Cytoprotective and antioxidant effects of Echium amoenum anthocyanin-rich extract in human endothelial cells (HUVECs)

Document Type : Original Research Article

Authors

1 Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Objective: Echium amoenum Fisch. & C.A. Mey. is used for the treatment of various diseases in traditional medicine. This plant is a major source of anthocyanins with beneficial cardiovascular properties such as anti-atherosclerotic and antihypertensive effects. In the present study, the protective and antioxidant effects of anthocyanin-rich E. amoenum extract were evaluated on human vascular endothelial cells (HUVECs) under oxidative stress.
Materials and Methods: Cell viability and oxidative status were assessed on H2O2-induced oxidative stress (0.5 mM H2O2 for 2 h) in HUVECs pretreated by anthocyanin-rich extract from the petals of E. amoenum (25-1000 µg/ml). Cytoprotective effect of the extract was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The hydroperoxides concentration and ferric reducing antioxidant power (FRAP) were assessed in intra- and extra-cellular fluid of pretreated cells.
Results: Pretreatment of HUVECs with E. amoenum extract at the concentrations of 100-1000 µg/ml reduced the cell death resulted from the exposure to H2O2 in a concentration-dependent manner. E. amoenum extract decreased hydroperoxides concentration and increased FRAP value in both intra- and extra-cellular fluid at different concentration ranges. Moreover, it did not show cytotoxic effects at the concentration range of 25-1000 µg/ml.
Conclusion: These results suggest antioxidant and protective effect of anthocyanin-rich extract of the petals of E. amoenum against H2O2-induced oxidative stress in HUVECs. However, further investigations are needed for understanding the detailed mechanisms of cytoprotective effects of this traditional herbal medicine.

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Abed A, Vaseghi G, Jafari E, Fattahian E, Babhadiashar N, Abed M. 2014. Echium Amoenum Fisch. Et Mey: A review on its pharmacological and medicinal properties. Asian J Med Pharm Res, 4: 21-23.
Bell DR, Gochenaur K. 2006. Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol, 100: 1164-1170.
Banerjee D, Madhusoodanan U, Sharanabasappa M, Ghosh S, Jacob J. 2003. Measurement of plasma hydroperoxide concentration by FOX-1 assay in conjunction with triphenylphosphine. Clin Chim Acta, 337: 147-152.
Benzie IF, Strain JJ. 1996. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem, 239: 70-76.
Bertuglia S, Malandrino S, Colantuoni A. 1995. Effect of Vaccinium myrtillus anthocyanosides on ischaemia reperfusion injury in hamster cheek pouch microcirculation. Pharmacol Res, 31: 183-187.
Carr A, Frei B. 2000. The role of natural antioxidants in preserving the biological activity of endothelium-derived nitric oxide. Free Radic Biol Med, 28: 1806-1814.
Diaz MN, Frel B, Vita JA, Keaney JF Jr. 1997. Antioxidants and atherosclerotic heart disease. N Engl J Med, 337: 408-416.
Garcia-Alonso M, Minihane AM, Rimbach G, Rivas-Gonzalo JC, de Pascual-Teresa S. 2009. Red wine anthocyanins are rapidly absorbed in humans and affect monocyte chemoattractant protein 1 levels and antioxidant capacity of plasma. J Nutr Biochem, 20: 521-529.
Gulcin I, Berashvili D, Gepdiremen A. 2005. Antiradical and antioxidant activity of total anthocyanins from Perilla pankinensis decne. J Ethnopharmacol, 101: 287-293.
Hasanloo T, Sepehrifar R, Hajimehdipoor H. 2011. Levels of phenolic compounds and their effects on antioxidant capacity of wild Vaccinium arctostaphylos L. (Qare-Qat) collected from different regions of Iran. Turk J Biol, 35: 371-377.
Hassellund SS, Flaa A, Kjeldsen SE, Seljeflot I, Karlsen A, Erlund I, Rostrup M. 2013. Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men: a double-blind randomized placebo-controlled crossover study. J Hum Hypertens, 27: 100-106.
Hertog MGL, Kromhour D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giapaoli S, Jansen A, Menotti A, et al. 1995. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Arch Intern Med, 155: 381-386.
Higashi Y, Noma K, Yoshizumi M, Kihara Y. 2009. Endothelial function and oxidative stress in cardiovascular diseases. Circ J, 73: 411-418.
Khoo HE, Azlan A, Nurulhuda MH, Ismail A, Abas F, Hamid M, Roowi S. 2013. Antioxidative and cardioprotective properties of anthocyanins from defatted dabai extracts. Evid Based Complement Alternat Med, 2013: 434057.
Ma ZC, Hong Q, Wang YG, Tan HL, Xiao CR, Liang QD, Wang DG, and Gao Y. 2011. Ferulic acid protects lymphocytes from radiation-predisposed oxidative stress through extracellular regulated kinase. Int J Radiat Biol, 87: 130-140.
Mink PJ, Srafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, Jacobs DR. 2007. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr, 85: 895-909.
Oak MH, Bedoui JE, Madeira SV, Chalupsky K, Schini-Kerth VB. 2006. Delphinidin and cyanidin inhibit PDGF (AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK. Br J Pharmacol, 149: 283-290.
Ojeda D, Jiménez-Ferrer E, Zamilpa A, Herrera-Arellano A, Tortoriello J, Alvarez L. 2010. Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. J Ethnopharmacol, 127: 7-10.
Peluso I, Morabito G, Urban L, Ioannone F, Serafini M. 2012. Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst. Endocr Metab Immune Disord Drug Targets, 12:351-360.
Praticò D. Antioxidants and endothelium protection. 2005. Atherosclerosis, 181: 215-224.
Sadeghi-Aliabadi H, Minaiyan M, Dabestan A. 2010. Cytotoxic evaluation of doxorubicin in combination with simvastatin against human cancer cells. Res Pharm Sci, 5: 127-133.
Rechner AR, Kroner C. 2005. Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function. Thromb Res, 116: 327-334.
Scarabelli TM, Mariotto S, Abdel-Azeim S, Shoji K, Darra E, Stephanou A, Chen-Scarabelli C, Marechal JD, Knight R, Ciampa A, Saravolatz L, de Prati AC, Yuan Z, Cavalieri E, Menegazzi M, Latchman D, Pizza C, Perahia D, Suzuki H. 2009. Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury. FEBS Lett, 583: 531-541.
Schulz E, Anter E, Keaney JFJr. 2004. Oxidative stress, antioxidants, and endothelial function. Curr Med Chem, 11:1093-1104.
Toufektsian MC, de Lorgeril M, Nagy N, Salen P, Donati MB, Giordano L, Mock HP, Peterek S, Matros A, Petroni K, Pilu R, Rotilio D, Tonelli C, de Leiris J, Boucher F, Martin C. 2008. Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reperfusion injury. J Nutr, 138: 747-752.
Touyz RM, Briones AM. 2011. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res, 3: 5-14.
Tsuda T, Horio F, Osawa T. 1998. Dietary cyanidin 3-O-B-D-glucoside increases ex vivo oxidative resistance of serum in rats. Lipids, 33: 583-588.
Vogiatzi G, Tousoulis D, Stefanadis C. 2009. The role of oxidative stress in atherosclerosis. Hellenic J Cardiol, 50: 402-409.
Wallace TC. 2011. Anthocyanins in cardiovascular disease. Adv Nutr, 2: 1-7.
Wolf SP. 1994. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol, 233: 182-189.
World Health Organization (W.H.O.). Cardiovascular diseases (CVDs) Fact sheet Nº 317. 2009.
Youdim KA, Martin A, Joseph JA. 2000. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radic Biol Med, 29: 51-60.
Ziberna L, Tramer F, Moze S, Vrhovsek U, Mattivi F, Passamonti S. 2012. Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium. Free Radic Biol Med, 52: 1750-1759.