BMC Complementary and Alternative Medicine | |
Anti-thrombotic effects of α-linolenic acid isolated from Zanthoxylum bungeanum Maxim seeds | |
Siwang Wang1  Yanhua Xie1  Wei Cao1  Xuanxuan Zhou1  Weidong Cao2  Qian Yang1  | |
[1] Department of Materia Medica, School of Pharmacology, Fourth Military Medical University, Xi’an, Shaanxi, China;Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China | |
关键词: Unsaturated fatty acids; Linoleic acid; Zanthoxylum bungeanum Maxim seeds; Anti-thrombotic; Alpha-linolenic acid; | |
Others : 1086630 DOI : 10.1186/1472-6882-14-348 |
|
received in 2014-05-28, accepted in 2014-09-16, 发布年份 2014 | |
【 摘 要 】
Background
The current study was to evaluate the anti-thrombotic effect of alpha-linolenic acid (ALA) which was isolated and purified from Jiaomu in vivo.
Methods
The seeds were crushed and subsequently subjected to saponification, acid hydrolysis, gradient freezing, urea inclusion and complexation of silver nitrate to obtain the unsaturated fatty acids. The chemical characteristics of isolated ALA were validated by 1HNMR, 13CNMR and mass spectrometry, and then the anti-thrombotic effect of ALA and its mixture with linoleic acid (1:1) were evaluated in the following experiments.
Results
The alpha-linolenic acid was isolated and purified from Jiaomu through our newly established methods. ALA and its mixture with linoleic acid can prolong the hemorrhage and coagulation time as well as enhanced the survival rate of mice subjected to collagen-adrenaline induced thrombosis. In addition, the thrombosis on A-V bypass and platelet aggregation of rats will be reduced after treated with ALA or its mixture, and the expression level of Akt and PI3K protein decreased 26% and 31%, respectively.
Conclusions
We designed and optimized a very simple and high-yield procedure to isolate ALA and linoleic acid mixture from seeds of Zanthoxylum bungeanum Maxim and demonstrated that such mixture can obtain a good anti-thrombotic effect through the modulation of PI3K/Akt signaling.
【 授权许可】
2014 Yang et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150116013610922.pdf | 1057KB | download | |
Figure 4. | 49KB | Image | download |
Figure 3. | 82KB | Image | download |
Figure 2. | 88KB | Image | download |
Figure 1. | 41KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]Deckelbaum RJ, Torrejon C: The omega-3 fatty acid nutritional landscape: health benefits and sources. J Nutr 2012, 142:587S-591S.
- [2]Rao S, Abdel-Reheem M, Bhella R, McCracken C, Hildebrand D: Characteristics of high alpha-linolenic acid accumulation in seed oils. Lipids 2008, 43:749-755.
- [3]Arshad A, Al-Leswas D, Stephenson J, Metcalfe M, Dennison A: Potential applications of fish oils rich in n-3 fatty acids in the palliative treatment of advanced pancreatic cancer. Br J Nutr 2011, 106:795-800.
- [4]Meijerink J, Balvers M, Witkamp R: N-acyl amines of docosahexaenoic acid and other n-3 polyunsatured fatty acids - from fishy endocannabinoids to potential leads. Br J Pharmacol 2013, 169:772-783.
- [5]Albert CM, Oh K, Whang W, Manson JE, Chae CU, Stampfer MJ, Willett WC, Hu FB: Dietary alpha-linolenic acid intake and risk of sudden cardiac death and coronary heart disease. Circulation 2005, 112:3232-3238.
- [6]Harris WS: Extending the cardiovascular benefits of omega-3 Fatty acids. Curr Atheroscler Rep 2005, 7:375-380.
- [7]Das UN: Essential fatty acids: biochemistry, physiology and pathology. Biotechnol J 2006, 1:420-439.
- [8]Pan A, Chen M, Chowdhury R, Wu JH, Sun Q, Campos H, Mozaffarian D, Hu FB: α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 2012, 96:1262-1273.
- [9]Poudyal H, Panchal SK, Diwan V, Brown L: Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. Prog Lipid Res 2011, 50:372-387.
- [10]Li Y, Zeng J, Liu L, Jin X: GC-MS analysis of supercritical carbon dioxide extraction products from pericarp of Zanthoxylum bungeanum. Zhong Yao Cai 2001, 24:572-573.
- [11]Li GH, Fu LM, Xue KF: Examination of the chemical composition of the seeds of Zanthoxylum bungeeanum Maxim. J Zhengzhou Grain College 1994, 15:21-23.
- [12]Zhuang SH, Li ML: Ingredient analysis of prickly ash seed oil. Acta Agriculturae Boreali-occidentalis Sinica 2002, 11:43-45.
- [13]Hook KM, Bennett JS: Glycoprotein IIb/IIIa antagonists. Handb Exp Pharmacol 2012, 210:199-223.
- [14]Lippi G, Montagnana M, Danese E, Favaloro EJ, Franchini M: Glycoprotein IIb/IIIa inhibitors: an update on the mechanism of action and use of functional testing methods to assess antiplatelet efficacy. Biomark Med 2011, 5:63-70.
- [15]Ciborowski M, Tomasiak M: The in vitro effect of eptifibatide, a glycoprotein IIb/IIIa antagonist, on various responses of porcine blood platelets. Acta Pol Pharm 2009, 66:235-242.
- [16]Kisucka J, Chauhan AK, Zhao BQ, Patten IS, Yesilaltay A, Krieger M, Wagner DD: Elevated levels of soluble P-selectin in mice alter blood–brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood 2009, 113:6015-6022.
- [17]Dona M, Fredman G, Schwab JM, Chiang N, Arita M, Goodarzi A, Cheng G, von Andrian UH, Serhan CN: Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 2008, 112:848-855.
- [18]Miszti-Blasius K, Debreceni IB, Felszeghy S, Dezso B, Kappelmayer J: Lack of P-selectin glycoprotein ligand-1 protects mice from thrombosis after collagen/epinephrine challenge. Thromb Res 2011, 127:228-234.
- [19]Umar A, Guerin V, Renard M, Boisseau M, Garreau C, Begaud B, Molimard M, Moore N: Effects of armagnac extracts on human platelet function in vitro and on rat arteriovenous shunt thrombosis in vivo. Thromb Res 2003, 110:135-140.
- [20]Chen G, Fei X, Ling J: The effects of aminoglycoside antibiotics on platelet aggregation and blood coagulation. Clin Appl Thromb Hemost 2012, 18:538-541.
- [21]Oh WJ, Endale M, Park SC, Cho JY, Rhee MH: Dual Roles of Quercetin in Platelets: Phosphoinositide-3-Kinase and MAP Kinases Inhibition, and cAMP-Dependent Vasodilator-Stimulated Phosphoprotein Stimulation. Evid Based Complement Alternat Med 2012, 2012:485262.
- [22]Zhang HM, Liu FZ, Dai LM: Parity method of α-linlenic acid based on the theory of urea addution fractionation(i)-study on the purification process with orthogonal experiment. China Oils Fats 2001, 26:41-44.
- [23]Renaud S, Lanzmann-Petithory D: Dietary fats and coronary heart disease pathogenesis. Curr Atheroscler Rep 2002, 4:419-424.
- [24]Moore SF, Hunter RW, Harper MT, Savage JS, Siddiq S, Westbury SK, Poole AW, Mumford AD, Hers I: Dysfunction of the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway underlies ex vivo platelet hypoactivity in essential thrombocythemia. Blood 2013, 121:1209-1219.
- [25]Schaff M, Receveur N, Bourdon C, Ohlmann P, Lanza F, Gachet C, Mangin PH: β-arrestin-1 participates in thrombosis and regulates integrin aIIbβ3 signalling without affecting P2Y receptors desensitisation and function. Thromb Haemost 2012, 107:735-748.
- [26]Park JY, Ji HD, Jeon BR, Im EJ, Son YM, Lee JY, Lee DH, Lee YC, Hyun E, Jia Q, Hong M, Park HJ, Rhee MH: Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production. Evid Based Complement Alternat Med 2013, 2013:569160.
- [27]Hadas K, Randriamboavonjy V, Elgheznawy A, Mann A, Fleming I: Methylglyoxal induces platelet hyperaggregation and reduces thrombus stability by activating PKC and inhibiting PI3K/Akt pathway. PLoS One 2013, 8:e74401.