萝卜硫素对心血管疾病的影响研究进展
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摘要
氧化应激在心血管疾病(CVD)的病理生理学中起着重要作用。一些研究表明活性氧或氮物质的过量产生,在缺血性心肌损伤和随后的心脏功能障碍的发病机制中起到主要作用。萝卜硫素(SFN)是一种异硫氰酸酯(ITC),广泛分布在十字花科蔬菜中,流行病学研究中被认为在体内具有抗癌活性。最新数据表明,SFN在心血管疾病中的有益作用得益于其抗氧化和抗炎特性。文章总结临床研究和动物实验的证据,探索SFN保护CVD的潜在机制。
Oxidative stress plays an important role in the pathophysiology of cardiovascular disease(CVD). Some studies have shown that excessive production of reactive oxygen species or nitrogen substances plays a major role in the pathogenesis of ischemic myocardial injury and subsequent cardiac dysfunction. Sulphur radish(SFN) is an isothiocyanate(ITC), widely distributed in cruciferous vegetables, which has been considered to have anti-cancer activity in vivo and epidemiological studies. Recent data show that the beneficial effects of SFN in cardiovascular diseases are due to its antioxidant and anti-inflammatory properties. This article summarizes the evidence from clinical studies and animal experiments to explore the potential mechanism of SFN in protecting CVD.
Oxidative stress plays an important role in the pathophysiology of cardiovascular disease(CVD). Some studies have shown that excessive production of reactive oxygen species or nitrogen substances plays a major role in the pathogenesis of ischemic myocardial injury and subsequent cardiac dysfunction. Sulphur radish(SFN) is an isothiocyanate(ITC), widely distributed in cruciferous vegetables, which has been considered to have anti-cancer activity in vivo and epidemiological studies. Recent data show that the beneficial effects of SFN in cardiovascular diseases are due to its antioxidant and anti-inflammatory properties. This article summarizes the evidence from clinical studies and animal experiments to explore the potential mechanism of SFN in protecting CVD.
引文
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[19] Derosa G,Sahebkar A,Maffioli P.The role of various peroxisome proliferator-activated receptors and their ligands in clinical practice[J].J Cell Physiol,2018,233(1):153-161.DOI:10.1002/jcp.25804.
[20] Han L,Shen WJ,Bittner S,et al.PPARs:regulators of metabolism and as therapeutic targets in cardiovascular disease.Part Ⅱ:PPAR-β/δ and PPAR-γ[J].Future Cardiol,2017,13(3):279-296.DOI:10.2217/fca-2017-0019.
[21] Janani C,Ranjitha Kumari BD.PPAR gamma gene-a review[J].Diabetes Metab Syndr,2015,9(1):46-50.DOI:10.1016/j.dsx.2014.09.015.
[22] Higashi Y,Kihara Y,Noma K.Endothelial dysfunction and hypertension in aging[J].Hypertension Research,2012,35(11):1039-1047.DOI:10.1038/hr.2012.138.
[23] Senanayake GVK,Banigesh A,Wu L,et al.The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats[J].American Journal of Hypertension,2012,25(2):229-235.DOI:10.1038/ajh.2011.200.
[24] Vanduchova A,Anzenbacher P,Anzenbacherova E.Isothiocyanate from Broccoli,Sulforaphane,and Its Properties[J].J Med Food,2019,22(2):121-126.DOI:10.1089/jmf.2018.0024.
[25] Sillesen H,Fuster V.Predicting coronary heart disease:from framingham risk score to ultrasound bioimaging[J].The Mount Sinai Journal of Medicine,2012,79(6):654-663.DOI:10.1002/msj.21343.
[26] Murakami S.Taurine and atherosclerosis[J].Amino Acids,2014,46(1):73-80.DOI:10.1007/s00726-012-1432-6.
[27] Gijsen F,van der Giessen A,van der Steen A,et al.Shear stress and advanced atherosclerosis in human coronary arteries[J].Journal of Biomechanics,2013,46(2):240-247.DOI:10.1016/j.jbiomech.2012.11.006.
[28] Nigro P,Abe JI,Berk BC.Flow shear stress and atherosclerosis:a matter of site specificity[J].Antioxidants and Redox Signaling,2011,15(5):1405-1414.DOI:10.1089/ ars.2010.3679.
[29] Kim JY,Park HJ,Um SH,et al.Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-α-stimulated mouse vascular smooth muscle cells:involvement of the MAPK,NF-κB and AP-1 signaling pathways[J].Vascular Pharmacology,2012,56(3-4):131-141.DOI:10.1016/j.vph.2011.11.007.
[30] Huang CS,Lin AH,Liu CT,et al.Isothiocyanates protect against oxidized LDL-induced endothelial dysfunction by upregulating Nrf2-dependent antioxidation and suppressing NFκB activation[J].Molecular Nutrition and Food Research,2013,57(11):1918-1930.DOI:10.1002/mnfr.201300063.
[31] Choi KM,Lee YS,Kim W,et al.Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice[J].The Journal of Nutritional Biochemistry,2014,25(2):201-207.DOI:10.1016/j.jnutbio.2013.10.007.
[32] Chuang WY,Kung PH,Kuo CY,et al.Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway[J].Thrombosis and Haemostasis,2013,109(6):1120-1130.DOI:10.1160/th12-09-0636.
[33] Oh CH,Shin JI,Mo SJ,et al.Antiplatelet activity of L-sulforaphane by regulation of platelet activation factors,glycoprotein Ⅱb/Ⅲa and thromboxane A2[J].Blood Coagulation and Fibrinolysis,2013,24(5):498-504.DOI:10.1097/MBC.0b013e32835e4275.
[34] Jayakumar T,Chen WF,Lu WJ,et al.A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase:ex vivo and in vivo studies[J].The Journal of Nutritional Biochemistry,2013,24(6):1086-1095.DOI:10.1016/j.jnutbio.2012.08.007.
[35] Li Z,Galli U,Becker LE,et al.Sulforaphane protects hearts from early injury after experimental transplantation[J].Annals of Transplantation,2013,18(1):558-566.DOI:10.12659/ aot.889342.
[36] Bai Y,Cui W,Xin Y,et al.Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation[J].Journal of Molecular and Cellular Cardiology,2013,57(1):82-95.DOI:10.1016/j.yjmcc.2013.01.008.
[37] Zhang Z,Wang S,Zhou S,et al.Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway[J].Journal of Molecular and Cellular Cardiology,2014,77:42-52.DOI:10.1016/ j.yjmcc.2014.09.022.
[2] Kovacic JC,Fuster V.From treating complex coronary artery disease to promoting cardiovascular health:therapeutic transitions and challenges,2010-2020[J].Clinical Pharmacology & Therapeutics,2011,90(4):509-518.DOI:10.1038/clpt.2011.173.
[3] Halter JB,Musi N,McFarland Horne F,et al.Diabetes and cardiovascular disease in older adults:current status and future directions[J].Diabetes,2014,63(8):2578-2589.DOI:10.2337/db14-0020.
[4] Ichihara S.The pathological roles of environmental and redox stresses in cardiovascular diseases[J].Environmental Health and Preventive Medicine,2013,18(3):177-184.DOI:10.1007/s12199-012-0326-2.
[5] Mukherjee S,Gangopadhyay H,Das DK.Broccoli:a unique vegetable that protects mammalian hearts through the redox cycling of the thioredoxin superfamily[J].Journal of Agricultural and Food Chemistry,2008,56(2):609-617.DOI:10.1021/jf0728146.
[6] Guerrero-Beltrána CE,Calderón-Oliver M,Pedraza-Chaverri J,et al.Protective effect of sulforaphane against oxidative stress:Recent advances[J].Exp Toxicol Pathol,2012,64(5):503-508.DOI:10.1016/j.etp.2010.11.005.
[7] Fernandes RO,De Castro AL,Bonetto JH,et al.Sulforaphane effects on postinfarction cardiac remodeling in rats:Modulation of redox-sensitive prosurvival and proapoptotic proteins[J].J Nutr Biochem,2016,34:106-117.DOI:10.1016/j.jnutbio.2016.05.004.
[8] Townsend BE,Johnson RW.Sulforaphane induces Nrf2 target genes and attenuates inflammatory gene expression in microglia from brain of young adult and aged mice[J].Exp Gerontol,2016,73:42-48.DOI:10.1016/j.exger.2015.11.004.
[9] Cekauskas A,Bruns H,Manikas M,et al.Sulforaphane decreases kidney injury after transplantation in rats:Role of mitochondrial damage[J].Ann Transplant,2013,18:488-496.DOI:10.12659/AOT.884013.
[10] Fuentes F,Paredes-Gonzalez X,Kong AT.Dietary glucosinolates sulforaphane,phenethyl isothiocyanate,indole-3-carbinol/3,3′-diindolylmethane:Anti-oxidative stress/inflammation,Nrf2,epigenetics/epigenomics and in vivo cancer chemopreventive efficacy[J].Curr Pharmacol Rep,2015,1(3):179-196.DOI:10.1007/s40495-015-0017-y.
[11] Suzuki T,Yamamoto M.Molecular basis of the Keap1-Nrf2 system[J].Free Radic Biol Med,2015,88(PtB):93-100.DOI:10.1016/j.freeradbiomed.2015.06.006.
[12] Tebay LE,Robertson H,Durant ST,et al.Mechanisms of activation of the transcription factor Nrf2 by redox stressors,nutrient cues,and energy status and the pathways through which it attenuates degenerative disease[J].Free Radic Biol Med,2015,88(Pt B):108-146.DOI:10.1016/j.freeradbiomed.2015.06.021.
[13] Dinkova-Kostova AT,Fahey JW,Kostov RV,et al.KEAP1 and done Targeting the NRF2 pathway with sulforaphane[J].Trends Food Sci Technol,2017,69(Pt B):257-269.DOI:10.1016/j.tifs.2017.02.002.
[14] Luqman S,Pezzuto JM.NFkappaB:a promising target for natural products in cancer chemoprevention[J].Phytother Res,2010,24(7):949-963.DOI:10.1002/ptr.3171.
[15] Osorio FG,Soria-Valles C,Santiago-Fernández O,et al.NF-κB signaling as a driver of ageing[J].Int Rev Cell Mol Biol,2016,326:133-174.DOI:10.1016/bs.ircmb.2016.04.003.
[16] Lorenzo O,Picatoste B,Ares-Carrasco S,et al.Potential Role of Nuclear Factor κB in Diabetic Cardiomyopathy[J].Mediators Inflamm,2011,2011:652097.DOI:10.1155/2011/652097.
[17] Pamukcu B,Lip GY,Shantsila E.The nuclear factor-kappa B pathway in atherosclerosis:a potential therapeutic target for atherothrombotic vascular disease[J].Thromb Res,2011,128(2):117-123.DOI:10.1016/j.thromres.2011.03.025.
[18] DeCaterina R ,Madonna R.Relevance of new drug discovery to reduce NF-κB activation in cardiovascular disease[J].Vascular Pharmacology,2012,57(1):41-47.DOI:10.1016/j.vph.2012.02.005.
[19] Derosa G,Sahebkar A,Maffioli P.The role of various peroxisome proliferator-activated receptors and their ligands in clinical practice[J].J Cell Physiol,2018,233(1):153-161.DOI:10.1002/jcp.25804.
[20] Han L,Shen WJ,Bittner S,et al.PPARs:regulators of metabolism and as therapeutic targets in cardiovascular disease.Part Ⅱ:PPAR-β/δ and PPAR-γ[J].Future Cardiol,2017,13(3):279-296.DOI:10.2217/fca-2017-0019.
[21] Janani C,Ranjitha Kumari BD.PPAR gamma gene-a review[J].Diabetes Metab Syndr,2015,9(1):46-50.DOI:10.1016/j.dsx.2014.09.015.
[22] Higashi Y,Kihara Y,Noma K.Endothelial dysfunction and hypertension in aging[J].Hypertension Research,2012,35(11):1039-1047.DOI:10.1038/hr.2012.138.
[23] Senanayake GVK,Banigesh A,Wu L,et al.The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats[J].American Journal of Hypertension,2012,25(2):229-235.DOI:10.1038/ajh.2011.200.
[24] Vanduchova A,Anzenbacher P,Anzenbacherova E.Isothiocyanate from Broccoli,Sulforaphane,and Its Properties[J].J Med Food,2019,22(2):121-126.DOI:10.1089/jmf.2018.0024.
[25] Sillesen H,Fuster V.Predicting coronary heart disease:from framingham risk score to ultrasound bioimaging[J].The Mount Sinai Journal of Medicine,2012,79(6):654-663.DOI:10.1002/msj.21343.
[26] Murakami S.Taurine and atherosclerosis[J].Amino Acids,2014,46(1):73-80.DOI:10.1007/s00726-012-1432-6.
[27] Gijsen F,van der Giessen A,van der Steen A,et al.Shear stress and advanced atherosclerosis in human coronary arteries[J].Journal of Biomechanics,2013,46(2):240-247.DOI:10.1016/j.jbiomech.2012.11.006.
[28] Nigro P,Abe JI,Berk BC.Flow shear stress and atherosclerosis:a matter of site specificity[J].Antioxidants and Redox Signaling,2011,15(5):1405-1414.DOI:10.1089/ ars.2010.3679.
[29] Kim JY,Park HJ,Um SH,et al.Sulforaphane suppresses vascular adhesion molecule-1 expression in TNF-α-stimulated mouse vascular smooth muscle cells:involvement of the MAPK,NF-κB and AP-1 signaling pathways[J].Vascular Pharmacology,2012,56(3-4):131-141.DOI:10.1016/j.vph.2011.11.007.
[30] Huang CS,Lin AH,Liu CT,et al.Isothiocyanates protect against oxidized LDL-induced endothelial dysfunction by upregulating Nrf2-dependent antioxidation and suppressing NFκB activation[J].Molecular Nutrition and Food Research,2013,57(11):1918-1930.DOI:10.1002/mnfr.201300063.
[31] Choi KM,Lee YS,Kim W,et al.Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice[J].The Journal of Nutritional Biochemistry,2014,25(2):201-207.DOI:10.1016/j.jnutbio.2013.10.007.
[32] Chuang WY,Kung PH,Kuo CY,et al.Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway[J].Thrombosis and Haemostasis,2013,109(6):1120-1130.DOI:10.1160/th12-09-0636.
[33] Oh CH,Shin JI,Mo SJ,et al.Antiplatelet activity of L-sulforaphane by regulation of platelet activation factors,glycoprotein Ⅱb/Ⅲa and thromboxane A2[J].Blood Coagulation and Fibrinolysis,2013,24(5):498-504.DOI:10.1097/MBC.0b013e32835e4275.
[34] Jayakumar T,Chen WF,Lu WJ,et al.A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase:ex vivo and in vivo studies[J].The Journal of Nutritional Biochemistry,2013,24(6):1086-1095.DOI:10.1016/j.jnutbio.2012.08.007.
[35] Li Z,Galli U,Becker LE,et al.Sulforaphane protects hearts from early injury after experimental transplantation[J].Annals of Transplantation,2013,18(1):558-566.DOI:10.12659/ aot.889342.
[36] Bai Y,Cui W,Xin Y,et al.Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation[J].Journal of Molecular and Cellular Cardiology,2013,57(1):82-95.DOI:10.1016/j.yjmcc.2013.01.008.
[37] Zhang Z,Wang S,Zhou S,et al.Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway[J].Journal of Molecular and Cellular Cardiology,2014,77:42-52.DOI:10.1016/ j.yjmcc.2014.09.022.