Brazilin isolated from Caesalpinia sappan L. acts as a novel collagen receptor agonist in human platelets
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- 作者：Yi Chang (1) (2)
Steven Kuan-Hua Huang (3)
Wan-Jung Lu (4) (5)
Chi-Li Chung (6) (7)
Wei-Lin Chen (4) (5)
Shun-Hua Lu (4) (5)
Kuan-Hung Lin (4) (8)
Joen-Rong Sheu (4) (5) - 关键词：Brazilin ; Collagen receptors ; Lyn phosphorylation ; Occlusion time ; Platelet activation
- 刊名：Journal of Biomedical Science
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：20
- 期：1
- 全文大小：399KB
- 参考文献：1. Baek NI, Jeon SG, Ahn EM, Hahn JT, Bahn JH, Jang JS, Cho SW, Park JK, Choi SY:
2. Moon CK, Yun YP, Lee JH, Wagner H, Shin YS:
3. Xie YW, Ming DS, Xu HX, Dong H, But PP:
4. Hu CM, Kang JJ, Lee CC, Li CH, Liao JW, Cheng YW:
5. Zheng MS, Zhang YZ:
6. Shih IM, Chiang HS, Yang LL, Wang TL:
7. Puchtler H, Meloan SN, Waldrop FS:
8. Kim SG, Kim YM, Khil LY, Jeon SD, So DS, Moon CH, Moon CK:
9. Moon CK, Park KS, Kim SG, Won HS, Chung JH:
10. Bae IK, Min HY, Han AR, Seo EK, Lee SK:
11. Sheu JR, Hung WC, Wu CH, Ma MC, Kan YC, Lin CH, Lin MS, Luk HN, Yen MH:
12. Jackson SP, Nesbitt WS, Kulkarni S:
13. Hwang GS, Kim JY, Chang TS, Jeon SD, So DS, Moon CK:
14. Hsiao G, Lin KH, Chang Y, Chen TL, Tzu NH, Chou DS, Sheu JR:
15. Chou DS, Hsiao G, Shen MY, Tsai YJ, Chen TF, Sheu JR:
16. Moroi M, Jung SM:
17. Hsiao G, Lee JJ, Lin KH, Shen CH, Fong TH, Chou DS, Sheu JR:
18. Singer WD, Brown HA, Sternweis PC:
19. Niedergang F, Alcover A, Knight CG, Farndale RW, Barnes MJ, Francischetti IM, Bon C, Leduc M:
20. Huang TF, Liu CZ, Yang SH:
21. Stegner D, Nieswandt B:
22. Hirano K:
23. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR:
24. Lalau Keraly C, Kinlough-Rathbone RL, Packham MA, Suzuki H, Mustard JF:
25. Chang CH, Chung CH, Kuo HL, Hsu CC, Huang TF:
26. Chung CH, Wu WB, Huang TF:
27. He L, Pappan LK, Grenache DG, Li Z, Tollefsen DM, Santoro SA, Zutter MM:
28. Nieswandt B, Watson SP:
29. Ezumi Y, Shindoh K, Tsuji M, Takayama H:
30. Suzuki-Inoue K, Tulasne D, Shen Y, Bori-Sanz T, Inoue O, Jung SM, Moroi M, Andrews RK, Berndt MC, Watson SP:
31. Conn PJ, Christopoulos A, Lindsley CW:
32. Carlsson LE, Santoso S, Spitzer C, Kessler C, Greinacher A:
33. Benze G, Heinrich J, Schulte H, Rust S, Nowak-Gottl U, Tataru MC, Kohler E, Assmann G, Junker R:
34. Nieswandt B, Schulte V, Bergmeier W, Mokhtari-Nejad R, Rackebrandt K, Cazenave JP, Ohlmann P, Gachet C, Zirngibl H: - 作者单位：Yi Chang (1) (2)
Steven Kuan-Hua Huang (3)
Wan-Jung Lu (4) (5)
Chi-Li Chung (6) (7)
Wei-Lin Chen (4) (5)
Shun-Hua Lu (4) (5)
Kuan-Hung Lin (4) (8)
Joen-Rong Sheu (4) (5)
1. Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Rd, Taipei, 11101, Taiwan
2. School of Medicine, Fu-Jen Catholic University, 510 Zhong-Zheng Rd, Taipei, 24205, Taiwan
3. Division of Urology, Department of Surgery, Chi-Mei Medical Center, 901 Zhong-Hua Rd, Tainan, 71004, Taiwan
4. Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing St, Taipei, 11031, Taiwan
5. Graduate Institute Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing St, Taipei, 11031, Taiwan
6. Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, 252 Wu-Hsing St, Taipei, 11031, Taiwan
7. School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wu-Hsing St, Taipei, 11031, Taiwan
8. Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen-Chang Rd, Taipei, 11101, Taiwan - ISSN：1423-0127
文摘
Background Brazilin, isolated from the heartwood of Caesalpinia sappan L., has been shown to possess multiple pharmacological properties. Methods In this study, platelet aggregation, flow cytometry, immunoblotting analysis, and electron spin resonance (ESR) spectrometry were used to investigate the effects of brazilin on platelet activation ex vivo. Moreover, fluorescein sodium-induced platelet thrombi of mesenteric microvessels was also used in in vivo study. Results We demonstrated that relatively low concentrations of brazilin (1 to 10 μM) potentiated platelet aggregation induced by collagen (0.1 μg/ml) in washed human platelets. Higher concentrations of brazilin (20 to 50 μM) directly triggered platelet aggregation. Brazilin-mediated platelet aggregation was slightly inhibited by ATP (an antagonist of ADP). It was not inhibited by yohimbine (an antagonist of epinephrine), by SCH79797 (an antagonist of thrombin protease-activated receptor [PAR] 1), or by tcY-NH2 (an antagonist of PAR 4). Brazilin did not significantly affect FITC-triflavin binding to the integrin αIIbβ3 in platelet suspensions. Pretreatment of the platelets with caffeic acid phenethyl ester (an antagonist of collagen receptors) or JAQ1 and Sam.G4 monoclonal antibodies raised against collagen receptor glycoprotein VI and integrin α2β1, respectively, abolished platelet aggregation stimulated by collagen or brazilin. The immunoblotting analysis showed that brazilin stimulated the phosphorylation of phospholipase C (PLC)γ2 and Lyn, which were significantly attenuated in the presence of JAQ1 and Sam.G4. In addition, brazilin did not significantly trigger hydroxyl radical formation in ESR analysis. An in vivo mouse study showed that brazilin treatment (2 and 4 mg/kg) significantly shortened the occlusion time for platelet plug formation in mesenteric venules. Conclusion To the best of our knowledge, this study provides the first evidence that brazilin acts a novel collagen receptor agonist. Brazilin is a plant-based natural product, may offer therapeutic potential as intended anti-thrombotic agents for targeting of collagen receptors or to be used a useful tool for the study of detailed mechanisms in collagen receptors-mediated platelet activation.