The objective of this work was to investigate the antidiabetic, antiglycation, and antioxidant potentials of ethanolic extract of seeds of Brazilian Passiflora edulis fruits (PESE), a major by-product of the juice industry, and piceatannol (PIC), one of the main phytochemicals of PESE. PESE, PIC, and acarbose (ACB) exhibited IC50 for alpha-amylase, 32.1 ± 2.7, 85.4 ± 0.7, and 0.4 ± 0.1 µg/mL, respectively, and IC50 for alpha-glucosidase, 76.2 ± 1.9, 20.4 ± 7.6, and 252 ± 4.5 µg/mL, respectively. The IC50 of PESE, PIC, and sitagliptin (STG) for dipeptidyl-peptidase-4 (DPP-4) was 71.1 ± 2.6, 1137 ± 120, and 0.005 ± 0.001 µg/mL, respectively. PESE and PIC inhibited the formation of advanced glycation end-products (AGE) with IC50 of 366 ± 1.9 and 360 ± 9.1 µg/mL for the initial stage and 51.5 ± 1.4 and 67.4 ± 4.6 µg/mL for the intermediate stage of glycation, respectively. Additionally, PESE and PIC inhibited the formation of β-amyloid fibrils in vitro up to 100%. IC50 values for 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) scavenging activity of PESE and PIC were 20.4 ± 2.1, and 6.3 ± 1.3 µg/mL, respectively. IC50 values for scavenging hypochlorous acid (HOCl) were similar in PESE, PIC, and quercetin (QCT) with values of 1.7 ± 0.3, 1.2 ± 0.5, and 1.9 ± 0.3 µg/mL, respectively. PESE had no cytotoxicity to the human normal bronchial epithelial (BEAS-2B), and alpha mouse liver (AML-12) cells up to 100 and 50 µg/mL, respectively. However, 10 µg/mL of the extract was cytotoxic to non-malignant breast epithelial cells (MCF-10A). PESE and PIC were found to be capable of protecting cultured human cells from the oxidative stress caused by the carcinogen NNKOAc at 100 µM. The in vitro evidence of the inhibition of alpha-amylase, alpha-glucosidase, and DPP-4 enzymes as well as antioxidant and antiglycation activities, warrants further investigation of the antidiabetic potential of P. edulis seeds and PIC.
