Isolation and identification of phenolic compounds from the seeds of Perilla frutescens (L.) and their inhibitory activities against α-glucosidase and aldose reductase

Five phenolic compounds were isolated from the seeds of Perilla (Perilla frutescens L.) using gradient solvent fractionation, silica gel column chromatography, and preparative high-performance liquid chromatography (HPLC). Their chemical structures were identified as caffeic acid-3-O-glucoside (1), rosmarinic acid-3-O-glucoside (2), rosmarinic acid (3), luteolin (4), and apigenin (5) using NMR spectroscopy and HPLC–ESI/MS analysis. Among them, luteolin (4) inhibited α-glucosidase (EC 3.2.1.20) with IC50 value of 45.4 μM. The inhibition kinetic analysed by Dixon plot indicate that luteolin is a noncompetitive inhibitor, and the inhibition constant KI was calculated at 45.0 μM. Moreover, rosmarinic acid (3) and luteolin (4) inhibited recombinant human aldose reductase (EC 1.1.1.21) with IC50 values of 11.2 and 0.6 μM, respectively. Notably, the inhibition kinetic of luteolin (4) follows a hyperbolic dependence on aldose reductase inhibition by Dixon plot. Thus, inhibition kinetic indicates that luteolin (4) is a mixed-type inhibitor.