药学学报, 2021, 56(2): 368-373
引用本文:
阿瓦古丽·达吾提, 方莲花, 杜冠华. 丹酚酸对缺血性心脏病的作用及作用机制研究进展[J]. 药学学报, 2021, 56(2): 368-373.
DAWUTI Awaguli, FANG Lian-hua, DU Guan-hua. Research advances on the protective effects and mechanism of salvianolic acids against ischemic heart disease[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 368-373.

丹酚酸对缺血性心脏病的作用及作用机制研究进展
阿瓦古丽·达吾提, 方莲花, 杜冠华
中国医学科学院、北京协和医学院药物研究所, 北京市药物靶点研究与新药筛选重点实验室, 北京 100050
摘要:
丹酚酸为唇形科植物丹参的最主要的水溶性活性成分,具有多种药理作用,被广泛应用于防治心血管疾病。本文通过查阅国内外最新研究文献,对丹酚酸防治缺血性心脏病的作用及作用机制进行综述,并介绍了丹酚酸A和丹酚酸B等丹参的主要水溶性成分通过保护血管内皮、舒张冠状动脉、促进血管再生、抗血小板聚集、抑制炎性反应、抗细胞凋亡和清除自由基等多角度防治缺血性心脏病的作用机制,为进一步研究丹酚酸对缺血性心脏病的作用及药物研发提供理论依据。
关键词:    丹参      水溶性成分      丹酚酸A      丹酚酸B      缺血性心脏病     
Research advances on the protective effects and mechanism of salvianolic acids against ischemic heart disease
DAWUTI Awaguli, FANG Lian-hua, DU Guan-hua
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Salvianolic acids are the main water-soluble active compounds of Salvia miltiorrhiza and have been widely used for the treatment of cardiovascular diseases. Based on the latest studies in China and abroad, we summarize the pharmacological effects and mechanism of salvianolic acids on ischemic heart disease by describing how salvianolic acid A and salvianolic acid B protect the vascular endothelium, relax coronary arteries, promote angiogenesis and anti-platelet aggregation, inhibit the inflammatory response, anti-cell apoptosis, and scavenge free radicals. This review provides a theoretical basis for further research on the effects of salvianolic acids on ischemic heart disease and their potential for drug development.
Key words:    Salvia miltiorrhiza    water-soluble component    salvianolic acid A    salvianolic acid B    ischemic heart disease   
收稿日期: 2020-08-01
DOI: 10.16438/j.0513-4870.2020-1277
基金项目: 国家自然科学基金资助项目(81773935);中国医学科学院医学与健康科技创新工程项目(2017-I2M-1-010,2016-I2M-3-007);国家科技重大专项(2018ZX09711001-010,2017ZX09101001).
通讯作者: 方莲花,Tel/Fax:86-10-63165313,E-mail:fanglh@imm.ac.cn;杜冠华,Tel/Fax:86-10-63165184,E-mail:dugh@imm.ac.cn
Email: fanglh@imm.ac.cn;dugh@imm.ac.cn
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参考文献:
[1] Nowbar AN, Gitto M, Howard JP, et al. Mortality from ischemic heart disease[J]. Circ Cardiovasc Qual Outcomes, 2019, 12:e005375.
[2] Zhou MG, Wang HD, Zeng XY, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017:a systematic analysis for the global burden of disease study 2017[J]. Lancet, 2019, 394:1145-1158.
[3] Stanaway JD, Afshin A, Gakidou E, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017:a systematic analysis for the global burden of disease study 2017[J]. Lancet, 2018, 392:1923-1994
[4] MEIm XD, Cao YF, Che YY, et al. Danshen:a phytochemical and pharmacological overview[J]. Chin J Nat Med, 2019, 17:59-80.
[5] Du GH, Song JK, Du LD, et al. Chemical and pharmacological research on the polyphenol acids isolated from Danshen:a review of salvianolic acids[J]. Adv Pharmacol, 2020, 87:1-41.
[6] Li ZM, Xu SW, Liu PQ. Salvia miltiorrhiza Burge (Danshen):a golden herbal medicine in cardiovascular therapeutics[J]. Acta Pharmacol Sin, 2018, 39:802-824.
[7] Mandeep S, Boden WE, Padala SK, et al. Role of short-acting nitroglycerin in the management of ischemic heart disease[J]. Drug Des Devel Ther, 2015, 9:4793-4805.
[8] Han X, Liu D, Feng L, et al. Protective effect of seven kinds of phenolic acids of total salvianolic acids components on human umbilical vein endothelial cells with hypoxic injury[J]. Chin J Chin Mater Med (中国中药杂志), 2016, 41:1107-1112.
[9] Dan Y, Peng Z, Ting F, et al. SalA attenuates ischemia/reperfusion-induced endothelial barrier dysfunction via down-regulation of VLDL receptor expression[J]. Cell Physiol Biochem, 2014, 33:747-757.
[10] Xie P, Duan Y, Guo X, et al. SalA attenuates hypoxia-induced endothelial endoplasmic reticulum stress and apoptosis via down-regulation of VLDL receptor expression[J]. Cell Physiol Biochem, 2015, 35:17-28.
[11] Zhu J, Jia X, Kang L. Effect of salvianolic acid B on contraction of porcine coronary artery[J]. Tianjin J Tradit Chin Med (天津中医药), 2010, 27:418-420.
[12] Pan C, Lou L, Huo Y, et al. Salvianolic acid B and tanshinone IIA attenuate myocardial ischemia injury in mice by NO production through multiple pathways[J]. Ther Adv Cardiovasc Dis, 2011, 5:99-111.
[13] Xu BH. The Effects of Sal B on Angiogenesis in Ischemic Myocardium of Rats and the Tension of Thoracic Aortic Ring in Normal Rats (丹酚酸B对心肌缺血大鼠血管新生及对正常大鼠离体胸主动脉环张力的影响)[D]. Nanjing:Nanjing University of Chinese Medicine, 2012.
[14] Johnson T, Zhao L, Manuel G, et al. Approaches to therapeutic angiogenesis for ischemic heart disease[J]. J Mol Med, 2019, 97:141-151.
[15] Yu L, Zhang K, Zhu J, et al. Salvianolic acid exerts cardioprotection through promoting angiogenesis in animal models of acute myocardial infarction:preclinical evidence[J]. Oxid Med Cell Longev, 2017, 2017:5427657.
[16] Juan L, Duan C, Liu J. Salvianolic acid A promotes the acceleration of neovascularization in the ischemic rat myocardium and the functions of endothelial progenitor cells[J]. J Ethnopharmacol, 2014, 151:218-227.
[17] Chen HX, Xu LI, Xu BH. Effect of salvianolic acid B on angiogenesis of ischemic myocardium in myocardial ischemia rats[J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2012, 18:180-183.
[18] Zhou D, Tian T, Shu Q, et al. Effect of salvianolic acid B on angiogenesis of myocardial ischemia in rats[J]. Chin Tradit Herb Drugs (中草药), 2018, 49:5166-5169.
[19] Guo H, Cui G, Tian J, et al. Transplantation of salvianolic acid B pretreated mesenchymal stem cells improves cardiac function in rats with myocardial infarction through angiogenesis and paracrine mechanisms[J]. Int J Cardiol, 2014, 177:538-542.
[20] Li QW, Tan JZ, Nan YY, et al. Effects of EPCs preconditioned with salvianolic acid B combined with BMSC transplantation into infracted myocardium on expression of cardiac muscle VEGF and bFGF protein in rats[J]. Tianjin J Tradit Chin Med (天津中医药), 2009, 26:57-59.
[21] Wang H, Kong L, Wang R, et al. Comparison of antithrombotic effects between salvianolic acid A and aspirin[J]. Acta Pharm Sin (药学学报), 2019, 54:301-307.
[22] Huang Z, Zeng C, Zhu L, et al. Salvianolic acid A inhibits platelet activation and arterial thrombosis via inhibition of phosphoinositide 3-kinase[J]. J Thromb Haemost, 2010, 8:1383-1393.
[23] Fan H, Fu F, Yang M, et al. Antiplatelet and antithrombotic activities of salvianolic acid A[J]. Thromb Res, 2010, 126:e17-e22.
[24] Yuan X, Xiang Y, Zhu N, et al. Salvianolic acid A protects against myocardial ischemia/reperfusion injury by reducing platelet activation and inflammation[J]. Exp Ther Med, 2017, 14:961-966.
[25] Liu X, Gao Z, Wu Y, et al. Salvianolic acids from antithrombotic traditional Chinese medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors[J]. Sci Rep, 2018, 8:8084.
[26] Liu L, Li J, Zhang Y, et al. Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor:evidence from clinic to laboratory[J]. Thromb Res, 2014, 134:866-876.
[27] Chang Q, Guo Y, You Y, et al. Influence of fluid shear stress on anti-platelet aggregation of salvianolic acid B[J]. J Med Biomech (医用生物力学), 2013, 28:344-349.
[28] Vachiat A, Mccutcheon K, Tsabedze N, et al. HIV and ischemic heart disease[J]. J Am Coll Cardiol, 2017, 69:73-82.
[29] Wu Z, Huang Z, Jin W, et al. Peripheral inflammatory biomarkers for myocardial infarction risk:a prospective community-based study[J]. Clin Chem, 2017, 63:663-672.
[30] Zhou R, Gao J, Xiang C, et al. Salvianolic acid A attenuated myocardial infarction-induced apoptosis and inflammation by activating Trx[J]. Naunyn Schmiedebergs Arch Pharmacol, 2020, 393:991-1002.
[31] Ma Q, Yang Q, Chen J, et al. Salvianolic acid A ameliorates early-stage atherosclerosis development by inhibiting NLRP3 inflammasome activation in Zucker diabetic fatty rats[J]. Molecules, 2020, 25:1089.
[32] Zhang Y, Zhang T, Guo L, et al. Study on the dose and time effects of salvianolic acid B on TLR4-NFκB-TNFα pathway in neonatal rat cardiomyocytes damaged by hypoxia[J]. World Chin Med (世界中医药), 2018, 13:2559-2563.
[33] Wang J, Zhang Y, Guo L, et al. Salvianolic acid B inhibits the TLR4-NFκB-TNFα pathway and attenuates neonatal rat cardiomyocyte injury induced by lipopolysaccharide[J]. Chin J Integr Med, 2011, 17:775-779.
[34] Zhao M, Li F, Jian Y, et al. Salvianolic acid B regulates macrophage polarization in ischemic/reperfused hearts by inhibiting mTORC1-induced glycolysis[J]. Eur J Pharmacol, 2020, 871:172916.
[35] Xia Y, Zhuang H, Li Q. Cardioprotective mechanisms of salvianolic acid B pretreatment against myocardial ischemia/reperfusion injury[J]. Chin J Pharmacov (中国药物警戒), 2018, 15:644-647, 667.
[36] Hu Y, Pan YZ, Li QJ, et al. Sal B attenuates cardiomyocyte injury by regulating priming of NLRP3 inflammasomes[J]. Chin Pharmacol Bull (中国药理学通报), 2020, 36:210-215.
[37] Wang D, Wang J, Liu Y, et al. Roles of Chinese herbal medicines in ischemic heart diseases by regulating oxidative stress[J]. Int J Cardiol, 2016, 220:314-319.
[38] Ho JH, Hong CY. Salvianolic acids:small compounds with multiple mechanisms for cardiovascular protection[J]. J Biomed Sci, 2011, 18:30.
[39] Chen X, Shen N, An Y, et al. Protective effect of salvianolic acid B on cardiomyocytes of suckling rats with oxidative stress injury and its mechanism[J]. J Jilin Univ (吉林大学学报), 2018, 44:974-978.
[40] Gao F, Cun G, Ren X, et al. Protective effect of salvianolic acid B on isolated heart ischemia/reperfusion injury in rats[J]. Chin J Chin Mater Med (中国中药杂志), 2012, 37:358-361.
[41] Yang T, Lin F, Chen Y, et al. Salvianolic acid B inhibits low-density lipoprotein oxidation and neointimal hyperplasia in endothelium-denuded hypercholesterolaemic rabbits[J]. J Sci Food Agric, 2011, 91:134-141.
[42] Pei LL, Sun GC, Wang DI. Salvianolic acid B inhibits oxidative damage of bone marrow mesenchymal stem cells and promotes differentiation into cardiomyocytes[J]. Chin J Tis Eng Res (中国组织工程研究), 2021, 25:1032-1036.
[43] Guo BW, Ji YL, Miao JQ, et al. Protective effects of salvianolic acid B against t-BHP-induced vascular endothelial cell EA. hy926 injury through Keap1-Nrf2-ARE pathway[J]. Cent South Pharm (中南药学), 2020, 18:562-567.
[44] Niu Z, Xu X, Chen Y, et al. Protective effect of salvianolic acid A against isoproterenol-induced myocardial infarction in mice[J]. Chin Pharmacol Bull (中国药理学通报), 2015, 31:1667-1674.
[45] Li X, Fan J, Liu J, et al. Salvianolic acid A protects neonatal cardiomyocytes against hypoxia/reoxygenation-induced injury by preserving mitochondrial function and activating Akt/GSK-3β signals[J]. Chin J Integr Med, 2019, 25:23-30.
[46] Chen Q, Xu T, Li D, et al. JNK/PI3K/Akt signaling pathway is involved in myocardial ischemia/reperfusion injury in diabetic rats:effects of salvianolic acid A intervention[J]. Am J Transl Res, 2016, 8:2534-2548.
[47] Xu T, Wu X, Chen Q, et al. The anti-apoptotic and cardioprotective effects of salvianolic acid A on rat cardiomyocytes following ischemia/reperfusion by DUSP-mediated regulation of the ERK1/2/JNK pathway[J]. PLoS One, 2014, 9:e102292.
[48] Cui QT, Wang JH, Liu XC, et al. Salicylic acid A activates AKT/mTOR/4EBP1 pathway to relieve lipopolysaccharide-induced apoptosis and oxidative stress of H9c2 cardiomyocytes[J]. Chin J Pharmacol Toxicol (中国药理学与毒理学杂志), 2020, 34:16-23.
[49] Lin C, Liu Z, Lu Y, et al. Cardioprotective effect of salvianolic acid B on acute myocardial infarction by promoting autophagy and neovascularization and inhibiting apoptosis[J]. J Pharm Pharmacol, 2016, 68:941-952.
[50] Liu H, Liu W, Qiu H, et al. Salvianolic acid B protects against myocardial ischaemia-reperfusion injury in rats via inhibiting high mobility group box 1 protein expression through the PI3K/Akt signalling pathway[J]. Naunyn Schmiedebergs Arch Pharmacol, 2020, 393:1527-1539.
[51] Liu SS, Zang S, Tang Z, et al. Protective effect of salvianolic acid B on hypoxia-reoxygenation induced injury in H9c2 cardiomyocytes[J]. J Hunan Univ Chin Med (湖南中医药大学学报), 2017, 37:832-837.
[52] Xin GJ, Fu JH, Han X, et al. Salvianolic acid B regulates mitochondrial autophagy mediated by NIX to protect H9c2 cardiomyocytes from hypoxia/reoxygenation injury[J]. Chin J Chin Mater Med (中国中药杂志), 2020, 45:2960-2965.
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