Flavonoidlerin Kardiyovasküler Sistem ve İyon Kanalları Üzerine Etkileri
Özet
Flavonoidler, meyve ve sebzelerde doğal olarak bulunan fenolik bileşikler olup, antioksidan ve antienflamatuar özellikleri sayesinde kardiyovasküler hastalıkların önlenmesinde kritik bir rol oynamaktadır. Bu bileşikler, kalp ve damar sistemindeki iyon kanallarının modülasyonu yoluyla vazodilatasyon sağlayarak kan basıncını düzenlemekte ve koruyucu etkiler göstermektedir. Özellikle kalsiyum ve potasyum kanalları üzerindeki spesifik etkileri, aritmi ve hipertansiyon gibi rahatsızlıklarda flavonoidlerin yeni nesil terapötik ajanlar olarak kullanılma potansiyelini ortaya koymaktadır.
Flavonoids are phenolic compounds naturally found in fruits and vegetables that play a critical role in preventing cardiovascular diseases through their antioxidant and anti-inflammatory properties. These compounds exhibit protective effects by regulating blood pressure through the modulation of ion channels in the cardiovascular system, which facilitates vasodilation. Their specific actions on calcium and potassium channels, in particular, highlight the potential of flavonoids to serve as next-generation therapeutic agents for conditions such as arrhythmia and hypertension.
Referanslar
Fusi F, Trezza A, Tramaglino M, Sgaragli G, Saponara S, Spiga O. The beneficial health effects of flavonoids on the cardiovascular system: Focus on K(+) channels. Pharmacol Res. 2020;152:104625.
do Nascimento RP, Dos Santos BL, Amparo JAO, Soares JRP, da Silva KC, Santana MR, et al. Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma. Pharmaceutics. 2022;14(1).
Ciumarnean L, Milaciu MV, Runcan O, Vesa SC, Rachisan AL, Negrean V, et al. The Effects of Flavonoids in Cardiovascular Diseases. Molecules. 2020;25(18).
Rusznyak ST, Szent-Györgyi A. Vitamin P: Flavonols as Vitamins. Nature. 1936;138(3479):27-.
Williamson G, Kay CD, Crozier A. The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective. Compr Rev Food Sci Food Saf. 2018;17(5):1054-112.
Ingolfsson HI, Thakur P, Herold KF, Hobart EA, Ramsey NB, Periole X, et al. Phytochemicals perturb membranes and promiscuously alter protein function. ACS Chem Biol. 2014;9(8):1788-98.
Clark JL, Zahradka P, Taylor CG. Efficacy of flavonoids in the management of high blood pressure. Nutr Rev. 2015;73(12):799-822.
Almeida Rezende B, Pereira AC, Cortes SF, Lemos VS. Vascular effects of flavonoids. Curr Med Chem. 2016;23(1):87-102.
Formica JV, Regelson W. Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol. 1995;33(12):1061-80.
Clarkson TB. Soy, soy phytoestrogens and cardiovascular disease. J Nutr. 2002;132(3):566S-9S.
Ayșegül Toy MFT, Yusuf Olgar, Esma Nur Okatan, Sinan Değirmenci, Erkan Tuncay, Belma Turan An Investigation on Effects of Pioglitazone in the Heart Function from Rats with Metabolic Syndrome by Using Electrophysiological Techniques. Journal of Ankara University School of Medicine. 2015;68(1):8.
Fusi F, Spiga O, Trezza A, Sgaragli G, Saponara S. The surge of flavonoids as novel, fine regulators of cardiovascular Cav channels. Eur J Pharmacol. 2017;796:158-74.
Clare JJ. Targeting ion channels for drug discovery. Discov Med. 2010;9(46):253-60.
Sobey CG. Potassium channel function in vascular disease. Arterioscler Thromb Vasc Biol. 2001;21(1):28-38.
Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. Pharmacol Rev. 2015;67(4):821-70.
Reinli K, Block G. Phytoestrogen content of foods--a compendium of literature values. Nutr Cancer. 1996;26(2):123-48.
Wijetunge S, Aalkjaer C, Schachter M, Hughes AD. Tyrosine kinase inhibitors block calcium channel currents in vascular smooth muscle cells. Biochem Biophys Res Commun. 1992;189(3):1620-3.
Chiang CE, Chen SA, Chang MS, Lin CI, Luk HN. Genistein directly inhibits L-type calcium currents but potentiates cAMP-dependent chloride currents in cardiomyocytes. Biochem Biophys Res Commun. 1996;223(3):598-603.
Campos-Toimil M, Orallo F. Effects of (-)-epigallocatechin-3-gallate in Ca2+ -permeable non-selective cation channels and voltage-operated Ca2+ channels in vascular smooth muscle cells. Life Sci. 2007;80(23):2147-53.
Fusi F, Sgaragli G, Saponara S. Mechanism of myricetin stimulation of vascular L-type Ca2+ current. J Pharmacol Exp Ther. 2005;313(2):790-7.
Fusi F, Saponara S, Pessina F, Gorelli B, Sgaragli G. Effects of quercetin and rutin on vascular preparations: a comparison between mechanical and electrophysiological phenomena. Eur J Nutr. 2003;42(1):10-7.
Liu Y, Niu L, Cui L, Hou X, Li J, Zhang X, et al. Hesperetin inhibits rat coronary constriction by inhibiting Ca(2+) influx and enhancing voltage-gated K(+) channel currents of the myocytes. Eur J Pharmacol. 2014;735:193-201.
Carullo G, Ahmed A, Trezza A, Spiga O, Brizzi A, Saponara S, et al. A multitarget semi-synthetic derivative of the flavonoid morin with improved in vitro vasorelaxant activity: Role of CaV1.2 and KCa1.1 channels. Biochem Pharmacol. 2021;185:114429.
Eichhorn B, Dobrev D. Vascular large conductance calcium-activated potassium channels: functional role and therapeutic potential. Naunyn Schmiedebergs Arch Pharmacol. 2007;376(3):145-55.
Grijalva-Guiza RE, Jimenez-Garduno AM, Hernandez LR. Potential Benefits of Flavonoids on the Progression of Atherosclerosis by Their Effect on Vascular Smooth Muscle Excitability. Molecules. 2021;26(12).
Park WS, Han J, Earm YE. Physiological role of inward rectifier K(+) channels in vascular smooth muscle cells. Pflugers Arch. 2008;457(1):137-47.
Duarte J, Perez Vizcaino F, Utrilla P, Jimenez J, Tamargo J, Zarzuelo A. Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships. Gen Pharmacol. 1993;24(4):857-62.
Cogolludo A, Frazziano G, Briones AM, Cobeno L, Moreno L, Lodi F, et al. The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2O2. Role in vasodilatation. Cardiovasc Res. 2007;73(2):424-31.
Sun XH, Ding JP, Li H, Pan N, Gan L, Yang XL, et al. Activation of large-conductance calcium-activated potassium channels by puerarin: the underlying mechanism of puerarin-mediated vasodilation. J Pharmacol Exp Ther. 2007;323(1):391-7.
Xu YC, Leung GP, Wong PY, Vanhoutte PM, Man RY. Kaempferol stimulates large conductance Ca2+ -activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway. Br J Pharmacol. 2008;154(6):1247-53.
Saponara S, Testai L, Iozzi D, Martinotti E, Martelli A, Chericoni S, et al. (+/-)-Naringenin as large conductance Ca(2+)-activated K+ (BKCa) channel opener in vascular smooth muscle cells. Br J Pharmacol. 2006;149(8):1013-21.
Ding L, Jia C, Zhang Y, Wang W, Zhu W, Chen Y, et al. Baicalin relaxes vascular smooth muscle and lowers blood pressure in spontaneously hypertensive rats. Biomed Pharmacother. 2019;111:325-30.
Jin JY, Park SH, Bae JH, Cho HC, Lim JG, Park WS, et al. Uncoupling by (--)-epigallocatechin-3-gallate of ATP-sensitive potassium channels from phosphatidylinositol polyphosphates and ATP. Pharmacol Res. 2007;56(3):237-47.
Chiang CE, Luk HN, Chen LL, Wang TM, Ding PY. Genistein inhibits the inward rectifying potassium current in guinea pig ventricular myocytes. J Biomed Sci. 2002;9(4):321-6.
Li GR, Wang HB, Qin GW, Jin MW, Tang Q, Sun HY, et al. Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs. Circulation. 2008;117(19):2449-57.
Scholz EP, Zitron E, Kiesecker C, Thomas D, Kathofer S, Kreuzer J, et al. Orange flavonoid hesperetin modulates cardiac hERG potassium channel via binding to amino acid F656. Nutr Metab Cardiovasc Dis. 2007;17(9):666-75.
Scholz EP, Zitron E, Kiesecker C, Luck S, Thomas D, Kathofer S, et al. Inhibition of cardiac HERG channels by grapefruit flavonoid naringenin: implications for the influence of dietary compounds on cardiac repolarisation. Naunyn Schmiedebergs Arch Pharmacol. 2005;371(6):516-25.
