Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe)

Protaetia brevitarsis seulensis (Kolbe) has been temporarily registered as a food material by the Ministry of Food and Drug Safety of Korea (MFDS). The current study aimed to discover small antithrombotic molecules from this edible insect. Five indole alkaloids, 5‐hydroxyindolin‐2‐one (1), (1R,3S)‐1‐methyl‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylic acid (2), (1S,3S)‐1‐methyl‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylic acid (3), (3S)‐1,2,3,4‐tetrahydro‐β‐carboline‐3‐carboxylic acid (4) and L‐tryptophan (5), were isolated from the insect. Among them, compounds 1 and 2 prolonged aPTT and PT and impaired thrombin and FXa generation on HUVEC surface. Moreover, these compounds inhibited platelet aggregation. Antithrombotic effects of compounds 1 and 2 were further confirmed in pre‐clinical models of pulmonary embolism and arterial thrombosis. Collectively, these results demonstrated that compounds 1 and 2 could be effective antithrombotic agents and serve as new scaffolds for the development of antithrombotic drug.