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image of Betanin, a Natural Product from Red Beets, Improves Endothelial Dysfunction through Activation of Autophagy

Abstract

Objective

Endothelial dysfunction is the altered pathological ability of endothelial cells to modulate the passage of cells and solutes across vessels, which underlies the development of inflammatory diseases. Betanin (betanidin-5-O-β-glucoside), a natural product rich in red beets, is a water-soluble nitrogen-containing pigment, and its potential protective effects on cardiovascular disease have been reported. In this study, we investigated the protective role of betanin in vascular endothelial dysfunction induced by TNFα and explored potential mechanisms.

Methods

We modelled endothelial dysfunction through TNFα stimulation in human umbilical vein endothelial cells (HUVECs) and examined the role of betanin and its possible mechanism of action by MTT assay, Western blotting, and immunofluorescence staining. A systemic inflammation model of mice was built through LPS to investigate the protective roles of betanin.

Results

Betanin pre-treatment increased cell viability, inhibited the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and improved endothelial tight junction by upregulating the expression of occludin and zonula occludens-1 (ZO-1) after TNFα stimulation in HUVECs. In terms of endothelial-mesenchymal transition, betanin up-regulated the expression of endothelial phenotypes VE-cadherin and CD31, whereas it inhibited the expression of mesenchymal phenotype N-cadherin, indicating that betanin reduced endothelial-mesenchymal transition in TNFα-stimulated HUVECs. In addition, betanin increased the expression of LC3 and decreased the expression of p62, two central proteins in autophagy. Betanin also reversed the abnormal autophagic flux after TNFα exposure. However, the specific autophagy inhibitor, 3-methyladenine, blocked the protective effect of betanin. Finally, betanin was found to greatly decrease ICAM-1 and VCAM-1 expression, and upregulate occludin and ZO-1 levels in a systemic inflammation model of mice.

Conclusion

The above results collectively suggested that betanin may improve endothelial dysfunction by promoting autophagy, thus exerting beneficial effects on cardiovascular health.

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2025-05-22
2025-09-11

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References

  1. Godo S. Shimokawa H. Endothelial functions. Arterioscler. Thromb. Vasc. Biol. 2017 37 9 e108 e114 10.1161/ATVBAHA.117.309813 28835487
    [Google Scholar]
  2. Clyne A.M. Endothelial response to glucose: Dysfunction, metabolism, and transport. Biochem. Soc. Trans. 2021 49 1 313 325 10.1042/BST20200611 33522573
    [Google Scholar]
  3. Potente M. Gerhardt H. Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011 146 6 873 887 10.1016/j.cell.2011.08.039 21925313
    [Google Scholar]
  4. Krüger-Genge A. Blocki A. Franke R.P. Jung F. Vascular endothelial cell biology: An update. Int. J. Mol. Sci. 2019 20 18 4411 10.3390/ijms20184411 31500313
    [Google Scholar]
  5. Xu S. Ilyas I. Little P.J. Li H. Kamato D. Zheng X. Luo S. Li Z. Liu P. Han J. Harding I.C. Ebong E.E. Cameron S.J. Stewart A.G. Weng J. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: From mechanism to pharmacotherapies. Pharmacol. Rev. 2021 73 3 924 967 10.1124/pharmrev.120.000096 34088867
    [Google Scholar]
  6. Wang Y. Zhan Y. Wang L. Huang X. Xin H.B. Fu M. Qian Y. E3 ubiquitin ligases in endothelial dysfunction and vascular diseases: Roles and potential therapies. J. Cardiovasc. Pharmacol. 2023 82 2 93 103 10.1097/FJC.0000000000001441 37314134
    [Google Scholar]
  7. Wang L. Cheng C.K. Yi M. Lui K.O. Huang Y. Targeting endothelial dysfunction and inflammation. J. Mol. Cell. Cardiol. 2022 168 58 67 10.1016/j.yjmcc.2022.04.011 35460762
    [Google Scholar]
  8. Abd-Elmoniem K.Z. Edwan J.H. Dietsche K.B. Villalobos-Perez A. Shams N. Matta J. Baumgarten L. Qaddumi W.N. Dixon S.A. Chowdhury A. Stagliano M. Mabundo L. Wentzel A. Hadigan C. Gharib A.M. Chung S.T. Endothelial dysfunction in youth-onset type 2 diabetes: A clinical translational study. Circ. Res. 2024 135 6 639 650 10.1161/CIRCRESAHA.124.324272 39069898
    [Google Scholar]
  9. Kim K.A. Kim D. Kim J.H. Shin Y.J. Kim E.S. Akram M. Kim E.H. Majid A. Baek S.H. Bae O.N. Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic stroke models. Fluids Barriers CNS 2020 17 1 21 10.1186/s12987‑020‑00182‑8 32169114
    [Google Scholar]
  10. Martinet W. Knaapen M.W.M. Kockx M.M. De Meyer G.R.Y. Autophagy in cardiovascular disease. Trends Mol. Med. 2007 13 11 482 491 10.1016/j.molmed.2007.08.004 18029229
    [Google Scholar]
  11. Glick D. Barth S. Macleod K.F. Autophagy: Cellular and molecular mechanisms. J. Pathol. 2010 221 1 3 12 10.1002/path.2697 20225336
    [Google Scholar]
  12. Orogo A.M. Gustafsson Å.B. Therapeutic targeting of autophagy: Potential and concerns in treating cardiovascular disease. Circ. Res. 2015 116 3 489 503 10.1161/CIRCRESAHA.116.303791 25634972
    [Google Scholar]
  13. Hashemzaei M. Entezari Heravi R. Rezaee R. Roohbakhsh A. Karimi G. Regulation of autophagy by some natural products as a potential therapeutic strategy for cardiovascular disorders. Eur. J. Pharmacol. 2017 802 44 51 10.1016/j.ejphar.2017.02.038 28238768
    [Google Scholar]
  14. Marzoog B.A. Endothelial cell autophagy in the context of disease development. Anat. Cell Biol. 2023 56 1 16 24 10.5115/acb.22.098 36267005
    [Google Scholar]
  15. Salemkour Y. Lenoir O. Endothelial autophagy dysregulation in diabetes. Cells 2023 12 6 947 10.3390/cells12060947 36980288
    [Google Scholar]
  16. Kheloufi M. Vion A.C. Hammoutene A. Poisson J. Lasselin J. Devue C. Pic I. Dupont N. Busse J. Stark K. Lafaurie-Janvore J. Barakat A.I. Loyer X. Souyri M. Viollet B. Julia P. Tedgui A. Codogno P. Boulanger C.M. Rautou P.E. Endothelial autophagic flux hampers atherosclerotic lesion development. Autophagy 2018 14 1 173 175 10.1080/15548627.2017.1395114 29157095
    [Google Scholar]
  17. Ruart M. Chavarria L. Campreciós G. Suárez-Herrera N. Montironi C. Guixé-Muntet S. Bosch J. Friedman S.L. Garcia-Pagán J.C. Hernández-Gea V. Impaired endothelial autophagy promotes liver fibrosis by aggravating the oxidative stress response during acute liver injury. J. Hepatol. 2019 70 3 458 469 10.1016/j.jhep.2018.10.015 30367898
    [Google Scholar]
  18. Dong Q. Xing W. Fu F. Liu Z. Wang J. Liang X. Zhou X. Yang Q. Zhang W. Gao F. Wang S. Zhang H. Tetrahydroxystilbene glucoside inhibits excessive autophagy and improves microvascular endothelial dysfunction in prehypertensive spontaneously hypertensive rats. Am. J. Chin. Med. 2016 44 7 1393 1412 10.1142/S0192415X16500786 27776426
    [Google Scholar]
  19. Niu C. Chen Z. Kim K.T. Sun J. Xue M. Chen G. Li S. Shen Y. Zhu Z. Wang X. Liang J. Jiang C. Cong W. Jin L. Li X. Metformin alleviates hyperglycemia-induced endothelial impairment by downregulating autophagy via the Hedgehog pathway. Autophagy 2019 15 5 843 870 10.1080/15548627.2019.1569913 30653446
    [Google Scholar]
  20. Lu G. Wu Z. Shang J. Xie Z. Chen C. Zhang C. The effects of metformin on autophagy. Biomed. Pharmacother. 2021 137 111286 10.1016/j.biopha.2021.111286 33524789
    [Google Scholar]
  21. Silva D.V.T. Baião D.S. Ferreira V.F. Paschoalin V.M.F. Betanin as a multipath oxidative stress and inflammation modulator: A beetroot pigment with protective effects on cardiovascular disease pathogenesis. Crit. Rev. Food Sci. Nutr. 2022 62 2 539 554 10.1080/10408398.2020.1822277 32997545
    [Google Scholar]
  22. EFSA panel on food additives and Nutrient sources added to food (ANS). cientific Opinion on the re-evaluation of beetroot red (E 162) as a food additive. EFSA J. 2015 13 12 10.2903/j.efsa.2015.4318
    [Google Scholar]
  23. Esatbeyoglu T. Wagner A.E. Schini-Kerth V.B. Rimbach G. Betanin-A food colorant with biological activity. Mol. Nutr. Food Res. 2015 59 1 36 47 10.1002/mnfr.201400484 25178819
    [Google Scholar]
  24. Li Q. Shen Y. Guo X. Xu Y. Mao Y. Wu Y. He F. Wang C. Chen Y. Yang Y. Betanin dose-dependently ameliorates allergic airway inflammation by attenuating Th2 response and upregulating cAMP–PKA–CREB pathway in asthmatic mice. J. Agric. Food Chem. 2022 70 12 3708 3718 10.1021/acs.jafc.2c00205 35298142
    [Google Scholar]
  25. Polturak G. Aharoni A. “La Vie en Rose”: Biosynthesis, sources, and applications of betalain pigments. Mol. Plant 2018 11 1 7 22 10.1016/j.molp.2017.10.008 29081360
    [Google Scholar]
  26. Kapadia G.J. Tokuda H. Konoshima T. Nishino H. Chemoprevention of lung and skin cancer by Beta vulgaris (beet) root extract. Cancer Lett. 1996 100 1-2 211 214 10.1016/0304‑3835(95)04087‑0 8620443
    [Google Scholar]
  27. da Silva D.V.T. Pereira A.D.A. Boaventura G.T. Ribeiro R.S.A. Verícimo M.A. Carvalho-Pinto C.E. Baião D.S. Del Aguila E.M. Paschoalin V.M.F. Short-term betanin intake reduces oxidative stress in wistar rats. Nutrients 2019 11 9 1978 10.3390/nu11091978 31443409
    [Google Scholar]
  28. Toth S. Jonecova Z. Maretta M. Curgali K. Kalpakidis T. Pribula M. Kusnier M. Fagova Z. Fedotova J. La Rocca G. Rodrigo L. Caprnda M. Zulli A. Ciccocioppo R. Mechirova E. Kruzliak P. The effect of Betanin parenteral pretreatment on Jejunal and pulmonary tissue histological architecture and inflammatory response after Jejunal ischemia-reperfusion injury. Exp. Mol. Pathol. 2019 110 104292 10.1016/j.yexmp.2019.104292 31377235
    [Google Scholar]
  29. Zou X. Yu K. Chu X. Yang L. Betanin alleviates inflammation and ameliorates apoptosis on human oral squamous cancer cells SCC131 and SCC4 through the NF-κB/PI3K/Akt signaling pathway. J. Biochem. Mol. Toxicol. 2022 36 8 e23094 10.1002/jbt.23094 35645143
    [Google Scholar]
  30. Adjuto-Saccone M. Soubeyran P. Garcia J. Audebert S. Camoin L. Rubis M. Roques J. Binétruy B. Iovanna J.L. Tournaire R. TNF-α induces endothelial–mesenchymal transition promoting stromal development of pancreatic adenocarcinoma. Cell Death Dis. 2021 12 7 649 10.1038/s41419‑021‑03920‑4 34172716
    [Google Scholar]
  31. Mizushima N. Yoshimori T. How to interpret LC3 immunoblotting. Autophagy 2007 3 6 542 545 10.4161/auto.4600 17611390
    [Google Scholar]
  32. Joo H.K. Lee Y.R. Lee E.O. Park M.S. Choi S. Kim C.S. Park J.B. Jeon B.H. The extracellular role of Ref-1 as anti-inflammatory function in lipopolysaccharide-induced septic mice. Free Radic. Biol. Med. 2019 139 16 23 10.1016/j.freeradbiomed.2019.05.013 31100475
    [Google Scholar]
  33. Kanner J. Harel S. Granit R. Betalains- a new class of dietary cationized antioxidants. J. Agric. Food Chem. 2001 49 11 5178 5185 10.1021/jf010456f 11714300
    [Google Scholar]
  34. Esatbeyoglu T. Wagner A.E. Motafakkerazad R. Nakajima Y. Matsugo S. Rimbach G. Free radical scavenging and antioxidant activity of betanin: Electron spin resonance spectroscopy studies and studies in cultured cells. Food Chem. Toxicol. 2014 73 119 126 10.1016/j.fct.2014.08.007 25152328
    [Google Scholar]
  35. Abedimanesh N. Asghari S. Mohammadnejad K. Daneshvar Z. Rahmani S. Shokoohi S. Farzaneh A.H. Hosseini S.H. Jafari Anarkooli I. Noubarani M. Andalib S. Eskandari M.R. Motlagh B. The anti-diabetic effects of betanin in streptozotocin-induced diabetic rats through modulating AMPK/SIRT1/NF-κB signaling pathway. Nutr. Metab. 2021 18 1 92 10.1186/s12986‑021‑00621‑9 34656137
    [Google Scholar]
  36. Mousavi M. Abedimanesh N. Mohammadnejad K. Sharini E. Nikkhah M. Eskandari M.R. Motlagh B. Mohammadnejad J. Khodabandehloo H. Fathi M. Talebi M. Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats. Mol. Biol. Rep. 2022 49 10 9345 9354 10.1007/s11033‑022‑07781‑8 35988103
    [Google Scholar]
  37. Fernando G.S.N. Sergeeva N.N. Vagkidis N. Chechik V. Marshall L.J. Boesch C. Differential effects of betacyanin and betaxanthin pigments on oxidative stress and inflammatory response in Murine macrophages. Mol. Nutr. Food Res. 2023 67 15 2200583 10.1002/mnfr.202200583 37203590
    [Google Scholar]
  38. Qiu R. Chen S. Hua F. Bian S. Chen J. Li G. Wu X. Betanin prevents experimental abdominal aortic aneurysm progression by modulating the TLR4/NF-κB and Nrf2/HO-1 pathways. Biol. Pharm. Bull. 2021 44 9 1254 1262 10.1248/bpb.b21‑00042 34471054
    [Google Scholar]
  39. Cohen Tervaert J.W. Kallenberg G.G.M. Cell adhesion molecules in vasculitis. Curr. Opin. Rheumatol. 1997 9 1 16 25 10.1097/00002281‑199701000‑00004 9110129
    [Google Scholar]
  40. Atehortúa L. Rojas M. Vásquez G. Muñoz-Vahos C.H. Vanegas-García A. Posada-Duque R.A. Castaño D. Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res. Ther. 2019 21 1 34 10.1186/s13075‑018‑1796‑4 30674349
    [Google Scholar]
  41. Baselet B. Sonveaux P. Baatout S. Aerts A. Pathological effects of ionizing radiation: Endothelial activation and dysfunction. Cell. Mol. Life Sci. 2019 76 4 699 728 10.1007/s00018‑018‑2956‑z 30377700
    [Google Scholar]
  42. Cavender D.E. Edelbaum D. Ziff M. Endothelial cell activation induced by tumor necrosis factor and lymphotoxin. Am. J. Pathol. 1989 134 3 551 560 2466402
    [Google Scholar]
  43. Bai B. Yang Y. Wang Q. Li M. Tian C. Liu Y. Aung L.H.H. Li P. Yu T. Chu X. NLRP3 inflammasome in endothelial dysfunction. Cell Death Dis. 2020 11 9 776 10.1038/s41419‑020‑02985‑x 32948742
    [Google Scholar]
  44. Vallet B. Bench-to-bedside review: Endothelial cell dysfunction in severe sepsis: A role in organ dysfunction? Crit. Care 2003 7 2 130 138 10.1186/cc1864 12720559
    [Google Scholar]
  45. Peters K. Unger R.E. Brunner J. Kirkpatrick C.J. Molecular basis of endothelial dysfunction in sepsis. Cardiovasc. Res. 2003 60 1 49 57 10.1016/S0008‑6363(03)00397‑3 14522406
    [Google Scholar]
  46. Mittal M. Siddiqui M.R. Tran K. Reddy S.P. Malik A.B. Reactive oxygen species in inflammation and tissue injury. Antioxid. Redox Signal. 2014 20 7 1126 1167 10.1089/ars.2012.5149 23991888
    [Google Scholar]
  47. Imaizumi T. Itaya H. Fujita K. Kudoh D. Kudoh S. Mori K. Fujimoto K. Matsumiya T. Yoshida H. Satoh K. Expression of tumor necrosis factor-alpha in cultured human endothelial cells stimulated with lipopolysaccharide or interleukin-1alpha. Arterioscler. Thromb. Vasc. Biol. 2000 20 2 410 415 10.1161/01.ATV.20.2.410 10669637
    [Google Scholar]
  48. Zhang H. Park Y. Wu J. Chen X. Lee S. Yang J. Dellsperger K.C. Zhang C. Role of TNF-α in vascular dysfunction. Clin. Sci. 2009 116 3 219 230 10.1042/CS20080196 19118493
    [Google Scholar]
  49. Bradley J.R. TNF-mediated inflammatory disease. J. Pathol. 2008 214 2 149 160 10.1002/path.2287 18161752
    [Google Scholar]
  50. Choi H. Nguyen H.N. Lamb F.S. Inhibition of endocytosis exacerbates TNF-α-induced endothelial dysfunction via enhanced JNK and p38 activation. Am. J. Physiol. Heart Circ. Physiol. 2014 306 8 H1154 H1163 10.1152/ajpheart.00885.2013 24561862
    [Google Scholar]
  51. Zuniga M. Gomes C. Chen Z. Martinez C. Devlin J.C. Loke P. Rodriguez A. Plasmodium falciparum and TNF-α differentially regulate inflammatory and barrier integrity pathways in human brain endothelial cells. MBio 2022 13 5 e01746-22 10.1128/mbio.01746‑22 36036514
    [Google Scholar]
  52. Zhou P. Lu S. Luo Y. Wang S. Yang K. Zhai Y. Sun G. Sun X. Attenuation of TNF-α-induced inflammatory injury in endothelial cells by ginsenoside Rb1 via inhibiting NF-κB, JNK and p38 signaling pathways. Front. Pharmacol. 2017 8 464 10.3389/fphar.2017.00464 28824425
    [Google Scholar]
  53. Zhao Y. Shao C. Zhou H. Yu L. Bao Y. Mao Q. Yang J. Wan H. Salvianolic acid B inhibits atherosclerosis and TNF-α-induced inflammation by regulating NF-κB/NLRP3 signaling pathway. Phytomedicine 2023 119 155002 10.1016/j.phymed.2023.155002 37572566
    [Google Scholar]
  54. Yamagata K. Xie Y. Suzuki S. Tagami M. Epigallocatechin-3-gallate inhibits VCAM-1 expression and apoptosis induction associated with LC3 expressions in TNFα-stimulated human endothelial cells. Phytomedicine 2015 22 4 431 437 10.1016/j.phymed.2015.01.011 25925964
    [Google Scholar]
  55. Guttman J.A. Finlay B.B. Tight junctions as targets of infectious agents. Biochim. Biophys. Acta Biomembr. 2009 1788 4 832 841 10.1016/j.bbamem.2008.10.028 19059200
    [Google Scholar]
  56. Cong X. Kong W. Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease. Cell. Signal. 2020 66 109485 10.1016/j.cellsig.2019.109485 31770579
    [Google Scholar]
  57. Bazzoni G. Dejana E. Endothelial cell-to-cell junctions: Molecular organization and role in vascular homeostasis. Physiol. Rev. 2004 84 3 869 901 10.1152/physrev.00035.2003 15269339
    [Google Scholar]
  58. Wallez Y. Huber P. Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis. Biochim. Biophys. Acta Biomembr. 2008 1778 3 794 809 10.1016/j.bbamem.2007.09.003 17961505
    [Google Scholar]
  59. Zhou H. Gao F. Yang X. Lin T. Li Z. Wang Q. Yao Y. Li L. Ding X. Shi K. Liu Q. Bao H. Long Z. Wu Z. Vassar R. Cheng X. Li R. Shen Y. Endothelial BACE1 impairs cerebral small vessels via tight junctions and eNOS. Circ. Res. 2022 130 9 1321 1341 10.1161/CIRCRESAHA.121.320183 35382554
    [Google Scholar]
  60. Li D. Mrsny R.J. Oncogenic Raf-1 disrupts epithelial tight junctions via downregulation of occludin. J. Cell Biol. 2000 148 4 791 800 10.1083/jcb.148.4.791 10684259
    [Google Scholar]
  61. Nowacki L. Vigneron P. Rotellini L. Cazzola H. Merlier F. Prost E. Ralanairina R. Gadonna J.P. Rossi C. Vayssade M. Betanin-enriched red beetroot ( Beta vulgaris L.) extract induces apoptosis and autophagic cell death in MCF-7 cells. Phytother. Res. 2015 29 12 1964 1973 10.1002/ptr.5491 26463240
    [Google Scholar]
  62. Macias-Ceja D.C. Cosín-Roger J. Ortiz-Masiá D. Salvador P. Hernández C. Esplugues J.V. Calatayud S. Barrachina M.D. Stimulation of autophagy prevents intestinal mucosal inflammation and ameliorates murine colitis. Br. J. Pharmacol. 2017 174 15 2501 2511 10.1111/bph.13860 28500644
    [Google Scholar]
  63. Parzych K.R. Klionsky D.J. An overview of autophagy: Morphology, mechanism, and regulation. Antioxid. Redox Signal. 2014 20 3 460 473 10.1089/ars.2013.5371 23725295
    [Google Scholar]
  64. McLeland C.B. Rodriguez J. Stern S.T. Autophagy monitoring assay: Qualitative analysis of MAP LC3-I to II conversion by immunoblot. Methods Mol. Biol. 2011 697 199 206 10.1007/978‑1‑60327‑198‑1_21 21116969
    [Google Scholar]
  65. Lamark T. Svenning S. Johansen T. Regulation of selective autophagy: The p62/SQSTM1 paradigm. Essays Biochem. 2017 61 6 609 624 10.1042/EBC20170035 29233872
    [Google Scholar]
  66. Jiang P. Mizushima N. LC3- and p62-based biochemical methods for the analysis of autophagy progression in mammalian cells. Methods 2015 75 13 18 10.1016/j.ymeth.2014.11.021 25484342
    [Google Scholar]
  67. Kang R. Zeh H.J. Lotze M.T. Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 2011 18 4 571 580 10.1038/cdd.2010.191 21311563
    [Google Scholar]
  68. He Y.L. Li J. Gong S.H. Cheng X. Zhao M. Cao Y. Zhao T. Zhao Y.Q. Fan M. Wu H.T. Zhu L.L. Wu L.Y. BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia. Cell Death Dis. 2022 13 11 966 10.1038/s41419‑022‑05418‑z 36396625
    [Google Scholar]
  69. Dasgupta D. Delmotte P. Sieck G.C. Inflammation-induced protein unfolding in airway smooth muscle triggers a homeostatic response in mitochondria. Int. J. Mol. Sci. 2020 22 1 363 10.3390/ijms22010363 33396378
    [Google Scholar]
  70. Nam J.H. Lee J.H. Choi H.J. Choi S.Y. Noh K.E. Jung N.C. Song J.Y. Choi J. Seo H.G. Jung S.Y. Lim D.S. TNF-α induces mitophagy in rheumatoid arthritis synovial fibroblasts, and mitophagy inhibition alleviates synovitis in collagen antibody-induced arthritis. Int. J. Mol. Sci. 2022 23 10 5650 10.3390/ijms23105650 35628458
    [Google Scholar]
  71. Liu H. Huang H. Li R. Bi W. Feng L. Hu M. Wen W. Mitophagy protects SH-SY5Y neuroblastoma cells against the TNFα-induced inflammatory injury: Involvement of microRNA-145 and Bnip3. Biomed. Pharmacother. 2019 109 957 968 10.1016/j.biopha.2018.10.123 30551550
    [Google Scholar]
  72. Jin K. Shi Y. Zhang H. Zhangyuan G. Wang F. Li S. Chen C. Zhang J. Wang H. Zhang W. Sun B. A TNFα/Miz1-positive feedback loop inhibits mitophagy in hepatocytes and propagates non-alcoholic steatohepatitis. J. Hepatol. 2023 79 2 403 416 10.1016/j.jhep.2023.03.039 37040844
    [Google Scholar]
  73. Takagaki Y. Lee S.M. Dongqing Z. Kitada M. Kanasaki K. Koya D. Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis. Autophagy 2020 16 10 1905 1914 10.1080/15548627.2020.1713641 31965901
    [Google Scholar]
  74. Tian Y.S. Fu X.Y. Yang Z.Q. Wang B. Gao J.J. Wang M.Q. Xu J. Han H.J. Li Z.J. Yao Q.H. Peng R.H. Metabolic engineering of rice endosperm for betanin biosynthesis. New Phytol. 2020 225 5 1915 1922 10.1111/nph.16323 31737907
    [Google Scholar]
  75. Vieira Teixeira da Silva D. Dos Santos Baião D. de Oliveira Silva F. Alves G. Perrone D. Mere Del Aguila E. M Flosi Paschoalin V. Betanin, a natural food additive: Stability, bioavailability, antioxidant and preservative ability assessments. Molecules 2019 24 3 458 10.3390/molecules24030458 30696032
    [Google Scholar]
  76. Kumorkiewicz-Jamro A. Górska R. Krok-Borkowicz M. Reczyńska-Kolman K. Mielczarek P. Popenda Ł. Spórna-Kucab A. Tekieli A. Pamuła E. Wybraniec S. Betalains isolated from underexploited wild plant Atriplex hortensis var. rubra L. exert antioxidant and cardioprotective activity against H9c2 cells. Food Chem. 2023 414 135641 10.1016/j.foodchem.2023.135641 36809729
    [Google Scholar]
  77. Karunamuni G. Sheehan M.M. Doughman Y.Q. Gu S. Sun J. Li Y. Strainic J.P. Rollins A.M. Jenkins M.W. Watanabe M. Supplementation with the methyl donor betaine prevents congenital defects induced by prenatal alcohol exposure. Alcohol. Clin. Exp. Res. 2017 41 11 1917 1927 10.1111/acer.13495 28888041
    [Google Scholar]
  78. Luo M. Wang T. Huang P. Zhang S. Song X. Sun M. Liu Y. Wei J. Shu J. Zhong T. Chen Q. Zhu P. Qin J. Association of Maternal Betaine-Homocysteine Methyltransferase (BHMT) and BHMT2 Genes Polymorphisms with Congenital Heart Disease in Offspring Association of maternal betaine-homocysteine methyltransferase (BHMT) and BHMT2 genes polymorphisms with congenital heart disease in offspring. Reprod. Sci. 2023 30 1 309 325 10.1007/s43032‑022‑01029‑3 35835902
    [Google Scholar]
  79. Vilskersts R. Kuka J. Liepinsh E. Makrecka-Kuka M. Volska K. Makarova E. Sevostjanovs E. Cirule H. Grinberga S. Dambrova M. Methyl-γ-butyrobetaine decreases levels of acylcarnitines and attenuates the development of atherosclerosis. Vascul. Pharmacol. 2015 72 101 107 10.1016/j.vph.2015.05.005 25989106
    [Google Scholar]
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Betanin, a Natural Product from Red Beets, Improves Endothelial Dysfunction through Activation of Autophagy
Bentham Science Publishers ; https://doi.org/10.2174/0109298673244974250507034834
/content/journals/cmc/10.2174/0109298673244974250507034834
/content/journals/cmc/10.2174/0109298673244974250507034834
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  • Article Type:     Research Article
Keywords: Betanin ; autophagic flux ; adhesion molecule ; endothelial dysfunction ; ZO-1 autophagy

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