Suppression of low-density lipoprotein oxidation, vascular smooth muscle cell proliferation and migration by a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii

BMC Complementary and Alternative Medicine

Kwok-Pui Fung²  Chun-Tao Che³  Ping-Chung Leung¹  Johnny C Koon¹  Judy Y Chan² 

[1] State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China;School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China;Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China

关键词: migration;    proliferation;    vascular smooth muscle cell;    Atherosclerosis;   

Others  :  1233644
DOI  :  10.1186/1472-6882-11-32

 received in 2010-08-25, accepted in 2011-04-22,  发布年份 2011

【 摘 要 】

Background

Atherosclerosis is a major cause of death in developed world. Atherosclerosis is characterized by low-density lipoprotein deposition in the arterial wall which ultimately begets the formation of lesions. Rupture of lesions finally leads to clinical events such as heart attack and stroke. Atherosclerosis is a complication associated with diabetes. In patients with diabetes, the risk of atherosclerosis is three to five folds greater than in non-diabetics. Our previous study showed that a herbal extract of Radix Astragali, Radix Codonopsis and Cortex Lycii, namely SR10, could improve glucose homeostasis both in vitro and in vivo. In this study, we want to further investigate the efficacy of SR10 in treating atherosclerosis.

Method

The inhibitory effect of SR10 on low-density lipoprotein oxidation was investigated using free radical-induced erythrocyte hemolysis model and copper ion-induced low-density lipoprotein oxidation model. Since vascular smooth muscle cell proliferation and migration are important processes in atherogenesis, we also examined the effect of SR10 in inhibiting these events.

Results

Our results showed that SR10 inhibited erythrocyte hemolysis with IC₅₀ value at 0.25 mg/ml and significantly prolonged low-density lipoprotein oxidation in vitro. SR10 attenuated platelet derived growth factor-BB-induced vascular smooth muscle cell proliferation by promoting cell cycle arrest at G₀/G₁ phase as well as inhibiting vascular smooth muscle cell migration.

Conclusion

The potential application of SR10 in treating atherosclerosis has been implied in this study. Animal model will be needed to further verify the efficacy of SR10 in future.

【 授权许可】

   
2011 Chan et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Albright A: What is public health practice telling us about diabetes? J Am Diet Assoc 2008, 108:S12-8.
• [2]Bessesen DH: Update on obesity. J Clin Endocrinol Metab 2008, 93:2027-2034.
• [3]Vergès B: New insight into the pathophysiology of lipid abnormalities in type 2 diabetes. Diabetes Metab 2005, 31:429-439.
• [4]Krentz AJ: Lipoprotein abnormalities and their consequences for patients with type 2 diabetes. Diabetes Obes Metab 2003, 5:S19-27.
• [5]Stewart CR, Tseng AA, Mok YF, Staples MK, Schiesser CH, Lawrence LJ, Varghese JN, Moore KJ, Howlett GJ: Oxidation of low-density lipoproteins induces amyloid-like structures that are recognized by macrophages. Biochemistry 2005, 44:9108-9116.
• [6]Galle J, Lehmann-Bodem C, Hübner U, Heinloth A, Wanner C: CyA and OxLDL cause endothelial dysfunction in isolated arteries through endothelin-mediated stimulation of O(2)(-) formation. Nephrol Dial Transplant 2000, 15:339-346.
• [7]Niedowicz DM, Daleke DL: The role of oxidative stress in diabetic complications. Cell Biochem Biophys 2005, 43:289-330.
• [8]Stocker R, Keaney JF Jr: Role of oxidative modifications in atherosclerosis. Physiol Rev 2004, 84:1381-1478.
• [9]Kingsley K, Huff JL, Rust WL, Carroll K, Martinez AM, Fitchmun M, Plopper GE: ERK1/2 mediates PDGF-BB-BB stimulated vascular smooth muscle cell proliferation and migration on laminin-5. Biochem Biophys Res Commun 2002, 293:1000-1006.
• [10]Chan JY, Lam FC, Leung PC, Che CT, Fung KP: Anti-hyperglycemic and anti-oxidative effects of an herbal formulation of Radix Astragali, Radix Codonopsis and Cortex Lycii in a mouse model of type 2 diabetes mellitus. Phytother Res 2009, 23:658-665.
• [11]Chan JY, Leung PC, Che CT, Fung KP: Protective effects of an herbal formulation of Radix Astragali, Radix Codonopsis and Cortex Lycii on streptozotocin-induced apoptosis in pancreatic β-cells: An implication for its treatment of diabetes mellitus. Phytother Res 2008, 22:190-196.
• [12]State Pharmacopoeia Commission: Pharmacopoeia of the People's Republic of China. Chemical Industry Press, Beijing, China; 2005.
• [13]Chan JY, Tang PM, Hon PM, Au SW, Tsui SK, Waye MM, Kong SK, Mak TC, Fung KP: Pheophorbide a, a major antitumor component purified from Scutellaria barbata, induces apoptosis in human hepatocellular carcinoma cells. Planta Med 2006, 72:28-33.
• [14]Chan JY, Siu KP, Fung KP: Effect of arsenic trioxide on multidrug resistant hepatocellular carcinoma cells. Cancer Lett 2006, 236:250-258.
• [15]Lähteenmäki TA, Korpela R, Tikkanen MJ, Karjala K, Laakso J, Solatunturi E, Vapaatalo H: Proliferative effects of oxidized low-density lipoprotein on vascular smooth muscle cells: role of dietary habits. Life Sci 1998, 63:995-1003.
• [16]Heinecke JW: Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis 1998, 141:1-15.
• [17]Bicknell KA, Surry EL, Brooks G: Targeting the cell cycle machinery for the treatment of cardiovascular disease. J Pharm Pharmacol 2003, 55:571-591.
• [18]Myllärniemi M, Calderon L, Lemström K, Buchdunger E, Häyry P: Inhibition of platelet-derived growth factor receptor tyrosine kinase inhibits vascular smooth muscle cell migration and proliferation. FASEB J 1997, 11:1119-1126.
• [19]Graf K, Xi XP, Yang D, Fleck E, Hsueh WA, Law RE: Mitogen-activated protein kinase activation is involved in platelet-derived growth factor-directed migration by vascular smooth muscle cells. Hypertension 1997, 29:334-339.
• [20]Schafer KA: The cell cycle: a review. Vet Pathol 1998, 35:461-478.
• [21]Dong LH, Wen JK, Miao SB, Jia ZH, Hu HJ, Sun RH, Wu YL, Han M: Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRbeta-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia. Cell Res 2010, 20:1252-1262.
• [22]Kim TJ, Lee JH, Lee JJ, Yu JY, Hwang BY, Ye SK, Li S, Li G, Pyo MY, Yun YP: Corynoxeine isolated from the Hook of Uncaria rhynchophylla inhibits rat aotic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation. Biol Pharm Bull 2008, (31):2073-2078.