title: Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe).
abstract: 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.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: JungIn
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu, Republic of Korea.|Department of Agricultural Biology, The National Academy of Agricultural Science, RDA, Wanju-gun, Republic of Korea.
authors.forename: Mi-Ae
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biology, The National Academy of Agricultural Science, RDA, Wanju-gun, Republic of Korea.
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001517:Coleoptera / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007313:Insecta / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects*; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D026121:Indole Alkaloids
keywords: Protaetia brevitarsis seulensis (Kolbe); coagulation cascade; fibrinolysis; indole alkaloids