Antithrombotic and antiplatelet activities of indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe)

Edible insects have been reported to produce metabolites showing various pharmacological activities, recently emerging as rich sources of health functional food and medicines. In particular, 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-beta-carboline-3-carboxylic acid (2), (1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (3), (3S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (4), and L-tryptophan (5) were isolated from the insect. Among them, compounds 1 and 2 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X 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.