl-alpha-L-rhamnopyranosyl)benzyl]}carbamate (8). The combined yield of these compounds from dried M. oleifera fruits was 1.63%. In rodent pancreatic beta-cells (INS-1), compounds 4, 5, 6, 7, and 8 at 100 ppm significantly stimulated insulin release. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibition assays revealed that 5 and 6 were most active at 83 ppm. Compound 6, however, demonstrated greater specificity for inhibition of COX-2 enzyme (46%) than COX-1 enzyme. Lipid peroxidation assays revealed that 4 and 6 at 50 ppm inhibited peroxidation reactions by 80 and 95%, respectively, while 3 and 8 inhibited lipid peroxidation by 35%. These compounds did not inhibit the cell growth when tested with human breast (MCF-7), central nervous system (CNS, SF-268), lung (NCI-H460), or colon (HCT-116) cancer cell lines. Moreover, these compounds were not cytotoxic at the concentrations tested.