Paeonol Attenuates High-Fat-Diet-Induced Atherosclerosis in Rabbits by Anti-Inflammatory Activity

Abstract

Cortex Moutan (Paeonia suffruticosa Andrews, Ranunculaceae) has several uses in traditional medicine, such as analgesic, antipyretic, and anti-inflammatory applications and use in the prevention of thromboembolic diseases. Paeonol, a main active component in Cortex Moutan, possesses various pharmacological activities, particularly an anti-atherosclerosis effect. However, so far there have been no reports evaluating the anti-inflammatory action of paeonol in atherosclerosis therapy. The purpose of this study was to investigate the association of the therapeutic effect of paeonol on atherosclerotic rabbits with its anti-inflammatory action. The atherosclerotic model was developed in 24 rabbits fed a high-fat diet for 12 weeks. Twelve rabbits on the high-fat diet then were administered with paeonol (p.o) for a subsequent 6 weeks at the doses of 75 mg/kg and 150 mg/kg. Histological analysis showed significant improvement in atherosclerosis plaque in the paeonol groups. Moreover, the blood levels of TNF-α, IL-1β, and CRP and the translocation of NF-κB to the nucleus were significantly suppressed in paeonol groups, as was the inhibition of lipid peroxidation. In conclusion, these findings suggest that the anti-inflammatory action of paeonol may contribute to its anti-atherosclerosis effect.

Key words

paeonol - Cortex Moutan - Paeonia suffruticosa Andrews (Ranunculaceae) - atherosclerosis - proinflammatory cytokine - NF-kB

References

• 1 Chou T C. Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia.  Br J Pharmacol. 2003;  139 1146-52
• 2 Zhang L H, Xiao P G, Huang Y. Recent progresses in pharmacological and clinical studies of paeonol.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 1996;  16 187-90
• 3 Lin H C, Ding H Y, Ko F N, Teng C M, Wu Y C. Aggregation inhibitory activity of minor acetophenones from Paeonia species.  Planta Med. 1999;  65 595-9
• 4 Nizamutdinova I T, Jin Y C, Kim J S, Yean M H, Kang S S, Kim Y S. et al . Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats.  Planta Med. 2008;  74 14-8
• 5 Riley C M, Ren T C. Simple method for the determination of paeonol in human and rabbit plasma by high-performance liquid chromatography using solid-phase extraction and ultraviolet detection.  J Chromatogr. 1989;  489 432-7
• 6 Zhang H Y, Ge N, Zhang Z Y. Theoretical elucidation of activity differences of five phenolic antioxidants.  Zhongguo Yao Li Xue Bao. 1999;  20 363-6
• 7 Sun Y C, Shen Y X, GP S. Advances in the studies of major pharmacological activity of paeonol.  Chin Tradit Pat Med. 2004;  26 579-82
• 8 Shi L, Fan P S, Fang J X, Han Z X. Inhibitory effects of paeonol on experimental atherosclerosis and platelet aggregation of rabbit.  Acta Pharmacolog Sin. 1988;  9 555-8
• 9 Dai M, Zhi X, Peng D, Liu Q. Inhibitory effect of paeonol on experimental atherosclerosis in quails.  China J Chin Mater Med. 1999;  24 488-90
• 10 Hansson G K. Inflammation, atherosclerosis, and coronary artery disease.  N Engl J Med. 2005;  352 1685-95
• 11 Hirai A, Terano T, Hamazaki T, Sajiki J, Saito H, Tahara K. et al . Studies on the mechanism of antiaggregatory effect of Moutan Cortex.  Thromb Res. 1983;  31 29-40
• 12 Ross R. Atherosclerosis-an inflammatory disease.  N Engl J Med. 1999;  340 115-26
• 13 Liuzzo G, Biasucci L M, Gallimore J R, Grillo R L, Rebuzzi A G, Pepys M B. et al . The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina.  N Engl J Med. 1994;  331 417-24
• 14 Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease.  N Engl J Med. 2000;  343 1139-47
• 15 Aguilera C M, Ramirez-Tortosa M C, Mesa M D, Ramirez-Tortosa C L, Gil A. Sunflower, virgin-olive and fish oils differentially affect the progression of aortic lesions in rabbits with experimental atherosclerosis.  Atherosclerosis. 2002;  162 335-44
• 16 Rikitake Y, Hirata K, Kawashima S, Akita H, Yokoyama M. Inhibitory effect of inducible type nitric oxide synthase on oxidative modification of low density lipoprotein by vascular smooth muscle cells.  Atherosclerosis. 1998;  136 51-7
• 17 Chen M J, Wu Y C, Wu Q, Yang Y, Yang F, MZ C. Effect of liver-aid tabliets on NF-κB expression in rat hepatic fibrosis.  Chin J Histochem Cytochem. 2005;  14 410-4
• 18 Lucas A R, Korol R, Pepine C J. Inflammation in atherosclerosis: some thoughts about acute coronary syndromes.  Circulation. 2006;  113 e728-32
• 19 Huang H, Chang E J, Lee Y, Kim J S, Kang S S, Kim H H. A genome-wide microarray analysis reveals anti-inflammatory target genes of paeonol in macrophages.  Inflamm Res. 2008;  57 189-98
• 20 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-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways.  Int Immunopharmacol. 2007;  7 343-50
• 21 Wilson S H, Best P J, Edwards W D, Holmes DR J r, Carlson P J, Celermajer D S. et al . Nuclear factor-kappaB immunoreactivity is present in human coronary plaque and enhanced in patients with unstable angina pectoris.  Atherosclerosis. 2002;  160 147-53
• 22 Wilson S H, Caplice N M, Simari R D, Holmes DR J r, Carlson P J, Lerman A. Activated nuclear factor-kappaB is present in the coronary vasculature in experimental hypercholesterolemia.  Atherosclerosis. 2000;  148 23-30
• 23 Lindroos P M, Rice A B, Wang Y Z, Bonner J C. Role of nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways in IL-1 beta-mediated induction of alpha-PDGF receptor expression in rat pulmonary myofibroblasts.  J Immunol. 1998;  161 3464-8
• 24 Novitskiy G, Ravi R, Potter J J, Rennie-Tankersley L, Wang L, Mezey E. Effects of acetaldehyde and TNF alpha on the inhibitory kappa B-alpha protein and nuclear factor kappa B activation in hepatic stellate cells.  Alcohol. 2005;  40 96-101
• 25 Morello S, Ito K, Yamamura S, Lee K Y, Jazrawi E, Desouza P. et al . IL-1 beta and TNF-alpha regulation of the adenosine receptor (A2A) expression: differential requirement for NF-kappa B binding to the proximal promoter.  J Immunol. 2006;  177 7173-83
• 26 Pradhan A D, Manson J E, Rossouw J E, Siscovick D S, Mouton C P, Rifai N. et al . Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative observational study.  Jama. 2002;  288 980-7
• 27 Ridker P M, Rifai N, Rose L, Buring J E, Cook N R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.  N Engl J Med. 2002;  347 1557-65