Mechanisms of Medicinal Plant Activity on Nitric Oxide (NO) Bioavailability as Prospective Treatments for Atherosclerosis

Author(s): Khojasteh Malekmohammad, Robert D.E. Sewell, Mahmoud Rafieian-Kopaei*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 22 , 2020

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Background and objective: Atherosclerosis is one of the leading causes of human morbidity globally and reduced bioavailability of vascular nitric oxide (NO) has a critical role in the progression and development of the atherosclerotic disease. Loss of NO bioavailability, for example via a deficiency of the substrate (L-arginine) or cofactors for endothelial nitric oxide synthase (eNOS), invariably leads to detrimental vascular effects such as impaired endothelial function and increased smooth muscle cell proliferation, deficiency of the substrate (Larginine) or cofactors for eNOS. Various medicinal plants and their bioactive compounds or secondary metabolites with fewer side effects are potentially implicated in preventing cardiovascular disease by increasing NO bioavailability, thereby ameliorating endothelial dysfunction. In this review, we describe the most notable medicinal plants and their bioactive compounds that may be appropriate for enhancing NO bioavailability, and treatment of atherosclerosis.

Methods: The material in this article was obtained from noteworthy scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar.

Results: Medicinal plants and their bioactive compounds influence NO production through diverse mechanisms including the activation of the nuclear factor kappa B (NF-κB) signaling pathway, activating protein kinase C (PKC)-α, stimulating protein tyrosine kinase (PTK), reducing the conversion of nitrite to NO via nitrate-nitrite reduction pathways, induction of eNOS, activating the phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase B (AKT) (PI3K/AKT/eNOS/NO) pathway and decreasing oxidative stress.

Conclusion: Medicinal plants and/or their constituent bioactive compounds may be considered as safe therapeutic options for enhancing NO bioavailability and prospective preventative therapy for atherosclerosis.

Keywords: Nitric oxide, NO, eNOS, atherosclerosis, medicinal plants, bioactive compounds.

Wang XF, Ye ZX, Chen JY, et al. Roles of nitric oxide signaling pathway in atherosclerosis Atheroscler Open Access 2018; 3(1): 120.
Charakida M, Deanfield JE, Halcox JP. The role of nitric oxide in early atherosclerosis. Eur J Clin Pharmacol 2006; 62: 69-78.
Chen JY, Ye ZX, Wang XF, et al. Nitric oxide bioavailability dysfunction involves in atherosclerosis. Biomed Pharmacother 2018; 97: 423-8.
[] [PMID: 29091892]
Matthys KE, Bult H. Nitric oxide function in atherosclerosis. Mediators Inflamm 1997; 6(1): 3-21.
[] [PMID: 18472828]
Vallance P, Chan N. Endothelial function and nitric oxide: clinical relevance. Heart 2001; 85(3): 342-50.
[] [PMID: 11179281]
Stapleton PA, Goodwill AG, James ME, Brock RW, Frisbee JC. Hypercholesterolemia and microvascular dysfunction: interventional strategies. J Inflamm (Lond) 2010; 7: 54.
[] [PMID: 21087503]
Miller MR, Megson IL. Recent developments in nitric oxide donor drugs. Br J Pharmacol 2007; 151(3): 305-21.
[] [PMID: 17401442]
Tatematsu S, Wakino S, Kanda T, et al. Role of nitric oxide-producing and -degrading pathways in coronary endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol 2007; 18(3): 741-9.
[] [PMID: 17267746]
Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327(6122): 524-6.
[] [PMID: 3495737]
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288(5789): 373-6.
[] [PMID: 6253831]
Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987; 84(24): 9265-9.
[] [PMID: 2827174]
Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988; 333(6174): 664-6.
[] [PMID: 3131684]
Marletta MA. Nitric oxide synthase: aspects concerning structure and catalysis. Cell 1994; 78(6): 927-30.
[] [PMID: 7522970]
Jiang H, Torregrossa AC, Parthasarathy DK, Bryan NS. Natural product nitric oxide chemistry: new activity of old medicines. Evid Based Complement Alternat Med 2012; 2012 873210
[] [PMID: 22548122]
Forte M, Conti V, Damato A, et al. Targeting nitric oxide with natural derived compounds as a therapeutic strategy in vascular diseases. Oxid Med Cell Longev 2016; 2016 7364138
[] [PMID: 27651855]
Tsutsui M, Shimokawa H, Otsuji Y, Ueta Y, Sasaguri Y, Yanagihara N. Nitric oxide synthases and cardiovascular diseases: insights from genetically modified mice. Circ J 2009; 73(6): 986-93.
[] [PMID: 19430166]
Tsutsui M, Shimokawa H, Tanimoto A, Yanagihara N, Tamura M, Otsuj Y. Roles of nitric oxide synthases in arteriosclerotic vascular disease: Insights from murine genetic models. J Clin Exp Cardiolog 2014; 5: 2-7.
Xie Q-W, Cho HJ, Calaycay J, et al. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 1992; 256(5054): 225-8.
[] [PMID: 1373522]
Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994; 78(6): 915-8.
[] [PMID: 7522969]
Costa ED, Rezende BA, Cortes SF, Lemos VS. Neuronal nitric oxide synthase in vascular physiology and diseases. Front Physiol 2016; 7: 206-14.
[] [PMID: 27313545]
Rafikov R, Fonseca FV, Kumar S, et al. eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity. J Endocrinol 2011; 210(3): 271-84.
[] [PMID: 21642378]
Atochin DN, Huang PL. Endothelial nitric oxide synthase transgenic models of endothelial dysfunction. Pflugers Arch 2010; 460(6): 965-74.
[] [PMID: 20697735]
Böger RH, Bode-Böger SM, Frölich JC. The L-arginine-nitric oxide pathway: role in atherosclerosis and therapeutic implications. Atherosclerosis 1996; 127(1): 1-11.
[] [PMID: 9006798]
Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 1999; 34(6): 879-86.
[] [PMID: 10598133]
Clancy RM, Leszczynska-Piziak J, Abramson SB. Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J Clin Invest 1992; 90(3): 1116-21.
[] [PMID: 1325992]
Gliozzi M, Scicchitano M, Bosco F, et al. Modulation of nitric oxide synthases by oxidized LDLs: Role in vascular inflammation and atherosclerosis development. Int J Mol Sci 2019; 20(13): 3294-310.
[] [PMID: 31277498]
Sukhovershin RA, Yepuri G, Ghebremariam YT. Endothelium-derived nitric oxide as an antiatherogenic mechanism: implications for therapy. Methodist DeBakey Cardiovasc J 2015; 11(3): 166-71.
[] [PMID: 26634024]
Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991; 88(11): 4651-5.
[] [PMID: 1675786]
Gauthier TW, Davenpeck KL, Lefer AM. Nitric oxide attenuates leukocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion. Am J Physiol 1994; 267(4 Pt 1): G562-8.
[PMID: 7524346]
Tsao PS, McEvoy LM, Drexler H, Butcher EC, Cooke JP. Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine. Circulation 1994; 89(5): 2176-82.
[] [PMID: 8181143]
von der Leyen HE, Gibbons GH, Morishita R, et al. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci USA 1995; 92(4): 1137-41.
[] [PMID: 7532305]
Ellenby MI, Ernst CB, Carretero OA, Scicli AG. Role of nitric oxide in the effect of blood flow on neointima formation. J Vasc Surg 1996; 23(2): 314-22.
[] [PMID: 8637109]
Farhy RD, Carretero OA, Ho KL, Scicli AG. Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation. Circ Res 1993; 72(6): 1202-10.
[] [PMID: 7684331]
Shaw CA, Megson IL, Rossi AG. Apoptosis and atherosclerosis: The role of nitric oxide. Antiinflamm Antiallergy Agents Med Chem 2006; 5: 27-33.
Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ. Nitric oxide and atherosclerosis: an update. Nitric Oxide 2006; 15(4): 265-79.
[] [PMID: 16684613]
Muller G, Morawietz H. Nitric oxide, NAD(P)H oxidase, and atherosclerosis. Antioxid Redox Signal 2009; 11(7): 1711-31.
[] [PMID: 19257809]
Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006; 113(13): 1708-14.
[] [PMID: 16585403]
Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J 2009; 73(3): 411-8.
[] [PMID: 19194043]
Parthasarathy S, Santanam N. Mechanisms of oxidation, antioxidants, and atherosclerosis. Curr Opin Lipidol 1994; 5(5): 371-5.
[] [PMID: 7858912]
Malekmohammad K, Rafieian-Kopaei M, Sardari S, Sewell RD. Toxicological effects of Mentha x piperita (peppermint): a review. Toxin Rev 2019; 1-15.
Katz SD, Biasucci L, Sabba C, et al. Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol 1992; 19(5): 918-25.
[] [PMID: 1552112]
Ludmer PL, Selwyn AP, Shook TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315(17): 1046-51.
[] [PMID: 3093861]
Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 2006; 291(3): H985-H1002.
[] [PMID: 16632549]
Grassi D, Desideri G, Ferri C. Flavonoids: antioxidants against atherosclerosis. Nutrients 2010; 2(8): 889-902.
[] [PMID: 22254061]
Napoli C, Ignarro LJ. Nitric oxide and atherosclerosis. Nitric Oxide 2001; 5(2): 88-97.
[] [PMID: 11292358]
Soydinç S, Çelik A, Demiryürek S, Davutoğlu V, Tarakçıoğlu M, Aksoy M. The relationship between oxidative stress, nitric oxide, and coronary artery disease. Eur J Gen Med 2007; 4: 62-6.
Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997; 272(34): 20963-6.
[] [PMID: 9261091]
Li H, Förstermann U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Curr Opin Pharmacol 2013; 13(2): 161-7.
[] [PMID: 23395155]
Vásquez-Vivar J, Kalyanaraman B, Martásek P, et al. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 1998; 95(16): 9220-5.
[] [PMID: 9689061]
Wang W, Wang S, Yan L, et al. Superoxide production and reactive oxygen species signaling by endothelial nitric-oxide synthase. J Biol Chem 2000; 275(22): 16899-903.
[] [PMID: 10747895]
Goncharov NV, Avdonin PV, Nadeev AD, Zharkikh IL, Jenkins RO, Jenkins R. Reactive oxygen species in pathogenesis of atherosclerosis. Curr Pharm Des 2015; 21(9): 1134-46.
[] [PMID: 25312724]
Malekmohammad K, Sewell RDE, Rafieian-Kopaei M. Antioxidants and Atherosclerosis: Mechanistic Aspects. Biomolecules 2019; 9(8): 301-19.
[] [PMID: 31349600]
Landmesser U, Dikalov S, Price SR, et al. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest 2003; 111(8): 1201-9.
[] [PMID: 12697739]
Bec N, Gorren ACF, Voelker C, Mayer B, Lange R. Reaction of neuronal nitricoxide synthase with oxygen at low temperature. J Biol Chem 1998; 273: 13502-8.
[] [PMID: 9593685]
Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol 2008; 294(4): H1530-40.
[] [PMID: 18192221]
Pong T, Huang PL. Effects of nitric oxide on atherosclerosis. Atherosclerosis 2015; 355-64.
Cheng C, van Haperen R, de Waard M, et al. Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique. Blood 2005; 106(12): 3691-8.
[] [PMID: 16105973]
Hishikawa K, Lüscher TF. Pulsatile stretch stimulates superoxide production in human aortic endothelial cells. Circulation 1997; 96(10): 3610-6.
[] [PMID: 9396462]
Duerrschmidt N, Stielow C, Muller G, Pagano PJ, Morawietz H. NO-mediated regulation of NAD(P)H oxidase by laminar shear stress in human endothelial cells. J Physiol 2006; 576(Pt 2): 557-67.
[] [PMID: 16873416]
Vergnani L, Hatrik S, Ricci F, et al. Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production : key role of L-arginine availability. Circulation 2000; 101(11): 1261-6.
[] [PMID: 10725285]
Ignarro LJ, Napoli C. Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis. Curr Atheroscler Rep 2004; 6(4): 281-7.
[] [PMID: 15191702]
Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989; 2(8670): 997-1000.
[] [PMID: 2572793]
Rochette L, Lorin J, Zeller M, et al. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? Pharmacol Ther 2013; 140(3): 239-57.
[] [PMID: 23859953]
Bartnicki P, Kowalczyk M, Franczyk-Skóra B, Baj Z, Rysz J. Evaluation of endothelial (dys) function, left ventricular structure and function in patients with chronic kidney disease. Curr Vasc Pharmacol 2016; 14(4): 360-7.
[] [PMID: 26759218]
Tran CT, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway. Atheroscler Suppl 2003; 4(4): 33-40.
[] [PMID: 14664901]
Shatanawi A, Lemtalsi T, Yao L, Patel C, Caldwell RB, Caldwell RW. Angiotensin II limits NO production by upregulating arginase through a p38 MAPK-ATF-2 pathway. Eur J Pharmacol 2015; 746: 106-14.
[] [PMID: 25446432]
Lee J, Bae EH, Ma SK, Kim SW. Altered nitric oxide system in cardiovascular and renal diseases. Chonnam Med J 2016; 52(2): 81-90.
[] [PMID: 27231671]
Satoh K, Fukumoto Y, Shimokawa H. Rho-kinase: important new therapeutic target in cardiovascular diseases. Am J Physiol Heart Circ Physiol 2011; 301(2): H287-96.
[] [PMID: 21622831]
Batchelor TJ, Sadaba JR, Ishola A, Pacaud P, Munsch CM, Beech DJ. Rho-kinase inhibitors prevent agonist-induced vasospasm in human internal mammary artery. Br J Pharmacol 2001; 132(1): 302-8.
[] [PMID: 11156590]
Chen Y, Zhao S, Wang Y, et al. Homocysteine reduces protein S-nitrosylation in endothelium. Int J Mol Med 2014; 34(5): 1277-85.
[] [PMID: 25189662]
Bryan NS. Nitric oxide enhancement strategies. Future Sci OA 2015; 1(1): FSO48.
[] [PMID: 28031863]
Herman AG, Moncada S. Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis. Eur Heart J 2005; 26(19): 1945-55.
[] [PMID: 15911567]
Papapetropoulos A, Fulton D, Lin MI, et al. Vanadate is a potent activator of endothelial nitric-oxide synthase: evidence for the role of the serine/threonine kinase Akt and the 90-kDa heat shock protein. Mol Pharmacol 2004; 65(2): 407-15.
[] [PMID: 14742683]
Adebayo SA, Dzoyem JP, Shai LJ, Eloff JN. The anti-inflammatory and antioxidant activity of 25 plant species used traditionally to treat pain in southern African. BMC Complement Altern Med 2015; 15: 159-69.
[] [PMID: 26014115]
Medeiros IA, Santos MRV, Nascimento NMS, Duarte JC. Cardiovascular effects of Sida cordifolia leaves extract in rats. Fitoterapia 2006; 77(1): 19-27.
[] [PMID: 16257496]
Chung HS, Jeong HJ, Kim JS, et al. Activation of inducible nitric oxide synthase by Euonymus alatus in mouse peritoneal macrophages. Clin Chim Acta 2002; 318(1-2): 113-20.
[] [PMID: 11880120]
Chung HS, Jeong HJ, Han MJ, et al. Nitric oxide and tumor necrosis factor-alpha production by Ixeris dentata in mouse peritoneal macrophages. J Ethnopharmacol 2002; 82(2-3): 217-22.
[] [PMID: 12241998]
Chung HS, Jeong HJ, Hong SH, et al. Induction of nitric oxide synthase by Oldenlandia diffusa in mouse peritoneal macrophages. Biol Pharm Bull 2002; 25(9): 1142-6.
[] [PMID: 12230105]
Punturee K, Wild CP, Vinitketkumneun U. Thai medicinal plants modulate nitric oxide and tumor necrosis factor-α in J774.2 mouse macrophages. J Ethnopharmacol 2004; 95(2-3): 183-9.
[] [PMID: 15507334]
Grande S, Bogani P, de Saizieu A, Schueler G, Galli C, Visioli F. Vasomodulating potential of mediterranean wild plant extracts. J Agric Food Chem 2004; 52(16): 5021-6.
[] [PMID: 15291469]
Koo HN, Hong SH, Seo HG, et al. Inulin stimulates NO synthesis via activation of PKC-α and protein tyrosine kinase, resulting in the activation of NF-kappaB by IFN-γ-primed RAW 264.7 cells. J Nutr Biochem 2003; 14(10): 598-605.
[] [PMID: 14559111]
Rininger JA, Kickner S, Chigurupati P, McLean A, Franck Z. Immunopharmacological activity of Echinacea preparations following simulated digestion on murine macrophages and human peripheral blood mononuclear cells. J Leukoc Biol 2000; 68(4): 503-10.
[PMID: 11037971]
Goel V, Chang C, Slama J, et al. Echinacea stimulates macrophage function in the lung and spleen of normal rats. J Nutr Biochem 2002; 13(8): 487-92.
[] [PMID: 12165361]
Kim GY, Choi GS, Lee SH, Park YM. Acidic polysaccharide isolated from Phellinus linteus enhances through the up-regulation of nitric oxide and tumor necrosis factor-α from peritoneal macrophages. J Ethnopharmacol 2004; 95(1): 69-76.
[] [PMID: 15374609]
Kwan CY, Zhang WB, Deyama T, Nishibe S. Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark extract is mediated by NO and EDHF in small vessels. Naunyn Schmiedebergs Arch Pharmacol 2004; 369(2): 206-11.
[] [PMID: 14673511]
Zheng XF, Kwan CY, Daniel EE. β-Adrenoceptor activates endothelium-dependent release of nitric oxide in rat aorta. Zhongguo Yao Li Xue Bao 1995; 16(5): 385-90.
[PMID: 8701749]
Mohebbati R, Iranmanesh M, Beheshti F, et al. The effect of some herbal extracts on nitric oxide production in endothelial cells 3T3 cell line. Iran J Pharm Sci 2016; 12: 1-10.
Parul R, Kundu SK, Saha P. In vitro nitric oxide scavenging activity of methanol extracts of three Bangladeshi medicinal plants. The pharma innovation 2013; 1: 83-90.
Tang Y, Garg H, Geng YJ, Bryan NS. Nitric oxide bioactivity of traditional Chinese medicines used for cardiovascular indications. Free Radic Biol Med 2009; 47(6): 835-40.
[] [PMID: 19545619]
Sun YY, Su XH, Jin JY, et al. Rumex acetosa L. induces vasorelaxation in rat aorta via activation of PI3-kinase/Akt- AND Ca(2+)-eNOS-NO signaling in endothelial cells. J Physiol Pharmacol 2015; 66(6): 907-15.
[PMID: 26769840]
Hwang SM, Lee YJ, Yoon JJ, et al. Prunella vulgaris suppresses HG-induced vascular inflammation via Nrf2/HO-1/eNOS activation. Int J Mol Sci 2012; 13(1): 1258-68.
[] [PMID: 22312316]
Park SH, Shim BS, Yoon JS, et al. Vascular protective effect of an ethanol extract of Camellia japonica fruit: endothelium-dependent relaxation of coronary artery and reduction of smooth muscle cell migration. Oxid Med Cell Longev 2016; 2016 6309565
[PMID: 26697138]
Mendonça-Filho RR, Rodrigues IA, Alviano DS, et al. Leishmanicidal activity of polyphenolic-rich extract from husk fiber of Cocos nucifera Linn. (Palmae). Res Microbiol 2004; 155(3): 136-43.
[] [PMID: 15059625]
Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17(4): 299-305.
[] [PMID: 12722128]
Zhou L, Zuo Z, Chow MS. Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. J Clin Pharmacol 2005; 45(12): 1345-59.
[] [PMID: 16291709]
Zhang SY, Chen G, Wei PF, et al. The effect of puerarin on serum nitric oxide concentration and myocardial eNOS expression in rats with myocardial infarction. J Asian Nat Prod Res 2008; 10(3-4): 373-81.
[] [PMID: 18348063]
Koltermann A, Hartkorn A, Koch E, Fürst R, Vollmar AM, Zahler S. Ginkgo biloba extract EGb 761 increases endothelial nitric oxide production in vitro and in vivo. Cell Mol Life Sci 2007; 64(13): 1715-22.
[] [PMID: 17497242]
Ou HC, Hsieh YL, Yang NC, et al. Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism. J Appl Physiol 2013; 114(2): 274-85.
[] [PMID: 23195633]
Kim JH, Park SH, Kim YW, et al. The traditional herbal medicine, Dangkwisoo-San, prevents cerebral ischemic injury through nitric oxide-dependent mechanisms. Evid Based Complement Alternat Med 2011; 2011 718302
[] [PMID: 21423636]
Jahan N, Rahman K, Ali S. Cardioprotective and antilipidemic potential of cyperus rotundus in chemically induced cardiotoxicity. Int J Agric Biol 2012; 14: 989-92.
Maslin DJ, Brown CA, Das I, Zhang XH. Nitric oxide--a mediator of the effects of garlic? Biochem Soc Trans 1997; 25(3): 408S.
[] [PMID: 9388638]
Sooranna SR, Hirani J, Das I. Garlic can induce both GTP cyclohydrolase and nitric oxide synthase activity in choriocarcinoma cells. Biochem Soc Trans 1995; 23(4): 543S.
[] [PMID: 8654728]
Grassi D, Desideri G, Croce G, Tiberti S, Aggio A, Ferri C. Flavonoids, vascular function and cardiovascular protection. Curr Pharm Des 2009; 15(10): 1072-84.
[] [PMID: 19355949]
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79(5): 727-47.
[] [PMID: 15113710]
Anter E, Thomas SR, Schulz E, Shapira OM, Vita JA, Keaney JF Jr. Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols. J Biol Chem 2004; 279(45): 46637-43.
[] [PMID: 15333638]
Gresele P, Pignatelli P, Guglielmini G, et al. Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J Nutr 2008; 138(9): 1602-8.
[] [PMID: 18716157]
Bhatt SR, Lokhandwala MF, Banday AA. Resveratrol prevents endothelial nitric oxide synthase uncoupling and attenuates development of hypertension in spontaneously hypertensive rats. Eur J Pharmacol 2011; 667(1-3): 258-64.
[] [PMID: 21640096]
Lorenz M, Wessler S, Follmann E, et al. A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem 2004; 279(7): 6190-5.
[] [PMID: 14645258]
Kim JA, Formoso G, Li Y, et al. Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J Biol Chem 2007; 282(18): 13736-45.
[] [PMID: 17363366]
Zhang Y, Huang C, Liu S, et al. Effects of quercetin on intracavernous pressure and expression of nitrogen synthase isoforms in arterial erectile dysfunction rat model. Int J Clin Exp Med 2015; 8(5): 7599-605.
[PMID: 26221305]
Perez-Vizcaino F, Duarte J, Jimenez R, Santos-Buelga C, Osuna A. Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 2009; 61(1): 67-75.
[] [PMID: 19307694]
Vera R, Galisteo M, Villar IC, et al. Soy isoflavones improve endothelial function in spontaneously hypertensive rats in an estrogen-independent manner: role of nitric-oxide synthase, superoxide, and cyclooxygenase metabolites. J Pharmacol Exp Ther 2005; 314(3): 1300-9.
[] [PMID: 15958720]
Chen X. Cardiovascular protection by ginsenosides and their nitric oxide releasing action. Clin Exp Pharmacol Physiol 1996; 23(8): 728-32.
[] [PMID: 8886498]
Kim ND, Kang SY, Kim MJ, Park JH, Schini-Kerth VB. The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels. Eur J Pharmacol 1999; 367(1): 51-7.
[] [PMID: 10082264]
Engwerda CR, Andrew D, Murphy M, Mynott TL. Bromelain activates murine macrophages and natural killer cells in vitro. Cell Immunol 2001; 210(1): 5-10.
[] [PMID: 11485347]
Qin M, Luo Y, Meng XB, et al. Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways. Vascul Pharmacol 2015; 70: 23-34.
[] [PMID: 25849952]
Xing SS, Yang XY, Zheng T, et al. Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway. Vascul Pharmacol 2015; 72: 141-52.
[] [PMID: 26187353]
Liu S, Sun Z, Chu P, et al. EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways. Apoptosis 2017; 22(5): 672-80.
[] [PMID: 28317089]
Yamagata K, Tanaka N, Matsufuji H, Chino M. β-carotene reverses the IL-1β-mediated reduction in paraoxonase-1 expression via induction of the CaMKKII pathway in human endothelial cells. Microvasc Res 2012; 84(3): 297-305.
[] [PMID: 22750393]
Jin SW, Choi CY, Hwang YP, et al. Betulinic acid increases eNOS phosphorylation and NO Synthesis via the calcium-signaling pathway. J Agric Food Chem 2016; 64(4): 785-91.
[] [PMID: 26750873]

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Year: 2020
Published on: 04 July, 2020
Page: [2591 - 2601]
Pages: 11
DOI: 10.2174/1381612826666200318152049
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