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 thiocarbamates, N ‐benzyl carbamates, benzyl nitriles, and a benzyl ester. Among these, methyl 2‐[4‐( α ‐ L ‐rhamnopyranosyl)phenyl]acetate ( 2 ), N ‐[4‐( β ‐ L ‐rhamnopyranosyl)benzyl]‐1‐ O ‐ α ‐ D ‐glucopyranosylthiocarboxamide ( 3 ), 1‐ O ‐phenyl‐ α ‐ L ‐rhamnopyranoside ( 5 ), and 4‐[( β ‐ D ‐glucopyranosyl)‐(1→3)‐( α ‐ 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‐( α ‐ L ‐rhamnopyranosyl)phenylacetonitrile; 1 ), niazicin A (=methyl N ‐{4‐[(4′‐ O ‐acetyl‐ α ‐ L ‐rhamnopyranosyl)benzyl]}thiocarbamate; 4 ), methyl N ‐{4‐[( α ‐ L ‐rhamnopyranosyl)benzyl]}carbamate ( 7 ), and methyl N ‐{4‐[(4′‐ O ‐acetyl‐ α ‐ L ‐rhamnopyranosyl)benzyl]}carbamate ( 8 ). The combined yield of these compounds from dried M. oleifera fruits was 1.63%. In rodent pancreatic β ‐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.