[논문]Esculetin이 PI3K/MAPK 경로 하향 조절을 통해 collagen 유도의 혈소판 응집 억제에 미치는 효과

박창은; 이동하

doi:10.22889/kjp.2021.52.3.127

Esculetin이 PI3K/MAPK 경로 하향 조절을 통해 collagen 유도의 혈소판 응집 억제에 미치는 효과
Inhibitory Effects of Esculetin Through the Down-Regulation of PI3K/MAPK Pathway on Collagen-Induced Platelets Aggregation 원문보기

생약학회지, v.52 no.3, 2021년, pp.127 - 133

박창은 (남서울대학교 임상병리학과.분자진단연구소) , 이동하 (남서울대학교 임상병리학과.분자진단연구소)

Abstract ▼ AI-Helper

Platelet activation plays a major role in cardiovascular disorders (CVDs). Thus, disrupting platelet activation represents an attractive therapeutic target on CVDs. Esculetin, a bioactive 6,7-dihydroxy derivative of coumarin, possesses pharmacological activities against obesity, diabetes, renal failure, and CVDs. In other report, the effect of esculetin has been examined in human platelet activation and experimental mouse models, and esculetin inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets. However, it had no effects on other agonists such as thrombin and U46619, and its mechanism is not also clearly known. This study investigated the effect of esculetin on collagen-induced human platelet aggregation, and we clarified the mechanism. Esuletin has effects on the down regulation of PI3K/Akt and MAPK, phosphoproteins that act in the signaling process in platelet aggregation. The effects of esculetin reduced of TXA2 production and phospholipase A2 activation, and intracellular granule secretion including ATP and serotonin, leading to inhibit platelet aggregation. These results clearly clarified the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

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표/그림 (6)

그림 Fig. 1. The structure of esculetin and its mechanism. PIN: 6,7- Dihydroxy-2H-1-benzopyran-2-one, Chemical formula: C₉H₆O₄, Molar mass: 178.14 g/mole.
그림 Fig. 2. Effects of esculetin platelet aggregation and cytotoxicity. (A) Effect of esculetin on the aggregation collagen-induced human platelets. (B) Half-maximal inhibitory concentration (IC₅₀) value of esculetin in collagen-induced human platelet aggregation. (C) Effect of esculetin on cytotoxicity. The aggregation of platelets and cytotoxicity were performed as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). *p<0.05, **p<0.001 versus collagen-stimulated human platelets. NS, not significant.
ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." alt="Fig. 3. Effects of esculetin on PI3K and Akt phosphorylation. Western blot was carried out as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." onerror="this.src='/images/noimg.png'" class="objectfit" /> 그림 Fig. 3. Effects of esculetin on PI3K and Akt phosphorylation. Western blot was carried out as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets.
ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." alt="Fig. 4. Effects of esculetin on MAPK phosphorylation. Western blot was carried out as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." onerror="this.src='/images/noimg.png'" class="objectfit" /> 그림 Fig. 4. Effects of esculetin on MAPK phosphorylation. Western blot was carried out as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets.
ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." alt="Fig. 5. Effects of esculetin on PLA₂ phosphorylation and TXA₂ generation. (A) Effect of esuletin on collagen-induced PLA₂ phosphorylation. (B) Effect of esculetin on collagen-induced TXA₂ generation. TXA₂ generation measurement and Western blot was performed as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." onerror="this.src='/images/noimg.png'" class="objectfit" /> 그림 Fig. 5. Effects of esculetin on PLA₂ phosphorylation and TXA₂ generation. (A) Effect of esuletin on collagen-induced PLA₂ phosphorylation. (B) Effect of esculetin on collagen-induced TXA₂ generation. TXA₂ generation measurement and Western blot was performed as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets.
ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." alt="Fig. 6. Effects of esculetin on granule secretion. (A) Effects of esculetin on ATP release. (B) Effects of esculetin on serotonin release. Measurement of granule secretion was carried out as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets." onerror="this.src='/images/noimg.png'" class="objectfit" /> 그림 Fig. 6. Effects of esculetin on granule secretion. (A) Effects of esculetin on ATP release. (B) Effects of esculetin on serotonin release. Measurement of granule secretion was carried out as stated in the "Materials and Methods" section. The data are expressed as the mean ± standard deviation (n=4). ^ap<0.05 versus non-stimulated platelets, *p<0.05, **p<0.001 versus the collagen-stimulated human platelets.

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데이터처리

통계 분석 - 측정된 모든 실험 결과를 평균 ± SD로 처리하고 ANOVA(분산 분석)로 분석하였다

이론/모형

통계 분석 - 측정된 모든 실험 결과를 평균 ± SD로 처리하고 ANOVA(분산 분석)로 분석하였다. 그룹간 평균값에 유의한 차이가 있는 경우에는 Newman-Keuls 방법으로 비교하여 그룹별로 표시하였다. 결과가 p<0.

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