Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 21, Issue 6, Pages 1217-1227Publisher
WILEY
DOI: 10.1111/jcmm.13055
Keywords
Protaetia brevitarsis seulensis (Kolbe); indole alkaloids; coagulation cascade; fibrinolysis
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Funding
- Agenda programme, Rural Development Administration [PJ010840]
- National Research Foundation of Korea [22A20154413076] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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--carboline-3-carboxylic acid (2), (1S,3S)-1-methyl-1,2,3,4-tetrahydro--carboline-3-carboxylic acid (3), (3S)-1,2,3,4-tetrahydro--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.
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