Anti-inflammatory, Radical-Scavenging, and Chelating Activities of Nor-Triterpenes from Galphimia Species

Anti-inflammatory and radical-scavenging activities of the methanolic extract from the leaves of Galphimia spp. collected in Morelos, Mexico, and isolated galphimidin and galphimidin B, were evaluated. Nor-triterpenes galphimidin and galphimidin B displayed anti-inflammatory activity inhibiting the nitric oxide production by the lipopolysaccharide-induced RAW 264.7 cell model, with IC₅₀ values of 22.62 and 20.19 μg/ml, respectively, which were higher than the crude extract with an IC₅₀ of 42.92 µg/ml. Furthermore, the 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice assay displayed results of EC₅₀ of 2.03 mg/ear to the methanolic extract, 1.91 mg/ear to galphimidin, and 1.42 mg/ear to galphimidin B. Docking analysis of galphimidin and galphimidin B at the iNOS active site indicated the negative influence of water molecules by mediating the ligand–protein interaction through hydrogen bond interactions that increase the energy expenditure. These results explain the observed anti-inflammatory action of galphimidin and galphimidin B by iNOS inhibition, which is better modulated in silico by the absence of water in the active site. The methanolic extract showed a low radical-scavenging activity inhibiting free radicals DPPH^• with values of 57.33% compared to isoquercetin and rutin, as positive controls. Nevertheless, the crude extract displayed high activity inhibiting ABTS^•+ free radicals at 83.31% that was in accordance with high reducing potential of total polyphenols by the Folin-Ciocalteu method with value of 3591.11 mg of gallic acid/g of biomass. Galphimidin and galphimidin B did not present radical-scavenging activities but showed metal-chelating activity of 27.62 and 30.54%, which were higher values than ethylenediaminetetraacetic acid, as positive control.