Top

Journal of Diabetes & Metabolic Disorders

Published in:

01-12-2020 | Insulins | Research article

Aqueous Cichorium intybus L. seed extract may protect against acute palmitate-induced impairment in cultured human umbilical vein endothelial cells by adjusting the Akt/eNOS pathway, ROS: NO ratio and ET-1 concentration

Authors: Raziyeh Abdolahipour, Azin Nowrouzi, Masoumeh Babaei Khalili, Alipasha Meysamie, Samin Ardalani

Published in: Journal of Diabetes & Metabolic Disorders | Issue 2/2020

Abstract

Background

Endothelial dysfunction, which is a vascular response to oxidative stress and inflammation, involves a cascade of downstream events that lead to decreased synthesis of insulin-mediated vasodilator nitric oxide (NO) and increased production of vasoconstrictor protein endothelin-1 (ET-1). NO, and ET-1 production by endothelial cells is regulated by phosphatidylinositol 3-kinase (PI3K)-Akt-eNOS axis and mitogen-activated protein kinase (MAPK) axis of the insulin signaling pathway, respectively.

Methods

After treating the human umbilical vein endothelial cells (HUVECs) with either palmitate complexed with bovine serum albumin (BSA) (abbreviated as PA) or the aqueous Cichorium intybus L. (chicory) seed extract (chicory seed extract, abbreviated as CSE) alone, and simultaneously together (PA + CSE), for 3, 12, and 24 h, we evaluated the capacity of CSE to reestablish the PA-induced imbalance between PI3K/Akt/eNOS and MAPK signaling pathways. The level of oxidative stress was determined by fluorimeter. Insulin-induced levels of NO and ET-1 were measured by Griess and ELISA methods, respectively. Western blotting was used to determine the extent of Akt and eNOS phosphorylation.

Results

Contrary to PA that caused an increase in the reactive oxygen species (ROS) levels and attenuated NO production, CSE readjusted the NO/ROS ratio within 12 h. CSE improved the metabolic arm of the insulin signaling pathway by up-regulating the insulin-stimulated phospho-eNOS Ser1177/total eNOS and phospho-Akt Thr308/total Akt ratios and decreased ET-1 levels.

Conclusions

CSE ameliorated the PA-induced endothelial dysfunction not only by its anti-ROS property but also by selectively enhancing the protective arm and diminishing the injurious arm of insulin signaling pathways.

Citi V, Martelli A, Gorica E, Brogi S, Testai L, Calderone V. Role of hydrogen sulfide in endothelial dysfunction: pathophysiology and therapeutic approaches. J Adv Res. 2020. https://doi.org/10.1016/j.jare.2020.05.015.

Daiber A, Chlopicki S. Revisiting pharmacology of oxidative stress and endothelial dysfunction in cardiovascular disease: Evidence for redox-based therapies. Free Rad Biol Med. 2020. https://doi.org/10.1016/j.freeradbiomed.2020.02.026.

Sharma A, Tate M, Mathew G, Vince JE, Ritchie RH, de Haan JB. Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: therapeutic implications. Front Physiol. 2018;9:114. https://doi.org/10.3389/fphys.2018.00114.CrossRefPubMedPubMedCentral

Masaki N, Ido Y, Yamada T, Yamashita Y, Toya T, Takase B, et al. Endothelial insulin resistance of freshly isolated arterial endothelial cells from radial sheaths in patients with suspected coronary artery disease. J Am Heart Assoc. 2019;8(6):e010816. https://doi.org/10.1161/jaha.118.010816.CrossRefPubMedPubMedCentral

Sears B, Perry M. The role of fatty acids in insulin resistance. Lipids Health Dis. 2015;14:121. https://doi.org/10.1186/s12944-015-0123-1.CrossRefPubMedPubMedCentral

Muniyappa R, Sowers JR. Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord. 2013;14(1):5–12. https://doi.org/10.1007/s11154-012-9229-1.CrossRefPubMedPubMedCentral

Richey JM. The vascular endothelium, a benign restrictive barrier? NO! Role of nitric oxide in regulating insulin action. Diabetes. 2013;62(12):4006–8. https://doi.org/10.2337/db13-1395.CrossRefPubMedPubMedCentral

Chinen I, Shimabukuro M, Yamakawa K, Higa N, Matsuzaki T, Noguchi K, et al. Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats. Endocrinol. 2007;148(1):160–5. https://doi.org/10.1210/en.2006-1132.CrossRef

Holmstrom KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol. 2014;15(6):411–21. https://doi.org/10.1038/nrm3801.CrossRefPubMed

10.

Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta. 2014;1840(9):2709–29. https://doi.org/10.1016/j.bbagen.2014.05.017.CrossRefPubMed

11.

Wang X, Tao L, Hai CX. Redox-regulating role of insulin: The essence of insulin effect. Molecular and Cellular Endocrinol. 2012;349(2):111–27. https://doi.org/10.1016/j.mce.2011.08.019.CrossRef

12.

Aghili Khorasani MH. Makhzan-al-Adviah. Rewritten by shams Ardakani MR, Rahimi R, Farjadmand F. 1st ed. 1771. Tehran University of Medical Sciences.

13.

Balbaa SI, Zaki AY, Abdel-Wahab SM. el-Denshary ES, Motazz-Bellah M. preliminary phytochemical and pharmacological investigations of the roots of different varieties of Cichorium intybus. Planta Med. 1973;24(2):133–44. https://doi.org/10.1055/s-0028-1099480.CrossRefPubMed

14.

Nowrouzi A, Pourfarjam Y, Amiri A. Cichorium intybus L. (CI) as an insulin sensitizer. Diabetes. 2013;(62, Suppl. 1):A304.

15.

Ghamarian A, Abdollahi M, Su X, Amiri A, Ahadi A, Nowrouzi A. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats. Daru. 2012;20(1):56. https://doi.org/10.1186/2008-2231-20-56.CrossRefPubMedPubMedCentral

16.

Ceriello A, Testa R, Genovese S. Clinical implications of oxidative stress and potential role of natural antioxidants in diabetic vascular complications. Nutr Metab Cardiovasc Dis. 2016;26(4):285–92. https://doi.org/10.1016/j.numecd.2016.01.006.CrossRefPubMed

17.

Guo R, Zhao B, Wang Y, Wu D, Wang Y, Yu Y, et al. Cichoric acid prevents free-fatty-acid-induced lipid metabolism disorders via regulating Bmal1 in HepG2 cells. J Agric Food Chem. 2018;66(37):9667–78. https://doi.org/10.1021/acs.jafc.8b02147.CrossRefPubMed

18.

Hazra B, Sarkar R, Bhattacharyya S, Roy P. Tumour inhibitory activity of chicory root extract against Ehrlich ascites carcinoma in mice. Fitoterapia. 2002;73(7–8):730–3. https://doi.org/10.1016/S0367-326X(02)00232-0.CrossRefPubMed

19.

Karthikesan K, Pari L, Menon VP. Antihyperlipidemic effect of chlorogenic acid and tetrahydrocurcumin in rats subjected to diabetogenic agents. Chem Biol Interact. 2010;188(3):643–50. https://doi.org/10.1016/j.cbi.2010.07.026.CrossRefPubMed

20.

Kumar G, Mukherjee S, Paliwal P, Singh SS, Birla H, Singh SP, et al. Neuroprotective effect of chlorogenic acid in global cerebral ischemia-reperfusion rat model. Naunyn Schmiedeberg's Arch Pharmacol. 2019;392(10):1293–309. https://doi.org/10.1007/s00210-019-01670-x.CrossRef

21.

Lee YH, Kim DH, Kim YS, Kim TJ. Prevention of oxidative stress-induced apoptosis of C2C12 myoblasts by a Cichorium intybus root extract. Biosci Biotechnol Biochem. 2013;77(2):375–7. https://doi.org/10.1271/bbb.120465.CrossRefPubMed

22.

Liu Q, Chen Y, Shen C, Xiao Y, Wang Y, Liu Z, et al. Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-kappaB. FASEB J. 2017;31(4):1494–507. https://doi.org/10.1096/fj.201601071R.CrossRefPubMed

23.

Milala J, Grzelak-Błaszczyk K, Król B, Juśkiewicz J, Zdunczyk Z. Composition and properties of chicory extracts rich in fructans and polyphenols. Pol J Food Nutr Sci. 2009;59(1):35–43.

24.

Papetti A, Daglia M, Grisoli P, Dacarro C, Gregotti C, Gazzani G. Anti- and pro-oxidant activity of Cichorium genus vegetables and effect of thermal treatment in biological systems. Food Chem. 2006;97(1):157–65. https://doi.org/10.1016/j.foodchem.2005.03.036.CrossRef

25.

Singh H. Anti-diabetic activity of Methanolic extract of chicory roots in streptozocin induced diabetic rats. Int J Pharm. 2013;3:211–6.

26.

Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, et al. Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens. 2006;24(6):1065–73. https://doi.org/10.1097/01.hjh.0000226196.67052.c0.CrossRefPubMed

27.

Tsai KL, Kao CL, Hung CH, Cheng YH, Lin HC, Chu PM. Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action and anti-inflammation capacity. Oncotarget. 2017;8(18):29600–12. https://doi.org/10.18632/oncotarget.16768.CrossRefPubMedPubMedCentral

28.

Zhu D, Wang Y, Du Q, Liu Z, Liu X. Cichoric acid reverses insulin resistance and suppresses inflammatory responses in the glucosamine-induced HepG2 cells. J Agric Food Chem. 2015;63(51):10903–13. https://doi.org/10.1021/acs.jafc.5b04533.CrossRefPubMed

29.

Gehrmann W, Wurdemann W, Plotz T, Jorns A, Lenzen S, Elsner M. Antagonism between saturated and unsaturated fatty acids in ROS mediated lipotoxicity in rat insulin-producing cells. Cell Physiol Biochem. 2015;36(3):852–65. https://doi.org/10.1159/000430261.CrossRefPubMed

30.

Lee H, Lim JY, Choi SJ. Oleate prevents palmitate-induced atrophy via modulation of mitochondrial ROS production in skeletal myotubes. Oxidative Med Cell Longev. 2017;2017:2739721–11. https://doi.org/10.1155/2017/2739721.CrossRef

31.

Perdomo L, Beneit N, Otero YF, Escribano O, Diaz-Castroverde S, Gomez-Hernandez A, et al. Protective role of oleic acid against cardiovascular insulin resistance and in the early and late cellular atherosclerotic process. Cardiovasc Diabetol. 2015;14:75. https://doi.org/10.1186/s12933-015-0237-9.CrossRefPubMedPubMedCentral

32.

Ricchi M, Odoardi MR, Carulli L, Anzivino C, Ballestri S, Pinetti A, et al. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol. 2009;24(5):830–40. https://doi.org/10.1111/j.1440-1746.2008.05733.x.CrossRefPubMed

33.

Jeong SO, Son Y, Lee JH, Cheong YK, Park SH, Chung HT, et al. Resveratrol analog piceatannol restores the palmitic acid-induced impairment of insulin signaling and production of endothelial nitric oxide via activation of anti-inflammatory and antioxidative heme oxygenase-1 in human endothelial cells. Mol Med Rep. 2015;12(1):937–44. https://doi.org/10.3892/mmr.2015.3553.CrossRefPubMedPubMedCentral

34.

Fratantonio D, Cimino F, Molonia MS, Ferrari D, Saija A, Virgili F, et al. Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors. Biochim Biophys Acta. 2017;1862(3):351–7. https://doi.org/10.1016/j.bbalip.2016.12.008.CrossRef

35.

Ye M, Qiu H, Cao Y, Zhang M, Mi Y, Yu J, et al. Curcumin improves palmitate-induced insulin resistance in human umbilical vein endothelial cells by maintaining proteostasis in endoplasmic reticulum. Front Pharmacol. 2017;8:148. https://doi.org/10.3389/fphar.2017.00148.CrossRefPubMedPubMedCentral

36.

Tang Z, Xia N, Yuan X, Zhu X, Xu G, Cui S, et al. PRDX1 is involved in palmitate induced insulin resistance via regulating the activity of p38MAPK in HepG2 cells. Biochem Biophys Res Commun. 2015;465(4):670–7. https://doi.org/10.1016/j.bbrc.2015.08.008.CrossRefPubMed

37.

Park G, Sim Y, Lee W, Sung SH, Oh MS. Protection on skin aging mediated by antiapoptosis effects of the water lily (Nymphaea Tetragona Georgi) via reactive oxygen species scavenging in human epidermal keratinocytes. Pharmacology. 2016;97(5–6):282–93. https://doi.org/10.1159/000444022.CrossRefPubMed

38.

Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5(1):62–71. https://doi.org/10.1006/niox.2000.0319.CrossRefPubMed

39.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed

40.

Fratantonio D, Speciale A, Ferrari D, Cristani M, Saija A, Cimino F. Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside through modulation of Nrf2/Bach1 and NF-κB pathways. Toxicol Lett. 2015;239(3, 152):–60. https://doi.org/10.1016/j.toxlet.2015.09.020.

41.

Zhang M, Wang CM, Li J, Meng ZJ, Wei SN, Li J, et al. Berberine protects against palmitate-induced endothelial dysfunction: involvements of upregulation of AMPK and eNOS and downregulation of NOX4. Mediat Inflamm. 2013;2013:260464–8. https://doi.org/10.1155/2013/260464.CrossRef

42.

Kim JE, Song SE, Kim YW, Kim JY, Park SC, Park YK, et al. Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase a and AMP-activated protein kinase. J Endocrinol. 2010;207(1):35–44. https://doi.org/10.1677/JOE-10-0093.CrossRefPubMed

43.

Mahmoud AM, Wilkinson FL, McCarthy EM, Moreno-Martinez D, Langford-Smith A, Romero M, et al. Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress. FASEB J. 2017;31(10):4636–48. https://doi.org/10.1096/fj.201601244RR.CrossRefPubMedPubMedCentral

44.

Du X, Edelstein D, Obici S, Higham N, Zou MH, Brownlee M. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest. 2006;116(4):1071–80. https://doi.org/10.1172/JCI23354.CrossRefPubMedPubMedCentral

45.

Zeng C, Zhong P, Zhao Y, Kanchana K, Zhang Y, Khan ZA, et al. Curcumin protects hearts from FFA-induced injury by activating Nrf2 and inactivating NF-κB both in vitro and in vivo. J Mol Cell Cardiol. 2015;79:1–12. https://doi.org/10.1016/j.yjmcc.2014.10.002.CrossRefPubMed

46.

Zhao W, Wu C, Li S, Chen X. Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKbeta pathways. Cytokine. 2016;88:167–76. https://doi.org/10.1016/j.cyto.2016.09.005.CrossRefPubMed

47.

Storniolo CE, Roselló-Catafau J, Pintó X, Mitjavila MT, Moreno JJ. Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1. Redox Biol. 2014;2:971–7. https://doi.org/10.1016/j.redox.2014.07.001.CrossRefPubMedPubMedCentral

48.

Sadeghi A, Seyyed Ebrahimi SS, Golestani A, Meshkani R. Resveratrol ameliorates palmitate-induced inflammation in skeletal muscle cells by attenuating oxidative stress and JNK/NF-kappaB pathway in a SIRT1-independent mechanism. J Cell Biochem. 2017;118(9):2654–63. https://doi.org/10.1002/jcb.25868.CrossRefPubMed

49.

Joshi-Barve S, Barve SS, Amancherla K, Gobejishvili L, Hill D, Cave M, et al. Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Hepatology. 2007;46(3):823–30. https://doi.org/10.1002/hep.21752.CrossRefPubMed

50.

Wang S-L, Li Y, Wen Y, Chen Y-F, Na L-X, Li S-T et al. Curcumin, a Potential Inhibitor of Up-regulation of TNF-alpha and IL-6 Induced by Palmitate in 3T3-L1 Adipocytes through NF-kappaB and JNK Pathway. Biomed Environ Sci. 2009;22(1):32–9. https://doi.org/10.1016/S0895-3988(09)60019-2.

51.

Shirasuna K, Takano H, Seno K, Ohtsu A, Karasawa T, Takahashi M, et al. Palmitic acid induces interleukin-1beta secretion via NLRP3 inflammasomes and inflammatory responses through ROS production in human placental cells. J Reprod Immunol. 2016;116:104–12. https://doi.org/10.1016/j.jri.2016.06.001.CrossRefPubMed

52.

Zhou BR, Zhang JA, Zhang Q, Permatasari F, Xu Y, Wu D, et al. Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha via a NF-kappaB-dependent mechanism in HaCaT keratinocytes. Mediat Inflamm. 2013;2013:530429–11. https://doi.org/10.1155/2013/530429.CrossRef

53.

Volpe CM, Abreu LF, Gomes PS, Gonzaga RM, Veloso CA, Nogueira-Machado JA. The production of nitric oxide, IL-6, and TNF-alpha in palmitate-stimulated PBMNCs is enhanced through hyperglycemia in diabetes. Oxid Medicine Cellular Longev. 2014;2014:479587–12. https://doi.org/10.1155/2014/479587.CrossRef

54.

Nakamura S, Takamura T, Matsuzawa-Nagata N, Takayama H, Misu H, Noda H, et al. Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biol Chem. 2009;284(22):14809–18. https://doi.org/10.1074/jbc.M901488200.CrossRefPubMedPubMedCentral

55.

Du J, Fan LM, Mai A, Li JM. Crucial roles of Nox2-derived oxidative stress in deteriorating the function of insulin receptors and endothelium in dietary obesity of middle-aged mice. Br J Pharmacol. 2013;170(5):1064–77. https://doi.org/10.1111/bph.12336.CrossRefPubMedPubMedCentral

56.

Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49(11):1939–45. https://doi.org/10.2337/diabetes.49.11.1939.CrossRefPubMed

57.

Maloney E, Sweet IR, Hockenbery DM, Pham M, Rizzo NO, Tateya S, et al. Activation of NF-kappaB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activation. Arterioscler Thromb Vasc Biol. 2009;29(9):1370–5. https://doi.org/10.1161/ATVBAHA.109.188813.CrossRefPubMedPubMedCentral

58.

Liao Y, Gou L, Chen L, Zhong X, Zhang D, Zhu H, et al. NADPH oxidase 4 and endothelial nitric oxide synthase contribute to endothelial dysfunction mediated by histone methylations in metabolic memory. Free Radic Biol Med. 2018;115:383–94. https://doi.org/10.1016/j.freeradbiomed.2017.12.017.CrossRefPubMed

59.

Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascular Pharmacol. 2018;100:1–19. https://doi.org/10.1016/j.vph.2017.05.005.CrossRef

60.

Cha SH, Hwang Y, Kim KN, Jun HS. Palmitate induces nitric oxide production and inflammatory cytokine expression in zebrafish. Fish Shellfish Immun. 2018;79:163–7. https://doi.org/10.1016/j.fsi.2018.05.025.CrossRef

61.

Ke J, Wei R, Yu F, Zhang J, Hong T. Liraglutide restores angiogenesis in palmitate-impaired human endothelial cells through PI3K/Akt-Foxo1-GTPCH1 pathway. Peptides. 2016;86:95–101. https://doi.org/10.1016/j.peptides.2016.10.009.CrossRefPubMed

62.

Zhang J, Shan Y, Li Y, Luo X, Shi H. Palmitate impairs angiogenesis via suppression of cathepsin activity. Mol Med Rep. 2017;15(6):3644–50. https://doi.org/10.3892/mmr.2017.6463.CrossRefPubMedPubMedCentral

63.

Chen P, Liu H, Xiang H, Zhou J, Zeng Z, Chen R, et al. Palmitic acid induced autophagy increases reactive oxygen species via the Ca2+/PKCα/NOX4 pathway and impairs endothelial function in human umbilical vein endothelial cells. Exp Ther Med. 2019;17(4):2425–32. https://doi.org/10.3892/etm.2019.7269.CrossRefPubMedPubMedCentral

64.

Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan A, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food Chem Toxicol. 2014;72:138–46. https://doi.org/10.1016/j.fct.2014.06.029.CrossRefPubMed

65.

Xiao H, Wang J, Yuan L, Xiao C, Wang Y, Liu X. Chicoric acid induces apoptosis in 3T3-L1 preadipocytes through ROS-mediated PI3K/Akt and MAPK signaling pathways. J Agric Food Chem. 2013;61(7):1509–20. https://doi.org/10.1021/jf3050268.CrossRefPubMed

66.

Allen SA, Clark W, McCaffery JM, Cai Z, Lanctot A, Slininger PJ, et al. Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae. Biotechnol Biofuels. 2010;3:2. https://doi.org/10.1186/1754-6834-3-2.CrossRefPubMedPubMedCentral

67.

Park CM, Jin KS, Lee YW, Song YS. Luteolin and chicoric acid synergistically inhibited inflammatory responses via inactivation of PI3K-Akt pathway and impairment of NF-kappaB translocation in LPS stimulated RAW 264.7 cells. Eur J Pharmacol. 2011;660(2–3):454–9. https://doi.org/10.1016/j.ejphar.2011.04.007.CrossRefPubMed

68.

Gresele P, Pignatelli P, Guglielmini G, Carnevale R, Mezzasoma AM, Ghiselli A, et al. Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J Nutr. 2008;138(9):1602–8. https://doi.org/10.1093/jn/138.9.1602.CrossRefPubMed

69.

Klinge CM, Wickramasinghe NS, Ivanova MM, Dougherty SM. Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J. 2008;22(7):2185–97. https://doi.org/10.1096/fj.07-103366.CrossRefPubMed

70.

Kimbrough CW, Lakshmanan J, Matheson PJ, Woeste M, Gentile A, Benns MV, et al. Resveratrol decreases nitric oxide production by hepatocytes during inflammation. Surgery. 2015;158(4):1095–101; discussion 101. https://doi.org/10.1016/j.surg.2015.07.012.CrossRefPubMed

71.

Takahashi S, Uchiyama T, Toda K. Differential effect of resveratrol on nitric oxide production in endothelial f-2 cells. Biol Pharm Bull. 2009;32(11):1840–3.CrossRefPubMed

72.

Loaiza A, Carretta MD, Taubert A, Hermosilla C, Hidalgo MA, Burgos RA. Differential intracellular calcium influx, nitric oxide production, ICAM-1 and IL8 expression in primary bovine endothelial cells exposed to nonesterified fatty acids. BMC Vet Res. 2016;12(1):38. https://doi.org/10.1186/s12917-016-0654-3.CrossRefPubMedPubMedCentral

73.

de Lima TM, de Sa LL, Scavone C, Curi R. Fatty acid control of nitric oxide production by macrophages. FEBS Lett. 2006;580(13):3287–95. https://doi.org/10.1016/j.febslet.2006.04.091.CrossRefPubMed

74.

Barton M. Endothelial dysfunction and atherosclerosis: Endothelin receptor antagonists as novel therapeutics. Curr Hypertens Rep. 2000;2(1):84–91. https://doi.org/10.1007/s11906-000-0064-5.CrossRefPubMed

75.

Finch J, Conklin DJ. Air pollution-induced vascular dysfunction: potential role of endothelin-1 (ET-1) system. Cardiovasc Toxicol. 2016;16(3):260–75. https://doi.org/10.1007/s12012-015-9334-y.CrossRefPubMedPubMedCentral

76.

Kwok CF, Shih KC, Hwu CM, Ho LT. Linoleic acid and oleic acid increase the endothelin-1 binding and action in cultured rat aortic smooth muscle cells. Metabolism. 2000;49(11):1386–9. https://doi.org/10.1053/meta.2000.17719.CrossRefPubMed

77.

Park JY, Kim YM, Song HS, Park KY, Kim YM, Kim MS, et al. Oleic acid induces endothelin-1 expression through activation of protein kinase C and NF-kappa B. Biochem Biophys Res Commun. 2003;303(3):891–5. https://doi.org/10.1016/s0006-291x(03)00436-4.CrossRefPubMed

78.

Fayyaz S, Henkel J, Japtok L, Kramer S, Damm G, Seehofer D, et al. Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P2 receptor subtype. Diabetologia. 2014;57(2):373–82. https://doi.org/10.1007/s00125-013-3123-6.CrossRefPubMed

79.

Ishii M, Maeda A, Tani S, Akagawa M. Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules. Arch Biochem Biophys. 2015;566:26–35. https://doi.org/10.1016/j.abb.2014.12.009.CrossRefPubMed

80.

Li HB, Yang YR, Mo ZJ, Ding Y, Jiang WJ. Silibinin improves palmitate-induced insulin resistance in C2C12 myotubes by attenuating IRS-1/PI3K/Akt pathway inhibition. Braz J Med Biol Res. 2015;48(5):440–6. https://doi.org/10.1590/1414-431X20144238.CrossRefPubMedPubMedCentral

81.

Nieuwoudt S, Mulya A, Fealy CE, Martelli E, Dasarathy S, Naga Prasad SV, et al. In vitro contraction protects against palmitate-induced insulin resistance in C2C12 myotubes. Am J Physiol Cell Physiol. 2017;313(5):C575–C83. https://doi.org/10.1152/ajpcell.00123.2017.CrossRefPubMedPubMedCentral

82.

Peng Y, Sun Q, Park Y. Chicoric acid promotes glucose uptake and Akt phosphorylation via AMP-activated protein kinase α-dependent pathway. J Funct Foods. 2019;59:8–15. https://doi.org/10.1016/j.jff.2019.05.020.CrossRef

83.

Schlernitzauer A, Oiry C, Hamad R, Galas S, Cortade F, Chabi B, et al. Chicoric acid is an antioxidant molecule that stimulates AMP kinase pathway in L6 myotubes and extends lifespan in Caenorhabditis elegans. PLoS One. 2013;8(11):e78788. https://doi.org/10.1371/journal.pone.0078788.CrossRefPubMedPubMedCentral

84.

Li N, Zhao Y, Yue Y, Chen L, Yao Z, Niu W. Liraglutide ameliorates palmitate-induced endothelial dysfunction through activating AMPK and reversing leptin resistance. Biochem Biophys Res Commun. 2016;478(1):46–52. https://doi.org/10.1016/j.bbrc.2016.07.095.CrossRefPubMed

85.

Weidong C. Palmitate directly stimulates eNOS via AMPK and PI3-kinase activation in cultured endothelial cells (ECs). Diabetes. 2008; 68th scientific session.

86.

Carlomosti F, D'Agostino M, Beji S, Torcinaro A, Rizzi R, Zaccagnini G, et al. Oxidative stress-induced miR-200c disrupts the regulatory loop among SIRT1, FOXO1, and eNOS. Antioxid Redox Signal. 2017;27(6):328–44. https://doi.org/10.1089/ars.2016.6643.CrossRefPubMed

87.

Srinivasan VAR, Raghavan VA, Parthasarathy S. Biochemical basis and clinical consequences of glucolipotoxicity: A primer. Heart Fail Clin. 2012;(8, 4):501–11. https://doi.org/10.1016/j.hfc.2012.06.011.

88.

Arunachalam G, Yao H, Sundar IK, Caito S, Rahman I. SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: role of resveratrol. Biochem Biophys Res Commun. 2010;393(1):66–72. https://doi.org/10.1016/j.bbrc.2010.01.080.CrossRefPubMedPubMedCentral

89.

Horie K, Nanashima N, Maeda H. Phytoestrogenic effects of blackcurrant anthocyanins increased endothelial nitric oxide synthase (eNOS) expression in human endothelial cells and ovariectomized rats. Molecules. 2019;24(7). https://doi.org/10.3390/molecules24071259.

90.

Liu C, Wang W, Lin W, Ling W, Wang D. Established atherosclerosis might be a prerequisite for chicory and its constituent protocatechuic acid to promote endothelium-dependent vasodilation in mice. Mol Nutr Food Res. 2016;60(10):2141–50. https://doi.org/10.1002/mnfr.201600002.CrossRefPubMed

91.

Hernández-Perera O, Pérez-Sala D, Navarro-Antolín J, Sánchez-Pascuala R, Hernández G, Díaz C, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101(12):2711–9. https://doi.org/10.1172/JCI1500.CrossRefPubMedPubMedCentral

92.

de Alwis N, Beard S, Mangwiro YT, Binder NK, Kaitu'u-Lino TJ, Brownfoot FC, et al. Pravastatin as the statin of choice for reducing pre-eclampsia-associated endothelial dysfunction. Pregnancy Hypertens. 2020;20:83–91. https://doi.org/10.1016/j.preghy.2020.03.004.CrossRefPubMed

93.

Mao Y, Wang J, Yu F, Li Z, Li H, Guo C, et al. Ghrelin protects against palmitic acid or lipopolysaccharide-induced hepatocyte apoptosis through inhibition of MAPKs/iNOS and restoration of Akt/eNOS pathways. Biomed Pharmacother. 2016;84:305–13. https://doi.org/10.1016/j.biopha.2016.09.043.CrossRefPubMed

94.

Laurindo FRM, Liberman M, Fernandes DC, Leite PF. Chapter 8 - Endothelium-dependent vasodilation: Nitric oxide and other mediators. In: Da Luz PL, Libby P, ACP C, FRM L, editors. Endothelium and Cardiovascular Diseases, Academic Press; 2018. p. 97–113. https://doi.org/10.1016/C2016-0-03197-2.CrossRef

95.

Sena CM, Pereira AM, Seica R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochim Biophys Acta. 2013;1832(12):2216–31. https://doi.org/10.1016/j.bbadis.2013.08.006.CrossRefPubMed

Title: Aqueous Cichorium intybus L. seed extract may protect against acute palmitate-induced impairment in cultured human umbilical vein endothelial cells by adjusting the Akt/eNOS pathway, ROS: NO ratio and ET-1 concentration
Authors: Raziyeh Abdolahipour
Azin Nowrouzi
Masoumeh Babaei Khalili
Alipasha Meysamie
Samin Ardalani
Publication date: 01-12-2020
Publisher: Springer International Publishing
Keywords: Insulins
Insulins
Published in: Journal of Diabetes & Metabolic Disorders / Issue 2/2020
Electronic ISSN: 2251-6581
DOI: https://doi.org/10.1007/s40200-020-00603-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2020

Anti-inflammatory and antidiabetic effects of grape-derived stilbene concentrate in the experimental metabolic syndrome

Risk factors, incidence, and prevalence of diabetes among rural farm and non-farm residents of Saskatchewan, Canada; a population-based longitudinal cohort study

The effects of omega-3 fatty acids supplementation on metabolic status in pregnant women: a systematic review and meta-analysis of randomized controlled trials

Cymene consumption and physical activity effect in Alzheimer’s disease model: an in vivo and in vitro study

The mental health of healthcare workers in the COVID-19 pandemic: A systematic review

Serum cytokine dependent hematopoietic cell linker (CLNK) as a predictor for the duration of illness in type 2 diabetes mellitus

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage