Cardioprotective effects and mechanism of Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury
详细信息 查看官网全文
- 英文论文题名：Cardioprotective effects and mechanism of Radix salviae miltiorrhizae and Lignum dalbergiae odoriferae on rat myocardial ischemia/reperfusion injury
- 论文作者：Fei Mu ; JiaLin Duan ; HaiXu Bian ; Ying Yin ; YanRong Zhu ; Guo Wei ; Yue Guan ; YanHua Wang ; Chao Guo ; AiDong Wen ; Yong Yang ; MiaoMiao Xi
- 英文论文作者：Fei Mu ; JiaLin Duan ; HaiXu Bian ; Ying Yin ; YanRong Zhu ; Guo Wei ; Yue Guan ; YanHua Wang ; Chao Guo ; AiDong Wen ; Yong Yang ; MiaoMiao Xi ; Department of Pharmacy ; Xijing Hospital ; Fourth Military Medical University ; Department of Pharmacy ; Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
- 年：2016
- 作者机构：Department of Pharmacy,Xijing Hospital,Fourth Military Medical University;Department of Pharmacy,Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital;
- 英文论文关键词：Myocardial ischemia/reperfusion injury ; Radix salviae miltiorrhizae ; Lignum dalbergiae odoriferae ; The maximum and minimum effective points ; Cardioprotection ; Metabonomics
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：英文
- 分类号：R285.5
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：15
- 文件大小：2372k
- 原文格式：O
- 会议级别：全国
摘要
Objective Radix salviae miltiorrhizae(SM) and Lignum dalbergiae odoriferae(DO) are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases,but few of literature is about the systematic studies.Sprague-Dawley rats were pretreated with SM,aqueous extract of DO(DOA) and volatile oil of DO(DOO),either as monotherapy or in combination for 7 days,then subjected to 30 min of ischemia followed by 180 min of reperfusion.Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry(GC/TOF-MS) were used to identify the therapeutic effect of these traditional Chinese medicines.The results showed that SM,DOA and DOO ameliorated cardiac function respectively,and this effect was further strengthened by their combinations.Among all combinations,SM+DOO showed predominant potential(P<0.01) to improve electrocardiogram and heart rate,reduce heart weight index and myocardial infarct size,decrease the levels of CK-MB and LDH.Moreover,metabonomics-based findings such as the principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) score plot of metabolic state in rat serum correlated well to the preceding results,confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups.Furthermore,the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min.In addition,SM+DOO group markedly(P<0.01) reduced the number of TUNEL-positive cells,the levels of TNF-α,IL-6 and MDA,while increased the activity of SOD both in serum and tissue.These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats.This effect might be achieved partly through anti-apoptosis,anti-oxidant and anti-inflammatory.Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.
Objective Radix salviae miltiorrhizae(SM) and Lignum dalbergiae odoriferae(DO) are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases,but few of literature is about the systematic studies.Sprague-Dawley rats were pretreated with SM,aqueous extract of DO(DOA) and volatile oil of DO(DOO),either as monotherapy or in combination for 7 days,then subjected to 30 min of ischemia followed by 180 min of reperfusion.Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry(GC/TOF-MS) were used to identify the therapeutic effect of these traditional Chinese medicines.The results showed that SM,DOA and DOO ameliorated cardiac function respectively,and this effect was further strengthened by their combinations.Among all combinations,SM+DOO showed predominant potential(P<0.01) to improve electrocardiogram and heart rate,reduce heart weight index and myocardial infarct size,decrease the levels of CK-MB and LDH.Moreover,metabonomics-based findings such as the principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) score plot of metabolic state in rat serum correlated well to the preceding results,confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups.Furthermore,the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min.In addition,SM+DOO group markedly(P<0.01) reduced the number of TUNEL-positive cells,the levels of TNF-α,IL-6 and MDA,while increased the activity of SOD both in serum and tissue.These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats.This effect might be achieved partly through anti-apoptosis,anti-oxidant and anti-inflammatory.Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.
Objective Radix salviae miltiorrhizae(SM) and Lignum dalbergiae odoriferae(DO) are both traditional Chinese medicinal herbs for the treatment of ischemic heart disease and other cardiovascular diseases,but few of literature is about the systematic studies.Sprague-Dawley rats were pretreated with SM,aqueous extract of DO(DOA) and volatile oil of DO(DOO),either as monotherapy or in combination for 7 days,then subjected to 30 min of ischemia followed by 180 min of reperfusion.Traditional pharmacodynamic evaluation and metabonomics based on gas chromatography/time-of-flight mass spectrometry(GC/TOF-MS) were used to identify the therapeutic effect of these traditional Chinese medicines.The results showed that SM,DOA and DOO ameliorated cardiac function respectively,and this effect was further strengthened by their combinations.Among all combinations,SM+DOO showed predominant potential(P<0.01) to improve electrocardiogram and heart rate,reduce heart weight index and myocardial infarct size,decrease the levels of CK-MB and LDH.Moreover,metabonomics-based findings such as the principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) score plot of metabolic state in rat serum correlated well to the preceding results,confirming that SM+DOO exerted synergistic therapeutic efficacies to exhibit better effect on MI/R injury rats compared with other pretreatment groups.Furthermore,the maximum effective point of SM+DOO was 30 min and the minimum effective point was 180 min.In addition,SM+DOO group markedly(P<0.01) reduced the number of TUNEL-positive cells,the levels of TNF-α,IL-6 and MDA,while increased the activity of SOD both in serum and tissue.These results indicated that SM+DOO have combined effects that are highly effective than single pretreatment against MI/R injury rats.This effect might be achieved partly through anti-apoptosis,anti-oxidant and anti-inflammatory.Thus SM+DOO might be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.
引文
1.Forman MB and Jackson EK:Myocardial reperfusion injury.N Engl J Med 357:2408,2409-2410,2007.
2.Sivaraman V and Yellon DM:Pharmacologic therapy that simulates conditioning for cardiac ischemic/reperfusion injury.J Cardiovasc Pharmacol Ther 19:83-96,2014.
3.Monassier JP:Reperfusion injury in acute myocardial infarction.From bench to cath lab.Part I:Basic considerations.Arch Cardiovasc Dis 101:491-500,2008.
4.Rodriguez-Porcel M,Zhu XY and Chade AR,et al.:Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension.Am J Physiol Heart Circ Physiol 290:H978-H984,2006.
5.Liu H,Shang J and Chu F,et al.:Protective Effects of Shen-Yuan-Dan,a Traditional Chinese Medicine,against Myocardial Ischemia/Reperfusion Injury.Evidence-Based Complementary and Alternative Medicine 2013:1-11,2013.
6.Lakshmi SV,Padmaja G,Kuppusamy P and Kutala VK:Oxidative stress in cardiovascular disease.Indian J Biochem Biophys 46:421-440,2009.
7.Gottlieb RA:Cell death pathways in acute ischemia/reperfusion injury.J Cardiovasc Pharmacol Ther 16:233-238,2011.
8.Koenitzer JR and Freeman BA:Redox signaling in inflammation:interactions of endogenous electrophiles and mitochondria in cardiovascular disease.Ann Ny Acad Sci 1203:45-52,2010.
9.Li J,Zhang H and Zhang C:Role of inflammation in the regulation of coronary blood flow in ischemia and reperfusion:mechanisms and therapeutic implications.J Mol Cell Cardiol 52:865-872,2012.
10.Guan Y,Yin Y and Zhu Y,et al.:Dissection of Mechanisms of a Chinese Medicinal Formula:Danhong Injection Therapy for Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro.Evidence-Based Complementary and Alternative Medicine 2013:1-12,2013.
11.Zhao N,Liu YY and Wang F,et al.:Cardiotonic pills,a compound Chinese medicine,protects ischemia-reperfusion-induced microcirculatory disturbance and myocardial damage in rats.Am J Physiol Heart Circ Physiol 298:H1166-H1176,2010.
12.Liu Q,Li J,Wang J,Li J,Janicki JS and Fan D:Effects and mechanisms of Chinese herbal medicine in ameliorating myocardial ischemia-reperfusion injury.Evid Based Complement Alternat Med 2013:925625,2013.
13.Geng Z,Huang L,Song M and Song Y:Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol(ISO)-induced myocardial injury in rats.Carbohyd Polym 132:638-642,2015.
14.Sugiyama A,Zhu BM,Takahara A,Satoh Y and Hashimoto K:Cardiac effects of salvia miltiorrhiza/dalbergia odorifera mixture,an intravenously applicable Chinese medicine widely used for patients with ischemic heart disease in China.Circ J 66:182-184,2002.
15.Zhao L,Gao H,Zhao Y and Lin D:Metabonomic analysis of the therapeutic effect of Zhibai Dihuang Pill in treatment of streptozotocin-induced diabetic nephropathy.J Ethnopharmacol 142:647-656,2012.
16.Liu P and Wang P:Application of metabolomics technology in the research of Chinese medicine.Chinese Journal of Integrative Medicine 20:307-310,2014.
17.Chen M,Su M and Zhao L,et al.:Metabonomic study of aristolochic acid-induced nephrotoxicity in rats.J Proteome Res 5:995-1002,2006.
18.Griffin JL and Bollard ME:Metabonomics:its potential as a tool in toxicology for safety assessment and data integration.Curr Drug Metab 5:389-398,2004.
19.Yin P,Zhao X,Li Q,Wang J,Li J and Xu G:Metabonomics study of intestinal fistulas based on ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry(UPLC/Q-TOF MS).J Proteome Res 5:2135-2143,2006.
20.Ganna A,Salihovic S and Sundstrom J,et al.:Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease.PLoS Genet 10:e1004801,2014.
21.Luo L,Zhen L and Xu Y,et al.:1H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.J Ethnopharmacol 186:257-269,2016.
22.Chang KL and Ho PC:Gas Chromatography Time-Of-Flight Mass Spectrometry(GC-TOF-MS)-Based Metabolomics for Comparison of Caffeinated and Decaffeinated Coffee and Its Implications for Alzheimer's Disease.PLoS ONE 9:e104621,2014.
23.Klein J,Papadopoulos T,Mischak H and Mullen W:Comparison of CE-MS/MS and LC-MS/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine.Electrophoresis 35:1060-1064,2014.
24.Tang YM,Wang JP and Bao WM,et al.:Urine and serum metabolomic profiling reveals that bile acids and carnitine may be potential biomarkers of primary biliary cirrhosis.Int J Mol Med 36:377-385,2015.
25.Koek MM,Muilwijk B,van der Werf MJ and Hankemeier T:Microbial metabolomics with gas chromatography/mass spectrometry.Anal Chem 78:1272-1281,2006.
26.Yin Y,Guan Y and Duan J,et al.:Cardioprotective effect of Danshensu against myocardial ischemia/reperfusion injury and inhibits apoptosis of H9c2 cardiomyocytes via Akt and ERK1/2 phosphorylation.Eur J Pharmacol 699:219-226,2013.
27.Zheng X,Zhao X,Wang S,Luo K,Wei Y and Zheng J:Co-administration of Dalbergia odorifera increased bioavailability of Salvia miltiorrhizae in rabbits.Am J Chin Med 35:831-840,2007.
28.Quan W,Wei G and Zhou D,et al.:Magnesium lithospermate B reduces myocardial ischemia/reperfusion injury in rats.Pharm Biol 51:1355-1362,2013.
29.Deng Y,Yang M and Xu F,et al.:Combined Salvianolic Acid B and Ginsenoside Rgl Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats.PLOS ONE 10:el35435,2015.
30.Arya DS,Bansal P,Ojha SK,Nandave M,Mohanty I and Gupta SK:Pyruvate provides cardioprotection in the experimental model of myocardial ischemic reperfusion injury.Life Sci 79:38-44,2006.
31.Kemp M,Donovan J,Higham H and Hooper J:Biochemical markers of myocardial injury.Br J Anaesth 93:63-73,2004.
32.Yan J,Duan J and Wu X,et al.:Total saponins from Aralia taibaiensis protect against myocardial ischemia/reperfusion injury through AMPK pathway.Int J Mol Med 36:1538-1546,2015.
33.Tao Z,Chen B and Tan X,et al.:Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction(MI)heart.Proc Natl Acad Sci U S A 108:2064-2069,2011.
34.Kung G,Konstantinidis K and Kitsis RN:Programmed Necrosis,Not Apoptosis,in the Heart.Circ Res:1017-1036,2011.
35.Garciarena CD,Fantinelli JC and Caldiz CI,et al.:Myocardial reperfusion injury:reactive oxygen species vs.NHE-1reactivation.Cell Physiol Biochem 27:13-22,2011.
36.Jaeschke H and Woolbright BL:Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species.Transplantation Reviews 26:103-114,2012.
37.Zheng W,Huang LZ and Zhao L,et al.:Superoxide dismutase activity and malondialdehyde level in plasma and morphological evaluation of acute severe hemorrhagic shock in rats.Am J Emerg Med 26:54-58,2008.
38.Schettler V,Methe H,Staschinsky D,Schuff-Werner P,Muller GA and Wieland E:Review:the oxidant/antioxidant balance during regular low density lipoprotein apheresis.Ther Apher 3:219-226,1999.
39.Willerson JT:Inflammation as a Cardiovascular Risk Factor.Circulation 109:2-10,2004.
40.Gasparyan AY:Cardiovascular risk and inflammation:pathophysiological mechanisms,drug design,and targets.Curr Pharm Des 18:1447-1449,2012.
41.Song F,Li H,Sun J and Wang S:Protective effects of cinnamic acid and cinnamic aldehyde on isoproterenol-induced acute myocardial ischemia in rats.J Ethnopharmacol 150:125-130,2013.
42.Yan B,Deng Y and Hou J,et al.:UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet.Molecular BioSystems:486-496,2015.
2.Sivaraman V and Yellon DM:Pharmacologic therapy that simulates conditioning for cardiac ischemic/reperfusion injury.J Cardiovasc Pharmacol Ther 19:83-96,2014.
3.Monassier JP:Reperfusion injury in acute myocardial infarction.From bench to cath lab.Part I:Basic considerations.Arch Cardiovasc Dis 101:491-500,2008.
4.Rodriguez-Porcel M,Zhu XY and Chade AR,et al.:Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension.Am J Physiol Heart Circ Physiol 290:H978-H984,2006.
5.Liu H,Shang J and Chu F,et al.:Protective Effects of Shen-Yuan-Dan,a Traditional Chinese Medicine,against Myocardial Ischemia/Reperfusion Injury.Evidence-Based Complementary and Alternative Medicine 2013:1-11,2013.
6.Lakshmi SV,Padmaja G,Kuppusamy P and Kutala VK:Oxidative stress in cardiovascular disease.Indian J Biochem Biophys 46:421-440,2009.
7.Gottlieb RA:Cell death pathways in acute ischemia/reperfusion injury.J Cardiovasc Pharmacol Ther 16:233-238,2011.
8.Koenitzer JR and Freeman BA:Redox signaling in inflammation:interactions of endogenous electrophiles and mitochondria in cardiovascular disease.Ann Ny Acad Sci 1203:45-52,2010.
9.Li J,Zhang H and Zhang C:Role of inflammation in the regulation of coronary blood flow in ischemia and reperfusion:mechanisms and therapeutic implications.J Mol Cell Cardiol 52:865-872,2012.
10.Guan Y,Yin Y and Zhu Y,et al.:Dissection of Mechanisms of a Chinese Medicinal Formula:Danhong Injection Therapy for Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro.Evidence-Based Complementary and Alternative Medicine 2013:1-12,2013.
11.Zhao N,Liu YY and Wang F,et al.:Cardiotonic pills,a compound Chinese medicine,protects ischemia-reperfusion-induced microcirculatory disturbance and myocardial damage in rats.Am J Physiol Heart Circ Physiol 298:H1166-H1176,2010.
12.Liu Q,Li J,Wang J,Li J,Janicki JS and Fan D:Effects and mechanisms of Chinese herbal medicine in ameliorating myocardial ischemia-reperfusion injury.Evid Based Complement Alternat Med 2013:925625,2013.
13.Geng Z,Huang L,Song M and Song Y:Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol(ISO)-induced myocardial injury in rats.Carbohyd Polym 132:638-642,2015.
14.Sugiyama A,Zhu BM,Takahara A,Satoh Y and Hashimoto K:Cardiac effects of salvia miltiorrhiza/dalbergia odorifera mixture,an intravenously applicable Chinese medicine widely used for patients with ischemic heart disease in China.Circ J 66:182-184,2002.
15.Zhao L,Gao H,Zhao Y and Lin D:Metabonomic analysis of the therapeutic effect of Zhibai Dihuang Pill in treatment of streptozotocin-induced diabetic nephropathy.J Ethnopharmacol 142:647-656,2012.
16.Liu P and Wang P:Application of metabolomics technology in the research of Chinese medicine.Chinese Journal of Integrative Medicine 20:307-310,2014.
17.Chen M,Su M and Zhao L,et al.:Metabonomic study of aristolochic acid-induced nephrotoxicity in rats.J Proteome Res 5:995-1002,2006.
18.Griffin JL and Bollard ME:Metabonomics:its potential as a tool in toxicology for safety assessment and data integration.Curr Drug Metab 5:389-398,2004.
19.Yin P,Zhao X,Li Q,Wang J,Li J and Xu G:Metabonomics study of intestinal fistulas based on ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry(UPLC/Q-TOF MS).J Proteome Res 5:2135-2143,2006.
20.Ganna A,Salihovic S and Sundstrom J,et al.:Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease.PLoS Genet 10:e1004801,2014.
21.Luo L,Zhen L and Xu Y,et al.:1H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.J Ethnopharmacol 186:257-269,2016.
22.Chang KL and Ho PC:Gas Chromatography Time-Of-Flight Mass Spectrometry(GC-TOF-MS)-Based Metabolomics for Comparison of Caffeinated and Decaffeinated Coffee and Its Implications for Alzheimer's Disease.PLoS ONE 9:e104621,2014.
23.Klein J,Papadopoulos T,Mischak H and Mullen W:Comparison of CE-MS/MS and LC-MS/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine.Electrophoresis 35:1060-1064,2014.
24.Tang YM,Wang JP and Bao WM,et al.:Urine and serum metabolomic profiling reveals that bile acids and carnitine may be potential biomarkers of primary biliary cirrhosis.Int J Mol Med 36:377-385,2015.
25.Koek MM,Muilwijk B,van der Werf MJ and Hankemeier T:Microbial metabolomics with gas chromatography/mass spectrometry.Anal Chem 78:1272-1281,2006.
26.Yin Y,Guan Y and Duan J,et al.:Cardioprotective effect of Danshensu against myocardial ischemia/reperfusion injury and inhibits apoptosis of H9c2 cardiomyocytes via Akt and ERK1/2 phosphorylation.Eur J Pharmacol 699:219-226,2013.
27.Zheng X,Zhao X,Wang S,Luo K,Wei Y and Zheng J:Co-administration of Dalbergia odorifera increased bioavailability of Salvia miltiorrhizae in rabbits.Am J Chin Med 35:831-840,2007.
28.Quan W,Wei G and Zhou D,et al.:Magnesium lithospermate B reduces myocardial ischemia/reperfusion injury in rats.Pharm Biol 51:1355-1362,2013.
29.Deng Y,Yang M and Xu F,et al.:Combined Salvianolic Acid B and Ginsenoside Rgl Exerts Cardioprotection against Ischemia/Reperfusion Injury in Rats.PLOS ONE 10:el35435,2015.
30.Arya DS,Bansal P,Ojha SK,Nandave M,Mohanty I and Gupta SK:Pyruvate provides cardioprotection in the experimental model of myocardial ischemic reperfusion injury.Life Sci 79:38-44,2006.
31.Kemp M,Donovan J,Higham H and Hooper J:Biochemical markers of myocardial injury.Br J Anaesth 93:63-73,2004.
32.Yan J,Duan J and Wu X,et al.:Total saponins from Aralia taibaiensis protect against myocardial ischemia/reperfusion injury through AMPK pathway.Int J Mol Med 36:1538-1546,2015.
33.Tao Z,Chen B and Tan X,et al.:Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction(MI)heart.Proc Natl Acad Sci U S A 108:2064-2069,2011.
34.Kung G,Konstantinidis K and Kitsis RN:Programmed Necrosis,Not Apoptosis,in the Heart.Circ Res:1017-1036,2011.
35.Garciarena CD,Fantinelli JC and Caldiz CI,et al.:Myocardial reperfusion injury:reactive oxygen species vs.NHE-1reactivation.Cell Physiol Biochem 27:13-22,2011.
36.Jaeschke H and Woolbright BL:Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species.Transplantation Reviews 26:103-114,2012.
37.Zheng W,Huang LZ and Zhao L,et al.:Superoxide dismutase activity and malondialdehyde level in plasma and morphological evaluation of acute severe hemorrhagic shock in rats.Am J Emerg Med 26:54-58,2008.
38.Schettler V,Methe H,Staschinsky D,Schuff-Werner P,Muller GA and Wieland E:Review:the oxidant/antioxidant balance during regular low density lipoprotein apheresis.Ther Apher 3:219-226,1999.
39.Willerson JT:Inflammation as a Cardiovascular Risk Factor.Circulation 109:2-10,2004.
40.Gasparyan AY:Cardiovascular risk and inflammation:pathophysiological mechanisms,drug design,and targets.Curr Pharm Des 18:1447-1449,2012.
41.Song F,Li H,Sun J and Wang S:Protective effects of cinnamic acid and cinnamic aldehyde on isoproterenol-induced acute myocardial ischemia in rats.J Ethnopharmacol 150:125-130,2013.
42.Yan B,Deng Y and Hou J,et al.:UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet.Molecular BioSystems:486-496,2015.