Chloroform fraction of Euphorbia maculata has antiplatelet activity via suppressing thromboxane B2 formation

Kwon,Se‑Uk; Cha,Ji‑Yoon; Lee,Hoon‑Yeon; Xin,Mingjie; Ji,Su‑Jeong; Kim,Dae‑Ki; Park,Do‑Sim; Pyo,Mi‑Kyung; Lee,Young‑Mi

doi:10.3892/mmr.2015.3319

Chloroform fraction of Euphorbia maculata has antiplatelet activity via suppressing thromboxane B2 formation

Authors:
- Se‑Uk Kwon
- Ji‑Yoon Cha
- Hoon‑Yeon Lee
- Mingjie Xin
- Su‑Jeong Ji
- Dae‑Ki Kim
- Do‑Sim Park
- Mi‑Kyung Pyo
- Young‑Mi Lee
View Affiliations

Affiliations: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang‑Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea, Department of Food Industry Convergence, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea, Department of Immunology and Institute of Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk 561‑180, Republic of Korea, Department of Laboratory Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea, International Ginseng and Herb Research Institute, Guemsan, Chungbuk 312‑804, Republic of Korea
Published online on: February 9, 2015 https://doi.org/10.3892/mmr.2015.3319
Pages: 4255-4261

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Euphorbia maculata (EM) is a traditionally used antidiarrheal, antibacterial, antifungal and antioxidant agent. However, the effects of EM on platelet activity remain to be elucidated. Therefore, the present study investigated the antiplatelet effect of various EM extract fractions on platelet aggregation in rats. The antiplatelet activity of the EM fractions on collagen or adenosine diphosphate (ADP)‑induced platelet aggregation was evaluated in vitro and ex vivo. Thromboxane B2 (TXB2) formation, rat‑tail bleeding time and coagulation time were also measured. Among the fractions, the chloroform fraction of EM (CFEM) significantly inhibited ADP‑induced platelet aggregation in vitro. Furthermore, oral administration of 50 mg/kg CFEM to rats significantly reduced ADP‑induced platelet aggregation without increasing the tail bleeding time or coagulation time. In addition, EM significantly inhibited the level of TXB2 formation in a dose‑dependent manner. These results suggest that CFEM exhibits antiplatelet activity, without causing bleeding, via the suppression of TXB2 formation. CFEM may be a type of food which has the potential for preventing cardiovascular disease.

View Figures

View References

1	Packham MA and Mustard JF: The role of platelets in the development and complication of atherosclerosis. Semin Hematol. 23:8–26. 1986.PubMed/NCBI
2	Ruggeri ZM: Mechanisms initiating platelet thrombus formation. Thromb Haemost. 78:611–616. 1997.PubMed/NCBI
3	Ruggeri ZM: Platelets in atherothrombosis. Nat Med. 8:1227–1234. 2002. View Article : Google Scholar : PubMed/NCBI
4	Brass LF: Thrombin and platelet activation. Chest. 124(Suppl 3): 18S–25S. 2003. View Article : Google Scholar : PubMed/NCBI
5	Lindholm LH and Mendis S: Prevention of cardiovascular disease in developing countries. Lancet. 370:720–722. 2007. View Article : Google Scholar : PubMed/NCBI
6	Furie B and Furie BC: Mechanisms of thrombus formation. N Engl J Med. 359:938–949. 2008. View Article : Google Scholar : PubMed/NCBI
7	Gross PL and Weitz JI: New antithrombotic drugs. Clin Pharmacol Ther. 86:139–146. 2009. View Article : Google Scholar : PubMed/NCBI
8	Collins B and Hollidge C: Antithrombotic drug market. Nat Rev Drug Discov. 2:11–12. 2003. View Article : Google Scholar : PubMed/NCBI
9	Gaglia MA Jr, Manoukian SV and Waksman R: Novel antiplatelet therapy. Am Heart J. 160:595–604. 2010. View Article : Google Scholar : PubMed/NCBI
10	Fong J, Cheng-Ching E, Hussain MS, Katzan I and Gupta R: Predictors of biochemical aspirin and clopidogrel resistance in patients with ischemic stroke. J Stroke Cerebrovasc Dis. 20:227–230. 2011. View Article : Google Scholar
11	Fitzgerald R and Pirmohamed M: Aspirin resistance: effect of clinical, biochemical and genetic factors. Pharmacol Ther. 130:213–225. 2011. View Article : Google Scholar : PubMed/NCBI
12	Barrett NE, Holbrook L, Jones S, et al: Future innovations in antiplatelet therapies. Br J Pharmacol. 154:918–939. 2008. View Article : Google Scholar : PubMed/NCBI
13	Jackson SP and Schoenwaelder SM: Antiplatelet therapy: in search of the ‘magic bullet’. Nat Rev Drug Discov. 2:775–789. 2003. View Article : Google Scholar : PubMed/NCBI
14	Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al: Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 49:1505–1516. 2007. View Article : Google Scholar : PubMed/NCBI
15	Tsai IL, Lin WY, Teng CM, et al: Coumarins and antiplatelet constituents from the root bark of Zanthoxylum schinifolium. Planta Med. 66:618–623. 2000. View Article : Google Scholar : PubMed/NCBI
16	Ballabeni V, Tognolini M, Bertoni S, et al: Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam) Kosterm (Lauraceae) calices from Amazonian Ecuador. Pharmacol Res. 55:23–30. 2007. View Article : Google Scholar
17	Seo EJ, Lee DU, Kwak JH, et al: Antiplatelet effects of Cyperus rotundus and its component (+)-nootkatone. J Ethnopharmacol. 135:48–54. 2011. View Article : Google Scholar : PubMed/NCBI
18	Fuentes E and Palomo I: Relationship between platelet PPARs, cAMP levels, and P-Selectin expression: Antiplatelet activity of natural products. Evid Based Complement Alternat Med. 2013:8617862013. View Article : Google Scholar : PubMed/NCBI
19	Fuentes E, Caballero J, Alarcón M, Rojas A and Palomo I: Chlorogenic acid inhibits human platelet activation and thrombus formation. PLoS One. 9:e906992014. View Article : Google Scholar : PubMed/NCBI
20	Yoshiaki A, Keita K, Tsutomu H, et al: Four new hydrolysable tannins and an acylated flavonol glycoside from Euphorbia maculate. Can J Chem. 75:727–733. 1997. View Article : Google Scholar
21	Cao X, Wang W, Zhou L, Cui X and Song X: Comparison on mass fraction of total flavonoids and tannin of three kinds of herba Euphorbiae Humifusae and their antibacaterial activity in vitro. Acta Agriculturae Boreali-Occidentalis Sinica. 21:184–188. 2012.
22	Kuerbannisha M, Zulipiya T, Gulina D, Xieraili T and Silafu A: Determination of rutin and quercitrin in the antifungal extract from Euphorbia maculate. Lishizhen Medicine and Materia Medica Research. 22:2584–2585. 2011.
23	Liu S, Jiang D and Li L: Research on the total flavonoids’ content and antioxidant activity of Euphorbia maculata and Euphorbia humifusae. J Hunan Agr U Nat Sci. 33:287–288. 2007.
24	Lee BK, Lee DH, Park S, et al: Effects of KR-33028, a novel Na⁺/H⁺ exchanger-1 inhibitor, on glutamate-induced neuronal cell death and ischemia-induced cerebral infarct. Brain Res. 1248:22–30. 2009. View Article : Google Scholar
25	Ryu KH, Han HY, Lee SY, et al: Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time. Thromb Res. 124:328–334. 2009. View Article : Google Scholar : PubMed/NCBI
26	Mustard JF, Perry DW, Ardlie NG and Packham MA: Preparation of suspensions of washed platelets from humans. Br J Haematol. 22:193–204. 1972. View Article : Google Scholar : PubMed/NCBI
27	Lee BJ, Jo IY, Bu Y, et al: Antiplatelet effect of Spatholobus suberectus via inhibition of glycoprotein II_b/III_a receptor. J Ethnopharmacol. 134:460–467. 2011. View Article : Google Scholar : PubMed/NCBI
28	Cho J, Furie BC, Coughlin SR and Furie B: A critical role for extracellular protein disulfide isomerase during thrombus formation in mice. J Clin Invest. 118:1123–1131. 2008.PubMed/NCBI
29	Majid A, Delanty N and Kantor J: Antiplatelet agents for secondary prevention of ischemic stroke. Ann Pharmacother. 35:1241–1247. 2001. View Article : Google Scholar : PubMed/NCBI
30	Wijns W, Kolh P, Danchin N, et al: Guidelines on myocardial revascularization. Eur Heart J. 31:2501–2555. 2010. View Article : Google Scholar : PubMed/NCBI
31	Albers GW and Amarenco P: Combination therapy with clopidogrel and aspirin: can the cure results be extrapolated to cerebrovascular patients? Stroke. 32:2948–2949. 2001. View Article : Google Scholar : PubMed/NCBI
32	Jin YR, Hwang KA, Cho MR, et al: Antiplatelet and antithrombotic activities of CP201, a newly synthesized 1,4-naphthoquinone derivative. Vasc Pharmcol. 41:35–41. 2004. View Article : Google Scholar
33	Kunapuli SP, Dorsam RT, Kim S and Quinton TM: Platelet purinergic receptors. Curr Opin Pharmacol. 3:175–180. 2003. View Article : Google Scholar : PubMed/NCBI
34	Hollopeter G, Jantzen HM, Vincent D, Li G, England L and Ramakrishnan V: Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 409:202–207. 2001. View Article : Google Scholar : PubMed/NCBI
35	Gachet C: P2 receptors, platelet function and pharmacological implications. Thromb Haemost. 99:466–472. 2008.PubMed/NCBI
36	Cattaneo M: Platelet P2 receptors: old and new targets for antithrombotic drugs. Expert Rev Cardiovasc Ther. 5:45–55. 2007. View Article : Google Scholar
37	Cattaneo M: New P2Y12 blockers. J Thromb Haemost. 7(Suppl 1): 262–265. 2009. View Article : Google Scholar : PubMed/NCBI
38	Jakubowski JA, Winters KJ, Naganuma H and Wallentin L: Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev. 25:357–374. 2007. View Article : Google Scholar : PubMed/NCBI
39	Akiyama H, Kudo S and Shimizu T: The absorption, distribution and excretion of a new antithrombotic and vasodilating agent, cilostazol, in rat, rabbit, dog and man. Arzneimittelforschung. 35:1124–1132. 1985.PubMed/NCBI
40	Li Y and Wang N: Antithrombotic effects of Danggui, Honghua and potential drug interaction with clopidogrel. J Ethnopharmacol. 128:623–628. 2010. View Article : Google Scholar : PubMed/NCBI
41	Renné T, Nieswandt B and Gailani D: The intrinsic pathway of coagulation is essential for thrombus stability in mice. Blood Cell Mol Dis. 36:148–151. 2006. View Article : Google Scholar
42	Azevedo AP, Farias JC, Costa GC, et al: Anti-thrombotic effect of chronic oral treatment with Orbignya phalerata Mart. J Ethnopharmacol. 111:155–159. 2007. View Article : Google Scholar
43	Mann KG: Thrombin: can’t live without it; probably die from it. Chest. 124(Suppl 3): 1S–3S. 2003. View Article : Google Scholar
44	Jennings LK: Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost. 102:248–257. 2009.PubMed/NCBI
45	Mitchell MD, Bibby JG, Hicks BR, et al: Thromboxane B2 and human parturition: concentrations in the plasma and production in vitro. J Endocrinol. 78:435–441. 1978. View Article : Google Scholar : PubMed/NCBI
46	Storey RF, Judge HM, Wilcox RG and Heptinstall S: Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin. Thromb Haemost. 88:488–494. 2002.PubMed/NCBI
47	Barton JF, Hardy AR, Poole AW and Mundell SJ: Reciprocal regulation of platelet responses to P2Y and thromboxane receptor activation. J Thromb Haemost. 6:534–543. 2008. View Article : Google Scholar
48	Viinikka L and Ylikorkala O: Measurement of thromboxane B2 in human plasma or serum by radioimmunoassay. Prostaglandins. 20:759–766. 1980. View Article : Google Scholar : PubMed/NCBI
49	Plow EF and Ginsberg MH: Cellular adhesion: GPIIb/IIIa as a prototypic adhesion receptor. Prog Hemost Thromb. 9:117–156. 1989.
50	Helft G, Gilard M, Feuvre Le C and Zaman AG: Drug insight: antithrombotic therapy after percutaneous coronary intervention in patients with an indication or anticoagulation. Nat Clin Pract Cardiovasc Med. 3:673–680. 2006. View Article : Google Scholar : PubMed/NCBI