Activity-Guided Isolation of sn-1,3-Dipalmitoyl-2-oleoylglycerol as Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitor from Skipjack Tuna (Katsuwonus pelamis)

The skipjack tuna (Katsuwonus pelamis) is one of the least commercially exploited tuna globally. The possible medicinal benefits of K. pelamis extract have not been explored. We investigated the 70% ethanol (EtOH) soluble fractions of skipjack tuna heart for the inhibition of protein-tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The dichloromethane (CH2Cl2) fraction significantly inhibited the activities of PTP1B and α-glucosidase. Repeated column chromatography of the active CH2Cl2 fraction based on bioactivity-guided fractionation yielded cholesterol, cholesteryl myristate, and sn-1,3-dipalmitoyl-2-oleoylglycerol; the latter significantly inhibited PTP1B and α-glucosidase. Kinetic study revealed that sn-1,3-dipalmitoyl-2-oleoylglycerol showed mixed-type inhibition against PTP1B. Docking simulations showed that sn-1,3-dipalmitoyl-2-oleoylglycerol selectively inhibited PTP1B and α-glucosidase by targeting its active site and exhibited good binding affinity, with a docking score of −7.4 and −7.1 kcal/mol, respectively. Moreover, 70% EtOH, CH2Cl2 and EtOAc fractions, and sn-1,3-dipalmitoyl-2-oleoyl glycerol significantly inhibited ONOO−mediated albumin nitration. These results implicate tuna heart extract as a potential functional food ingredient for the prevention and treatment of diabetes and its associated complications.