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Inhibitory effect of ethanol extract of Gryllus bimaculatus on platelet aggregation and glycoprotein IIb/IIIa activation

쌍별귀뚜라미 에탄올 추출물의 혈소판응집반응과 당단백질 IIb/IIIa 활성화 억제 효과

  • Hyuk-Woo Kwon (Department of Biomedical Laboratory Science, Far East University) ;
  • Man Hee Rhee (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Jung-Hae Shin (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2023.04.19
  • Accepted : 2023.05.22
  • Published : 2023.12.31

Abstract

Platelets act a fundamental role in primary- and secondary-hemostasis, however, platelet activation may cause thrombosis simultaneously. Therefore, control of platelet aggregation is crucial in preventing thrombosis-mediated diseases. Recently, the development of insect materials is attracting attention. Among the highly nutritious functional food sources, insects such as two-spotted cricket (Gryllus bimaculatus). Gryllus bimaculatus (G. bimaculatus) contains high protein and unsaturated fatty acids and has been registered as a food material September 2015 by the Ministry of Food and Drug Safety of Korea. In this study, we examined whether G. bimaculatus extract (GBE) inhibits platelet aggregation, intracellular calcium mobilization, thromboxane A2 production and glycoprotein IIb/IIIa (integrin αIIb/β3) activation. We investigated whether GBE can regulate signaling molecules, such as 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A2, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β, and SYK. Taken together, GBE is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

혈소판은 1차 및 2차 지혈에서 근본적인 역할을 하는 세포지만 혈소판의 과도한 활성화는 혈전증을 유발할 수 있다. 따라서 혈소판 응집의 적절한 조절은 혈전증 매개 질환을 예방하는 데 중요하다. 최근 곤충소재의 개발이 주목을 받고 있다. 다양한 곤충 자원 중 고영양 기능성 식품원으로는 쌍별귀뚜라미(Gryllus bimaculatus)와 같은 곤충류가 있다. 쌍별귀뚜라미 는 고단백 및 불포화지방산을 함유하고 있으며 2015년 9월 식품의약품안전처로부터 식품원료로 등록되었다. 본 연구에서는 쌍별귀뚜라미 에탄올 추출물(G. bimaculatus extract)이 혈소판 응집, 세포 내 Ca2+ 조절, thromboxane A2 생산 및 glycoprotein IIb/IIIa (integrin αIIb/β3) 활성화를 억제하는지 여부를 확인하고. 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A2, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β 및 SYK 같은 신호 분자를 조절할 수 있는지 여부를 조사했다. 우리는 쌍별귀뚜라미 추출물이 혈소판 관련 혈전증 및 심혈관 질환을 예방할 수 있는 잠재적인 치료 약물로 가치가 있음을 규명하였다.

Keywords

Acknowledgement

이 논문은 2020년도 정부(교육부)의 재원으로 한국연구재단의 지원을 받아 수행된 기초연구사업임(No. 2020R1I1A1A01067709).

References

  1. Ruggeri ZM, Mendolicchio GL (2007) Adhesion mechanisms in platelet function. Circ Res 100: 1673-1685. doi: 10.1161/01.RES.0000267878.97021.ab
  2. Jennings LK (2009) Role of platelets in atherothrombosis. Am J Card 103: 4A-10A. doi: 10.1016/j.amjcard.2008.11.017
  3. Barnathan ES, Schwartz JS, Taylor LT, Laskey WK, Kleaveland JP, Kussmaul WG, Hirshfeld Jr JW (1987) Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty. Circulation 76: 125-134. doi: 10.1161/01.CIR.76.1.125
  4. Jackson SP (2011) Arterial thrombosis-insidious, unpredictable and deadly. Nat Med 17: 1423-1436. doi: 10.1038/nm.2515
  5. Kim SY, Kim DI, Koo HY, Kim JE, Kim HJ, Lee YB, Kim YC (2020) Storage conditions and oviposition methods for Gryllus bimaculatus (Gryllidae) eggs. Korean J Appl Entomol 59: 133-138. doi: 10.5656/KSAE.2020.05.0.018
  6. Kim SH, Kim YK, Han JS (2020) Antioxidant Activities and Nutritional Components of Cricket (Gryllus bimaculatus) Powder and Protein Extract. Asian J Beauty Cosmetol 18: 163-172. doi: 10.20402/ajbc.2020.0016
  7. Park B, Kim SY, Kim YN, Yang SD, Seo WG, Han SY, Yoo YC (2022) Inhibitory Effect of Hot-Water Extract of Gryllus bimaculatus on Inflammatory Responses and NLRP3 Inflammasome Activation in Macrophages. J Korean Soc Food Sci Nutr 51: 115-124. doi: 10.3746/jkfn.2022.51.2.115
  8. Cho HT, Sim KS, Kim Y, Chang MH, Kim T, Lee SH, Kim JH (2019) Anti-diabetic activity of edible insect Gryllus bimaculatus extracts in insulin-deficient diabetic mice. J Korean Soc Food Sci Nutr 48: 165-1171. doi: 10.3746/jkfn.2019.48.10.1165
  9. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450. doi: 10.1016/S0021-9258(19)83641-4
  10. Varga-Szabo D, Braun A, Nieswandt B (2009) Calcium signaling in platelets. J Thromb Haemost 7: 1057-1066. doi: 10.1111/j.1538-7836.2009.03455.x
  11. Varga-Szabo D, Braun A, Kleinschnitz C, Bender M, Pleines I, Pham M, Nieswandt B (2008) The calcium sensor STIM1 is an essential mediator of arterial thrombosis and ischemic brain infarction. J Exp Med 205: 1583-1591. doi: 10.1084/jem.20080302
  12. Quinton TM, Dean WL (1992) Cyclic AMP-dependent phosphorylation of the inositol-1, 4, 5-trisphosphate receptor inhibits Ca2+ release from platelet membranes. Biochem Biophys Res Commun 184: 893-899. doi: 10.1016/0006-291X(92)90675-B
  13. Rosado JA, Sage SO (2001) Role of the ERK pathway in the activation of store-mediated calcium entry in human platelets. J Biol Chem 276: 15659-15665. doi: 10.1074/jbc.M009218200
  14. Kramer RM, Roberts EF, Um SL, Borsch-Haubold AG, Watson SP, Fisher MJ, Jakubowski JA (1996) p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase A2 (cPLA2) in thrombin-stimulated platelets evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2. J Biol Chem 271: 27723-27729. doi: 10.1074/jbc.271.44.27723
  15. McNicol A, Shibou TS (1998) Translocation and phosphorylation of cytosolic phospholipase A2 in activated platelets. Thromb Res 92: 19-26. doi: 10.1016/S0049-3848(98)00097-8
  16. Payrastre B, Missy K, Trumel C, Bodin S, Plantavid M, Chap H (2000) The integrin αIIb/β3 in human platelet signal transduction. Biochem Pharmacol 60: 1069-1074. doi: 10.1016/S0006-2952(00)00417-2
  17. Valet C, Severin S, Chicanne G, Laurent PA, Gaits-Iacovoni F, Gratacap MP, Payrastre B (2016) The role of class I, II and III PI 3-kinases in platelet production and activation and their implication in thrombosis. Adv Biol Regul 61: 33-41. doi: 10.1016/j.jbior.2015.11.008
  18. Chen J, De S, Damron DS, Chen WS, Hay N, Byzova TV (2004) Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice. Blood 104: 1703-1710. doi: 10.1182/blood-2003-10-3428
  19. Moore SF, Agbani EO, Wersall A, Poole AW, Williams CM, Zhao X, Hers I (2021) Opposing Roles of GSK3α and GSK3β Phosphorylation in Platelet Function and Thrombosis. Int J Mol Sci 22: 10656. doi: 10.3390/ijms221910656
  20. Yanaga F, Poole A, Asselin J, Blake R, Schieven GL, Clark EA, Watson SP (1995) Syk interacts with tyrosine-phosphorylated proteins in human platelets activated by collagen and cross-linking of the Fc γ-IIA receptor. Biochem J 311: 471-478. doi: 10.1042/bj3110471
  21. Obergfell A, Eto K, Mocsai A, Buensuceso C, Moores SL, Brugge JS, Shattil SJ (2002) Coordinate interactions of Csk, Src, and Syk kinases with αIIbβ3 initiate integrin signaling to the cytoskeleton. J Cell Biol 157: 265-275. doi: 10.1083/jcb.200112113
  22. Sudo T, Ito H, Kimura Y (2003) Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 4: 381-390. doi: 10.1080/09537100310001598819
  23. Schwarz UR, Walter U, Eigenthaler M (2001) Taming platelets with cyclic nucleotides. Biochem Pharmacol 62: 1153-1161. doi: 10.1016/S0006-2952(01)00760-2
  24. Udomsil N, Imsoonthornruksa S, Gosalawit C, Ketudat-Cairns M (2019) Nutritional values and functional properties of house cricket (Acheta domesticus) and field cricket (Gryllus bimaculatus). Food Sci Technol Res 25: 597-605. doi: 10.3136/fstr.25.597
  25. Larson MK, Shearer GC, Ashmore JH, Anderson-Daniels JM, Graslie EL, Tholen JT, Harris WS (2011) Omega-3 fatty acids modulate collagen signaling in human platelets. Prostaglandins Leukot Essent Fat Acids 84: 93-98. doi: 10.1016/j.plefa.2010.11.004
  26. Lee J, Lee W, Kim MA, Hwang JS, Na M, Bae JS (2017) Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe). J Cell Mol Med 21: 1217-1227. doi: 10.1111/jcmm.13055
  27. Kwon HW, Kim SD, Rhee MH, Shin JH (2022) Pharmacological Actions of 5-Hydroxyindolin-2 on Modulation of Platelet Functions and Thrombus Formation via Thromboxane A2 Inhibition and cAMP Production. Int J Mol Sci 23: 14545. doi: 10.3390/ijms232314545