Abstract
Aim:
To investigate the diverse pharmacological actions of astragaloside IV from the perspective of metabolic syndrome, and to investigate the effect of the drug on the pathogenesis of metabolic syndrome.
Methods:
Adipogenesis was used as an indicator of the effect of astragaloside IV on preadipocyte differentiation, and was measured by using an oil red O assay. Glucose uptake was determined by measuring the transport of [2-3H]-deoxyglucose into the cells. The concentrations of peroxisome proliferator-activated receptor-γ(PPARγ) and aP2 mRNA were determined by using reverse transcription-polymerase chain reaction. Apoptosis and viability loss of endothelial cells were detected by using flow cytometry and the WST-1 assay, respectively. Intracellular free Ca2+ was labeled with Fluo-3 AM and measured by using a laser scanning confocal microscope.
Results:
Astragaloside IV can significantly potentiate insulin-induced preadipocyte differentiation at concentrations of 3, 10, and 30 μg/mL, improve high glucose-induced insulin resistance in adipocytes at a concentration of 30 μg/mL, and prevent tumor necrosis factor (TNF)-α-induced apoptosis and viability loss at concentrations of 10 and 30 μg/mL, and 30 μg/mL, respectively, in endothelial cells. Furthermore, we found that these effects were partly due to the promotion of PPARγ expression and to the inhibition of abnormal TNF-α-induced intracellular free Ca2+ accumulation in endothelial cells.
Conclusion:
The diverse pharmacological actions of astragaloside IV can all be linked to metabolic syndrome pathogenesis. Our study provides a new insight into the mechanism by which astragaloside IV exerts its effect.
References
- 1.
Wu F, Chen X. A review of pharmacological study on Astragalus membranaceus (Fisch) Bge. Zhong Yao Cai 2004; 27: 232–4.
- 2.
Jiang QL, Jiang JW, Lu XX. Effect of astragaloside IV on glucagon-like peptide-1. Chin J Gerontol 2003; 23: 52–3.
- 3.
Zhang YD, Wang YL, Sheng JP. Effect of astragaloside IV on inflammatory and hypertension. Acta Pharmacol Sin 1984; 19: 333–7.
- 4.
Cao Q, Li ZP. Effects of astragaloside IV on myocardial calcium transport and cardiac function in ischemic rats. Acta Pharmacol Sin 2002; 23: 898–904.
- 5.
Bo I. A major health hazard: the metabolic syndrome. Life Sci 2003; 73: 2395–411.
- 6.
Caballero AE. Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 2003; 11: 1278–89.
- 7.
Rodbell M. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964; 239: 375–80.
- 8.
Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745–56.
- 9.
Ramirez ZJL, Castro MF, Kuri HW. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O. Histochemistry 1992; 97: 493–7.
- 10.
Iijima K, Yoshizumi M, Ako J, Eto M, Kim S, Hashimoto M, et al. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in rat aortic smooth muscle cells. Biochem Biophys Res Commun 1998; 247: 353–6.
- 11.
Olefsky JM. Mechanisms of the ability of insulin to activate the glucose-transport system in rat adipocytes. Biochem J 1978; 172: 137–45.
- 12.
Spyridopoulos I, Brogi E, Kearney M, Sullivan AB, Cetrulo C, Isner JM, et al. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-α: balance between growth and death signals. J Mol Cell Cardiol 1997; 29: 1321–30.
- 13.
Fukunaga Y, Itoh H, Doi K, Tanaka T, Yamashita J, Chun TH, et al. Thiazolidinediones, peroxisome proliferator-activated receptor γagonists, regulate endothelial cell growth and secretion of vasoactive peptides, Atherosclerosis 2001; 158: 113–9.
- 14.
Wang LZ, Zhang QZ, Hu XZ, Lun N, Zhu FH. Verapamil, cyproheptadine, and anisodamine antagonized (Ca2+)i elevation induced by TNF-α in a single endothelial cell. Acta Pharmacol Sin 2001; 22: 918–22.
- 15.
Fujiwara T, Horikoshi H. Troglitazone and related compounds: therapeutic potential beyond diabetes. Life Sci 2000; 67: 2405–16.
- 16.
Peter J. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004; 53 Suppl 1: S143–51.
- 17.
Okuno A, Tamemoto H, Tobe K. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 1998; 101: 1354–61.
- 18.
Wang CC, Goalstone ML, Draznin B. Molecular mechanisms of insulin resistance that impact cardiovascular biology. Diabetes 2004; 53: 2735–40.
- 19.
Wang SH, Wang WJ, Wang XF, Chen W. Effect of Astragalus polysaccharides and berberine on carbohydrate metabolism and cell differentiation in 3T3-L1 adipocytes. Chin J Int Tradit West 2004; 24: 926–8.
- 20.
Yang LH, Qu DJ, Feng ZK, Lu J, Liu Y, Wu WJ. Effect of Radix astragali on insulin sensitivity in high-fat-fed rats. Acad J Sec Milit Med Univ 2004; 25: 407–9.
- 21.
Kota BP, Huang TH, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacol Res 2005; 51: 85–94.
- 22.
Torp-Pedersen C, Rask-Madsen C, Gustafsson I, Gustafsson F, Kober L. Diabetes mellitus and cardiovascular risk: just another risk factor? Eur Heart J 2003; Suppl 5–6: F26–32.
- 23.
Winkler G, Lakatos P, Salamon F, Nagy Z, Speer G, Kovacs M, et al. Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet Med 1999; 16: 207–11.
- 24.
Rajala MW, Scherer PE. Scherer minireview. The adipocyte: at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003; 144: 3765–73.
- 25.
Gobe G, Browning J, Howard T, Hogg N, Winterford C, Cross R. Apoptosis occurs in endothelial cells during hypertensioninduced microvascular rarefaction. J Struct Biol 1997; 118: 63–72.
- 26.
Kaiser S, Hennig B, Toborek M. Apoptosis of vascular endothelial cells in response to TNF and lipid treatments. Atherosclerosis 1997; 134: 243–4.
- 27.
Fan Y, Wu DZ, Hu ZB. Effects of astragaloside IV on the enhance of endothelial permeability induced by histamine. Chin J Bas Med TCM 2001; 7: 36–8.
- 28.
Choy JC, Granville DJ, Hunt DW, McManus BM. Endothelial cell apoptosis: biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol 2001; 33: 1673–90.
- 29.
Toborek M, Blanc EM, Kaiser S, Mattson MP, Hennig B. Linoleic acid potentiates TNF-mediated oxidative stress, disruption of calcium homeostasis, and apoptosis of cultured vascular endothelial cells. J Lipid Res 1997; 38: 2155–67.
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Department of Biomedical Engineering, Hangzhou Dianzi University, Hangzhou 310018, China
- Ming-en Xu
Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China
- Ming-en Xu
- , Shang-zhi Xiao
- , Yong-hong Sun
- , Yang Ou-yang
- & Xiao-xiang Zheng
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