[논문]콜라겐 유도의 혈소판에서 사이클릭 뉴클레오티드의 조절을 통한 Euchrestaflavone B의 혈전 형성 억제 효과

권혁우

doi:10.22889/kjp.2020.51.4.231

콜라겐 유도의 혈소판에서 사이클릭 뉴클레오티드의 조절을 통한 Euchrestaflavone B의 혈전 형성 억제 효과
Inhibitory Effects of Euchrestaflavone B on Thrombus Formation via Regulation of Cyclic Nucleotides in Collagen-induced Platelets 원문보기

생약학회지, v.51 no.4, 2020년, pp.231 - 237

권혁우 (극동대학교 임상병리학과)

Abstract ▼ AI-Helper

Euchrestaflavanone B (EFB) is a flavonoid that can be found in root bark, particularly in Cudrania tricuspidata (C. tricuspidata). The extract of C. tricuspidata is widespread throughout Asia and used in traditional medicine. In a previous study, we found anti-platelet effects of substances isolated from C. tricuspidata on collagen-induced human platelets. However, the C. tricuspidata still contains numerous substances, thus, we have searched new candidate, EFB isolated from C. tricuspidata for anti-platelet effect. Our results showed that EFA inhibited collagen-induced platelet aggregation and glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production and clot retraction. These results suggest that EFA has inhibitory effects on human platelet activities and thrombus formation and has potential value as a natural substance for preventing platelet-induced thrombosis.

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표/그림 (6)

그림 Fig. 1. Chemical structure of euchrestaflavanone B.
그림 Fig. 2. Effects of euchrestaflavanone B on platelet aggregation and cytotoxicity. (A) Effect of euchrestaflavanone B on collagen-induced human platelet aggregation. (B) Half maximal inhibitory concentration (IC₅₀) value of euchrestaflavanone B in collagen-induced human platelet aggregation. (C) Effect of euchrestaflavanone B on cytotoxicity. Platelet aggregation and cytotoxicity were carried out as described in "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). *p<0.05, **p<0.01 versus collagen-stimulated human platelets. NS, not significant.
그림 Fig. 3. Effects of euchrestaflavanone B on [Ca²⁺]_i mobilization, IP₃RI phosphorylation, and serotonin release (A) Effect of euchrestaflavanone B on collagen-induced [Ca²⁺]_i mobilization. (B) Effect of euchrestaflavanone B on collagen-induced IP₃RI (Ser¹⁷⁵⁶) phosphorylation. (C) Effects of euchrestaflavanone B on collagen-induced serotonin release. [Ca²⁺]_i mobilization, serotonin release and Western blot were performed as described in "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). *p<0.05, **p<0.01 versus the collagen-stimulated human platelets.
그림 Fig. 4. Effects of euchrestaflavanone B on TXA₂ generation and cPLA₂-, p38-phosphorylation. (A) Effects of euchrestaflavanone B on collagen-induced TXA₂ generation. (B) Effect of euchrestaflavanone B on collagen-induced cPLA₂ (Ser⁵⁰⁵) phosphorylation. (C) Effect of euchrestaflavanone B on collagen-induced p38 phosphorylation. Measurement of TXA₂ generation and Western blot was performed as described in "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). *p<0.05, **p<0.01 versus the collagen-stimulated human platelets.
그림 Fig. 5. Effects of euchrestaflavanone B on fibrinogen binding and VASP-, Akt-phosphorylation (A) The flow cytometry histograms on fibrinogen binding. (B) Effect of euchrestaflavanone B on collagen-induced fibrinogen binding (%). (C) Effect of euchrestaflavanone B on collagen-induced VASP (Ser¹⁵⁷) phosphorylation. (D) Effect of euchrestaflavanone B on collagen-induced Akt (Ser⁴⁷³) phosphorylation. Measurement of fibrinogen binding and Western blot was carried out as described in "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). *p<0.05, **p<0.01 versus the collagen-stimulated human platelets.
#p<0.05 versus the unstimulated human PRP, ^†p<0.05 versus the thrombin-stimulated human PRP." alt="Fig. 6. Effects of euchrestaflavanone B on cyclic nucleotides and clot retraction (A) Effect of euchrestaflavanone B on cAMP production. (B) Effect of euchrestaflavanone B on cGMP production. (C) Photographs of fibrin clot (D) Effects of euchrestaflavanone B on thrombin-retracted fibrin clot (%). Measurement of cAMP/cGMP, clot retraction was performed as described in "Materials and Methods" section. The data are expressed as the mean ± standard deviation(n=4). *p<0.05 versus the collagen-stimulated human platelets. ^#p<0.05 versus the unstimulated human PRP, ^†p<0.05 versus the thrombin-stimulated human PRP." onerror="this.src='/images/noimg.png'" class="objectfit" /> 그림 Fig. 6. Effects of euchrestaflavanone B on cyclic nucleotides and clot retraction (A) Effect of euchrestaflavanone B on cAMP production. (B) Effect of euchrestaflavanone B on cGMP production. (C) Photographs of fibrin clot (D) Effects of euchrestaflavanone B on thrombin-retracted fibrin clot (%). Measurement of cAMP/cGMP, clot retraction was performed as described in "Materials and Methods" section. The data are expressed as the mean ± standard deviation(n=4). *p<0.05 versus the collagen-stimulated human platelets. ^#p<0.05 versus the unstimulated human PRP, ^†p<0.05 versus the thrombin-stimulated human PRP.

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