期刊论文详细信息
BMC Complementary and Alternative Medicine
The cardioprotective effect of danshen and gegen decoction on rat hearts and cardiomyocytes with post-ischemia reperfusion injury
Kwok-Pui Fung1  Kit-Man Lau3  Judy Yuet-Wa Chan3  Chi-Man Koon3  Fan Hu2 
[1] 509A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China;School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
关键词: Calcium;    Apoptosis;    Hypoxia and reoxygenation;    Ischemia and reperfusion;    Danshen and Gegen decoction;   
Others  :  1231417
DOI  :  10.1186/1472-6882-12-249
 received in 2012-03-26, accepted in 2012-11-30,  发布年份 2012
PDF
【 摘 要 】

Background

Danshen (Salviae Miltiorrhizae Radix) and Gegen (Puerariae Lobatae Radix) have been used for treating heart disease for several thousand years in China. It has been found that a Danshen and Gegen decoction (DG) exhibiting an anti-atherosclerosis effect, which improves the patients’ heart function recovery. Pre-treatment with DG was reported to have protective effects on myocardium against ischemia/reperfusion injury. In the present study, we aim to investigate the post-treatment effect of DG on ischemic-reperfusion injuries ex vivo or in vitro and the underlying mechanisms involved.

Methods

The rat heart function in an ischemia and reperfusion (I/R) model was explored by examining three parameters including contractile force, coronary flow rate and the release of heart specific enzymes within the heart perfusate. In vitro model of hypoxia and reoxygenation (H/R), the protective effect of DG on damaged cardiomyocytes was investigated by examining the cell structure integrity, the apoptosis and the functionality of mitochondria.

Results

Our results showed that DG significantly improved rat heart function after I/R challenge and suppressed the release of enzymes by damaged heart muscles in a dose-dependent manner. DG also significantly inhibited the death of cardiomyocytes, H9c2 cells, with a H/R challenge. It obviously decreased cell apoptosis, protected the mitochondrial function and cell membrane skeleton integrity on H9c2 cells. The cardio-protection was also found to be related to a decrease in intracellular calcium accumulation within H9c2 cells after I/R challenge.

Conclusion

The potential application of DG in treating rat hearts with an I/R injury has been implied in this study. Our results suggested that DG decoction could act as an anti-apoptotic and anti-ion stunning agent to protect hearts against an I/R injury.

【 授权许可】

   
2012 Hu et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20151109141215256.pdf 2534KB PDF download
Figure 7. 248KB Image download
Figure 6. 71KB Image download
Figure 5. 72KB Image download
Figure 4. 88KB Image download
Figure 3. 35KB Image download
Figure 2. 24KB Image download
Figure 1. 80KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】
  • [1]Levick JR: An introduction to cardiovascular physiology. Fourth edn edition. London, UK: Oxford University Press Inc; 2003.
  • [2]Bers DM: Excitation-contraction coupling and cardiac contractile force. Dordrecht: Kluwer; 2001.
  • [3]Chien KR, Han A, Sen A, Buja LM, Willerson JT: Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids. Circ Res 1984, 54(3):313-322.
  • [4]Shug AL, Thomsen JH, Folts JD, Bittar N, Klein MI, Koke JR, Huth PJ: Changes in tissue levels of carnitine and other metabolites during myocardial ischemia and anoxia. Arch Biochem Biophys 1978, 187(1):25-33.
  • [5]Akabas MH: Na+/Ca2+ exchange inhibitors: potential drugs to mitigate the severity of ischemic injury. Mol Pharmacol 2004, 66(1):8-10.
  • [6]Pierce GN, Czubryt MP: The contribution of ionic imbalance to ischemia/reperfusion-induced injury. J Mol Cell Cardiol 1995, 27(1):53-63.
  • [7]Schafer C, Ladilov Y, Inserte J, Schafer M, Haffner S, Garcia-Dorado D, Piper HM: Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury. Cardiovasc Res 2001, 51(2):241-250.
  • [8]Lewandrowski K, Chen A, Januzzi J: Cardiac markers for myocardial infarction. A brief review. Am J Clin Pathol 2002, 118(Suppl):S93-S99.
  • [9]Bocalini DS, Santos L, Antonio EL, Santos AA, Davel AP, Rossoni LV, Vassalo DV, Tucci PJ: Myocardial remodeling after large infarcts in rat converts post rest-potentiation in force decay. Arq Bras Cardiol 2012, 98(3):243-251.
  • [10]Mohan IK, Khan M, Wisel S, Selvendiran K, Sridhar A, Carnes CA, Bognar B, Kalai T, Hideg K, Kuppusamy P: Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction. Am J Physiol Heart Circ Physiol 2009, 296(1):H140-H151.
  • [11]Lefer DJ, Granger DN: Oxidative stress and cardiac disease. Am J Med 2000, 109(4):315-323.
  • [12]Hoffman JW Jr, Gilbert TB, Poston RS, Silldorff EP: Myocardial reperfusion injury: etiology, mechanisms, and therapies. J Extra Corpor Technol 2004, 36(4):391-411.
  • [13]Murphy E, Steenbergen C: Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 2008, 88(2):581-609.
  • [14]Zucchi R, Ghelardoni S, Evangelista S: Biochemical basis of ischemic heart injury and of cardioprotective interventions. Curr Med Chem 2007, 14(15):1619-1637.
  • [15]Zweier JL, Talukder MA: The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006, 70(2):181-190.
  • [16]Zorov DB, Juhaszova M, Sollott SJ: Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta 2006, 1757(5–6):509-517.
  • [17]Huang T, Shi C: Zhong yao fang ji xian dai yan jiu da dian. 1st edition. Beijing: Ke xue chu ban she; 1996.
  • [18]Chan K, Chui SH, Wong DY, Ha WY, Chan CL, Wong RN: Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction. Life Sci 2004, 75(26):3157-3171.
  • [19]Kamata K, Iizuka T, Nagai M, Kasuya Y: Endothelium-dependent vasodilator effects of the extract from Salviae Miltiorrhizae radix. A study on the identification of lithospermic acid B in the extracts. Gen Pharmacol 1993, 24(4):977-981.
  • [20]Liu GT, Zhang TM, Wang BE, Wang YW: Protective action of seven natural phenolic compounds against peroxidative damage to biomembranes. Biochem Pharmacol 1992, 43(2):147-152.
  • [21]Ji XY, Tan BKH, Zhu YC, Linz W, Zhu YZ: Comparison of cardioprotective effects using ramipril and DanShen for the treatment of acute myocardial infarction in rats. Life Sci 2003, 73(11):1413-1426.
  • [22]Sun J, Huang SH, Tan BK, Whiteman M, Zhu YC, Wu YJ, Ng Y, Duan W, Zhu YZ: Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction. Life Sci 2005, 76(24):2849-2860.
  • [23]Zhao BL, Jiang W, Zhao Y, Hou JW, Xin WJ: Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. Biochem Mol Biol Int 1996, 38(6):1171-1182.
  • [24]Cao ZL, Li JP, Zhang DM: Advances in the studies of isflavonoids in medicinal plants of Pueraria species. Zhong Yao Cai 2005, 28:67-71.
  • [25]Li G, Zhang Q, Wang Y: Chemical constituents from roots of Pueraria lobata. Zhongguo Zhong Yao Za Zhi 2010, 35(23):3156-3160.
  • [26]Choo MK, Park EK, Yoon HK, Kim DH: Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora. Biol Pharm Bull 2002, 25(10):1328-1332.
  • [27]Hintz KK, Ren J: Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity-induced cardiac contractile dysfunction in ventricular myocytes. Endocr Res 2004, 30(2):215-223.
  • [28]Yan LP, Chan SW, Chan AS, Chen SL, Ma XJ, Xu HX: Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats. Life Sci 2006, 79(4):324-330.
  • [29]Tam WY, Chook P, Qiao M, Chan LT, Chan TYK, Poon YK, Fung KP, Leung PC, Woo KS: The efficacy and tolerability of adjunctive alternative herbal medicine (salvia miltiorrhiza and pueraria lobata) on vascular function and structure in coronary patients. J Altern Complem Med 2009, 15(4):415-421.
  • [30]Koon CM, Woo KS, Leung PC, Fung KP: Salviae miltiorrhizae radix and puerariae lobatae radix herbal formula mediates anti-atherosclerosis by modulating key atherogenic events both in vascular smooth muscle cells and endothelial cells. J Ethnopharmacol 2011, 138(1):175-183.
  • [31]Chiu PY, Wong SM, Leung HY, Leong PK, Chen N, Zhou LM, Zuo Z, Lam PY, Ko KM: Long-term treatment with danshen-gegen decoction protects the myocardium against ischemia/reperfusion injury via the redox-sensitive protein kinase C-epsilon/mK(ATP) pathway in rats. Rejuv Res 2011, 14(2):173-184.
  • [32]Chiu PY, Wong SM, Leung HY, Leong PK, Chen N, Zhou LM, Zuo Z, Lam PY, Ko KM: Acute treatment with Danshen-Gegen decoction protects the myocardium against ischemia/reperfusion injury via the redox-sensitive PKC epsilon/mK(ATP) pathway in rats. Phytomedicine 2011, 18(11):916-925.
  • [33]Lam FF, Deng SY, Ng ES, Yeung JH, Kwan YW, Lau CB, Koon JC, Zhou L, Zuo Z, Leung PC, et al.: Mechanisms of the relaxant effect of a danshen and gegen formulation on rat isolated cerebral basilar artery. J Ethnopharmacol 2010, 132(1):186-192.
  • [34]Sagach VF, Scrosati M, Fielding J, Rossoni G, Galli C, Visioli F: The water-soluble vitamin E analogue Trolox protects against ischaemia/reperfusion damage in vitro and ex vivo. A comparison with vitamin E. Pharmacol Res 2002, 45(6):435-439.
  • [35]Chang WT, Shao ZH, Yin JJ, Mehendale S, Wang CZ, Qin Y, Li J, Chen WJ, Chien CT, Becker LB, et al.: Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes. Eur J Pharmacol 2007, 566(1–3):58-66.
  • [36]Budinger GR, Duranteau J, Chandel NS, Schumacker PT: Hibernation during hypoxia in cardiomyocytes. Role of mitochondria as the O2 sensor. J Biol Chem 1998, 273(6):3320-3326.
  • [37]Sieveking DP, Woo KS, Fung KP, Lundman P, Nakhla S, Celermajer DS: Chinese herbs Danshen and Gegen modulate key early atherogenic events in vitro. Int J Cardiol 2005, 105(1):40-45.
  • [38]Ng CF, Koon CM, Cheung DW, Lam MY, Leung PC, Lau CB, Fung KP: The anti-hypertensive effect of Danshen (Salvia miltiorrhiza) and Gegen (Pueraria lobata) formula in rats and its underlying mechanisms of vasorelaxation. J Ethnopharmacol 2011, 137(3):1366-1372.
  • [39]Wagner H, Bauer R, Melchart D, Xiao PG, Staudinger A: Chromatographic fingerprint analysis of herbal medicines. 2nd edition. Springer Wien New York; 2011:903-921.
  • [40]Acierno LJ: Adolph Fick: mathematician, physicist, physiologist. Clin Cardiol 2000, 23(5):390-391.
  • [41]Hensley K, Robinson KA, Gabbita SP, Salsman S, Floyd RA: Reactive oxygen species, cell signaling, and cell injury. Free Radic Biol Med 2000, 28(10):1456-1462.
  • [42]Tanasijevic MJ, Cannon CP, Wybenga DR, Fischer GA, Grudzien C, Gibson CM, Winkelman JW, Antman EM, Braunwald E: Myoglobin, creatine kinase MB, and cardiac troponin-I to assess reperfusion after thrombolysis for acute myocardial infarction: results from TIMI 10A. Am Heart J 1997, 134(4):622-630.
  • [43]Loor G, Kondapalli J, Iwase H, Chandel NS, Waypa GB, Guzy RD, Vanden Hoek TL, Schumacker PT: Mitochondrial oxidant stress triggers cell death in simulated ischemia-reperfusion. Biochim Biophys Acta 2011, 1813(7):1382-1394.
  • [44]Aon MA, Cortassa S, O’Rourke B: Mitochondrial oscillations in physiology and pathophysiology. Adv Exp Med Biol 2008, 641:98-117.
  • [45]Akar FG, Aon MA, Tomaselli GF, O’Rourke B: The mitochondrial origin of postischemic arrhythmias. J Clin Invest 2005, 115(12):3527-3535.
  • [46]Honda HM, Ping P: Mitochondrial permeability transition in cardiac cell injury and death. Cardiovasc Drugs Ther 2006, 20(6):425-432.
  • [47]Buki A, Okonkwo DO, Wang KK, Povlishock JT: Cytochrome c release and caspase activation in traumatic axonal injury. J Neurosci 2000, 20(8):2825-2834.
  • [48]Hu Y, Benedict MA, Ding L, Nunez G: Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J 1999, 18(13):3586-3595.
  • [49]Liu X, Kim CN, Yang J, Jemmerson R, Wang X: Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996, 86(1):147-157.
  • [50]Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu SS: Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am J Physiol Cell Physiol 2004, 287(4):C817-C833.
  • [51]Dixon IM, Hata T, Dhalla NS: Sarcolemmal Na(+)-K(+)-ATPase activity in congestive heart failure due to myocardial infarction. Am J Physiol 1992, 262(3 Pt 1):C664-C671.
  • [52]Dixon IM, Kaneko M, Hata T, Panagia V, Dhalla NS: Alterations in cardiac membrane Ca2+ transport during oxidative stress. Mol Cell Biochem 1990, 99(2):125-133.
  • [53]Cao CM, Xia Q, Zhang X, Xu WH, Jiang HD, Chen JZ: Salvia miltiorrhiza attenuates the changes in contraction and intracellular calcium induced by anoxia and reoxygenation in rat cardiomyocytes. Life Sci 2003, 72(22):2451-2463.
  • [54]Liu YH, Yang XP, Nass O, Sabbah HN, Peterson E, Carretero OA: Chronic heart failure induced by coronary artery ligation in Lewis inbred rats. Am J Physiol 1997, 272:H722-H727.
  文献评价指标  
  下载次数:26次 浏览次数:10次