New phenolics from the leaves and twigs of Osteomeles schwerinae and their inhibitory effects on AGE formation and RLAR in vitro and vessel dilation in larval Zebrafish in vivo

In our continuing efforts to identify effective naturally sourced agents for diabetic complications, three new phenolic biphenyls (1-3), 5'-methoxy-(1,1'-biphenyl)-3,4,3'-triol (1), 5'-methoxy-(1,1'-biphenyl)-3,4,3'-triol 3'-O-β-D-glucopyranoside (2), and 3',5'-dimethoxy-(1,1'-biphenyl)-3,4-diol 3-O-β-D-glucopyranoside (3), and one new lignan glycoside, icariol A2 9′-O-α-L-rhamnopyranoside (4), were isolated from the leaves and twigs of Osteomeles schwerinae. The structures of the new compounds were established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds (1-4) on AGEs formation and RLAR in vitro were examined. Of the tested compounds, only phenolic biphenyls (1-3) markedly inhibited AGE formation with IC₅₀ values of 39.5 – 169.1 µM, compared with that of a positive control, aminoguanidine (IC₅₀= 975.9 µM). In the RLAR assay, consistent with the inhibition of AGE formation, phenolic biphenyls (1-3) exhibited considerable inhibition of RLAR with IC₅₀ values of 3.7 – 13.8 µM, compared with that of a positive control, 3,3-tetramethyleneglutaric acid (TMG, IC₅₀= 24.1 µM). In addition, the effects of these isolates on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish were also investigated. Of the tested compounds, only compound 1 significantly reduced the dilation of HG-induced hyaloid-retinal vessels. This compound reduced the diameters of HG-induced hyaloid-retinal vessels by about 95% and 99% at 10 and 20 µM, respectively, versus the HG-treated control group, whereas the positive control, VEGFR inhibitor, exhibited 77% inhibition at a concentration of 1 µM.