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DOI: 10.1055/s-2007-993775
© Georg Thieme Verlag KG Stuttgart · New York
Paeonol and Paeoniflorin, the Main Active Principles of Paeonia albiflora, Protect the Heart from Myocardial Ischemia/Reperfusion Injury in Rats
Publication History
Received: June 7, 2007
Revised: November 15, 2007
Accepted: November 20, 2007
Publication Date:
17 January 2008 (online)
Abstract
The aim of this study was to investigate the effects of paeoniflorin (PF) and paeonol (PN), the main active compounds of the Paeonia albiflora Pallas, on myocardial ischemia and reperfusion (I/R)-induced injury in Sprague-Dawley rats in vivo. Under anesthesia, the rats were subjected to 25 min of ischemia by ligation of the left anterior descending coronary artery (LAD) followed by 6 h (Western blot analysis) or 24 h (hemodynamics and infarct size) of reperfusion. When the infarct size was measured as the percentage of the area at risk, both PF (25.0 % ± 7.0 %) and PN (24.1 % ± 5.5 %) significantly (P < 0.05) reduced it compared to I/R control (54.8 % ± 2.6 %). Administration of 10 mg/kg PF or PN 1 h prior to I/R injury also resulted in a significant improvement of the hemodynamic parameters. Furthermore, both PF and PN decreased the caspase-3 and Bax expressions but up-regulated Bcl-2 in the left ventricles. The results show that both PF and PN reduced myocardial damage in rat through protection from apoptosis, suggesting that Paeonia albiflora Pallas might be useful in treating myocardial infarction.
Abbreviations
AAR:area at risk
ANOVA:analysis of variance
DBP:diastolic blood pressure
HR:heart rate
ICAM:intercellular adhesion molecule
JNK:c-Jun N-terminal kinase
LAD:left anterior descending coronary artery
LV:left ventricle
LVSP:left ventricle systolic pressure
LVDP:left ventricle developed pressure
LVEDP:left ventricle end-diastolic pressure
MAP:mean arterial pressure
MAPK:mitogen-activated protein kinase
NF-κB:nuclear factor kappa B
SBP:systolic blood pressure
SDS:sodium dodecyl sulfate
PF:paeoniflorin
PN:paeonol
PVDF:polyvinylidene difluoride
TBS-T:Tris-buffered saline/Tween 20
TNF:tumor necrosis factor
VCAM:vascular cell adhesion molecule
Key words
Ischemia-reperfusion injury - apoptosis - Paeoniaceae - paeoniflorin - paeonol - Paeonia albiflora Pallas - rat
References
- 1 Ma X L, Weyrich A S, Lefer D J, Lefer A M. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res. 1993; 72 403-12
- 2 Lee Y S, Kang Y J, Kim H J, Park M K, Seo H G, Lee J H. et al . Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury. Apoptosis. 2006; 11 1091-100
- 3 Maulik N, Engelman R M, Rousou J A, Flack 3rd J E, Deaton D, Das D K. Ischemic preconditioning reduces apoptosis by upregulation anti-death gene Bcl-2. Circulation. 1999; 100 369-75
- 4 Liang J, Zhou A, Chen M, Xu S. Negatively regulatory effects of paeoniflorin on immune cells. Eur J Pharmacol. 1990; 183 901-2
- 5 Yamahara J, Yamada T, Kimura H, Sawada T, Fujimura H. Biologically active principles of crude drugs: Anti-allergic principles of ”shoseuyu-to”: I. Effect on delayed-type allergy reaction. Yakugaku Zasshi. 1982; 102 881-6
- 6 Ishida H, Takamatsu M, Tsuji K, Kosuge T. Studies on active substances in herbs used for Oketsu in Chinese medicine. VI. On the anticoagulative principle in Paeoniae Radix. Chem Pharm Bull. 1987; 35 849-52
- 7 Li C R, Zhou Z, Zhu D, Sun Y N, Dai J M, Wang S Q. Protective effect of paeoniflorin on irradiation-induced cell damage involved in modulation of reactive oxygen species and the mitogen-activated protein kinases. Int J Biochem Cell Biol. 2007; 39 426-36
- 8 Zhang G, Yu Z, Zhao H. Protective effect of paeonol on repeated cerebral ischemia in rats. Zhong Yao Cai. 1997; 20 626-8
- 9 Nizamutdinova I T, Oh H M, Min Y N, Park S H, Lee M J, Kim J S. et al . Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-α-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-κB signaling pathways. Int Immunopharmacol. 2007; 3 343-50
- 10 Kang S S, Shin K H, Chi H J. Galloylpaeoniflorin, a new acylated monoterpene glucoside from paeony root. Korean J Pharmacognosy. 1989; 20 48-9
- 11 Kang S S, Kim J S, Yun-Choi H S, Han B H. Phytochemical studies on Paeoniae radix. Korean J Pharmacognosy. 1993; 24 247-50
- 12 Kim H J, Tsoy I, Park J M, Chung J I, Shin S C, Chang K C. Anthocyanins from soybean seed coat inhibit the expression of TNF-α-induced genes associated with ischemia/reperfusion in endothelial cell by NF-κB-dependent pathway and reduce rat myocardial damage incurred by ischemia and reperfusion in vivo. FEBS Lett. 2006; 580 1391-7
- 13 Gottlieb R A, Burleson K O, Kloner R A, Babior B M, Engler R L. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 1994; 94 1621-8
- 14 Bialik S, Geenen D L, Sasson I E, Cheng R, Horner J W, Evans S M. et al . Myocytes apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. J Clin Invest. 1997; 100 1363-72
- 15 Misao J, Hayakawa Y, Ohno M, Kato S, Fujiwara T, Fujiwara H. Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation. 1996; 94 1506-12
- 16 Zhao Z Q, Nakamura M, Wang N P, Wilcox J N, Shearer S, Ronson R S. et al . Reperfusion induces myocardial apoptotic cell death. Cardiovasc Res. 2000; 45 651-60
- 17 Hsieh C L, Cheng C Y, Tsai T H, Lin I H, Liu C H, Chiang S Y. et al . Paeonol reduces cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats. J Ethnopharmacol. 2006; 106 208-15
1 These authors are equally contributed to this work
Dr. Ki Churl Chang
Department of Pharmacology
School of Medicine
Institute of Health Sciences
Gyeongsang National University
Jinju
Korea
Phone: +82-55-751-8771
Fax: +82-55-759-0609
Email: kcchang@gnu.ac.kr