title: Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells.
abstract: Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a major antiatherogenic factor in the blood vessel. Oxidative stress plays an important role in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Decreased availability of endothelial NO promotes the progression of endothelial dysfunction and atherosclerosis. Rutin is a flavonoid with multiple cardiovascular protective effects. This study aimed to investigate the effects of rutin on eNOS and NO production in cultured human umbilical vein endothelial cells (HUVEC). HUVEC were divided into four groups: control; oxidative stress induction with 180 μM H₂O₂; treatment with 300 μM rutin; and concomitant induction with rutin and H₂O₂ for 24 hours. HUVEC treated with rutin produced higher amount of NO compared to control (P < 0.01). In the oxidative stress-induced HUVEC, rutin successfully induced cells' NO production (P < 0.01). Rutin promoted NO production in HUVEC by inducing eNOS gene expression (P < 0.05), eNOS protein synthesis (P < 0.01), and eNOS activity (P < 0.05). Treatment with rutin also led to increased gene and protein expression of basic fibroblast growth factor (bFGF) in HUVEC. Therefore, upregulation of eNOS expression by rutin may be mediated by bFGF. The results showed that rutin may improve endothelial function by augmenting NO production in human endothelial cells.
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Azizah
authors.identifier: 0000-0001-8268-3316
authors.initials: A
authors.lastname: Ugusman
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Zaiton
authors.initials: Z
authors.lastname: Zakaria
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Kien Hui
authors.initials: KH
authors.lastname: Chua
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Nor Anita Megat Mohd
authors.initials: NA
authors.lastname: Nordin
authors.affiliation: Department of Obstetrics and Gynaecology, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.
authors.forename: Zaleha
authors.initials: Z
authors.lastname: Abdullah Mahdy
mesh_terms: D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*
chemical_list: D009569:Nitric Oxide; D012431:Rutin; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III
references.citation: Bioessays. 2003 Nov;25(11):1085-95
references.pmid: 14579249
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5889-92
references.pmid: 8392180
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11996-2001
references.pmid: 8876251
references.citation: J Pharm Biomed Anal. 2007 Mar 12;43(4):1580-6
references.pmid: 17196356
references.citation: Circulation. 2006 Apr 4;113(13):1708-14
references.pmid: 16585403
references.citation: Nitric Oxide. 2002 Nov;7(3):149-64
references.pmid: 12381413
references.citation: J Agric Food Chem. 2004 Jul 14;52(14):4414-8
references.pmid: 15237945
references.citation: Can J Surg. 2013 Feb;56(1):6-14
references.pmid: 23187035
references.citation: BMC Complement Altern Med. 2011 Apr 16;11:31
references.pmid: 21496279
references.citation: Endocrinology. 1999 Mar;140(3):1399-407
references.pmid: 10067868
references.citation: Arthritis Res Ther. 2008;10(1):R19
references.pmid: 18252009
references.citation: Cardiovasc Res. 1999 Aug 15;43(3):532-41
references.pmid: 10690325
references.citation: Nitric Oxide. 2002 Sep;7(2):132-47
references.pmid: 12223183
references.citation: Atherosclerosis. 2007 Nov;195(1):e104-11
references.pmid: 17481637
references.citation: Neurosci Lett. 2000 Sep 1;290(3):197-200
references.pmid: 10963897
references.citation: Br J Nutr. 2010 May;103(10):1398-403
references.pmid: 20021702
references.citation: Life Sci. 2003 Dec 19;74(5):603-12
references.pmid: 14623031
references.citation: Science. 1991 Nov 22;254(5035):1208-10
references.pmid: 1957172
references.citation: J Ethnopharmacol. 2004 Aug;93(2-3):173-6
references.pmid: 15234750
references.citation: Am J Physiol. 1995 Nov;269(5 Pt 2):H1583-9
references.pmid: 7503252
references.citation: J Cereb Blood Flow Metab. 1994 Jan;14(1):70-4
references.pmid: 8263060
references.citation: Am J Hypertens. 2008 Jan;21(1):28-34
references.pmid: 18091741
references.citation: FASEB J. 2006 Jul;20(9):1501-3
references.pmid: 16754746
references.citation: Am J Clin Nutr. 2005 Jan;81(1 Suppl):317S-325S
references.pmid: 15640497
references.citation: Circ Res. 2000 Feb 18;86(3):347-54
references.pmid: 10679488
references.citation: Biochem Soc Trans. 2003 Dec;31(Pt 6):1308-11
references.pmid: 14641050
references.citation: Nature. 1987 Jan 15-21;325(6101):257-9
references.pmid: 2433585
references.citation: Mol Pharmacol. 2003 Feb;63(2):297-310
references.pmid: 12527801
references.citation: Mol Med. 2010 Jan-Feb;16(1-2):45-52
references.pmid: 19898633
references.citation: Nitric Oxide. 2006 Sep;15(2):93-102
references.pmid: 16626982
references.citation: Curr Atheroscler Rep. 2004 Jul;6(4):281-7
references.pmid: 15191702
references.citation: J Agric Food Chem. 2009 Sep 9;57(17):7693-9
references.pmid: 19722703
references.citation: Cell. 1995 Jan 27;80(2):179-85
references.pmid: 7834738
references.citation: Can J Physiol Pharmacol. 2005 Dec;83(12):1101-8
references.pmid: 16462909
references.citation: Cell. 2004 Jan 23;116(2):205-19
references.pmid: 14744432
references.citation: EXCLI J. 2012 Nov 09;11:705-714
references.pmid: 27847456
references.citation: Cardiovasc Res. 2005 Oct 1;68(1):26-36
references.pmid: 16009356
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Jan;284(1):R1-12
references.pmid: 12482742
references.citation: Eur J Pharmacol. 2010 Feb 25;628(1-3):27-35
references.pmid: 19931526
references.citation: J Ethnopharmacol. 2010 Mar 2;128(1):123-30
references.pmid: 20051261
references.citation: Science. 1995 Apr 21;268(5209):447-8
references.pmid: 7716553
references.citation: Neurotoxicology. 2006 Jul;27(4):492-500
references.pmid: 16513172
references.citation: Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):405-12
references.pmid: 14656742
references.citation: Mol Aspects Med. 2005 Feb-Apr;26(1-2):33-65
references.pmid: 15722114
references.citation: J Nutr. 2011 Jun;141(6):1062-9
references.pmid: 21508207
references.citation: Angiogenesis. 2001;4(2):91-102
references.pmid: 11806248
references.citation: Biochem J. 1996 Sep 15;318 ( Pt 3):729-47
references.pmid: 8836113
references.citation: Clinics (Sao Paulo). 2010 Jul;65(7):709-14
references.pmid: 20668629
references.citation: J Leukoc Biol. 2000 Mar;67(3):327-34
references.pmid: 10733092