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image of Targeting Neuropeptide Y: Novel Approaches to the Treatment of Cardiovascular and Haematological Disorders

Abstract

Background

The 36-amino acid peptide known as neuropeptide Y (NPY) is widely expressed in both the central and peripheral nerve systems and is essential for regulating energy balance, stress responses, cardiovascular function, and immunological regulation through G-protein-coupled Y receptors (Y1, Y2, Y4, Y5).

Objective

To explore the various functions of NPY in hematological and cardiovascular disorders and investigate potential therapeutic approaches that target NPY signaling networks.

Methods

A comprehensive literature analysis focused on NPY-mediated mechanisms in cardiovascular diseases (CVDs) and hematological disorders. The review highlights pharmacological modulators, including synthetic analogs, receptor-specific agents, enzyme inhibitors, and natural substances.

Results

NPY dysregulation promotes vasoconstriction and inflammation, particularly through Y1 receptor activation, contributing to diseases such as atherosclerosis, heart failure, and hypertension. In hematological disorders, NPY influences hematopoiesis, immune cell activity, and angiogenesis, affecting conditions such as thrombosis and leukemia. Therapeutic approaches include receptor-specific agonists and antagonists (e.g., [Leu31, Pro34]NPY, BAY 53-6206), enzyme inhibitors (DPP4, NEP), and natural substances (flavonoids, polyphenols, saponins). Although therapeutic resistance remains a challenge, glucocorticoids also affect NPY expression.

Conclusion

NPY acts as a crucial modulator in hematological and cardiovascular disorders. Understanding its receptor-specific functions enables the development of targeted therapeutic strategies. Natural substances provide promising adjuncts for modulating NPY activity, supporting integrated approaches for treating NPY-related disorders.

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2026-01-20
2026-02-28
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References

  1. Tan C.M.J. Green P. Tapoulal N. Lewandowski A.J. Leeson P. Herring N. The role of neuropeptide Y in cardiovascular health and disease. Front. Physiol. 2018 9 1281 10.3389/fphys.2018.01281 30283345
    [Google Scholar]
  2. Zheng Y. Zhang L. Xie J. Shi L. The emerging role of neuropeptides in Parkinson’s disease. Front. Aging Neurosci. 2021 13 646726 10.3389/fnagi.2021.646726 33762925
    [Google Scholar]
  3. Petrescu A.D. An S.Y. Venter J. McMillin M. DeMorrow S. The role of hypothalamic neuropeptides in regulation of liver functions in health and disease. Endocrines 2023 4 2 457 487 10.3390/endocrines4020034
    [Google Scholar]
  4. Nelson T.S. Allen H.N. Khanna R. Neuropeptide Y and Pain: Insights from Brain Research. ACS Pharmacol. Transl. Sci. 2024 7 12 3718 3728 10.1021/acsptsci.4c00333 39698268
    [Google Scholar]
  5. Timper K. Brüning J.C. Hypothalamic circuits regulating appetite and energy homeostasis: Pathways to obesity. Dis. Model. Mech. 2017 10 6 679 689 10.1242/dmm.026609 28592656
    [Google Scholar]
  6. Enman N.M. Sabban E.L. McGonigle P. Van Bockstaele E.J. Targeting the neuropeptide Y system in stress-related psychiatric disorders. Neurobiol. Stress 2015 1 33 43 10.1016/j.ynstr.2014.09.007 25506604
    [Google Scholar]
  7. Wen X. Zhang B. Wu B. Xiao H. Li Z. Li R. Xu X. Li T. Signaling pathways in obesity: Mechanisms and therapeutic interventions. Signal Transduct. Target. Ther. 2022 7 1 298 10.1038/s41392‑022‑01149‑x 36031641
    [Google Scholar]
  8. Reichmann F. Holzer P. Neuropeptide Y. Neuropeptide Y. A stressful review. Neuropeptides 2016 55 99 109 10.1016/j.npep.2015.09.008 26441327
    [Google Scholar]
  9. Schüß C. Behr V. Beck-Sickinger A.G. Illuminating the neuropeptide Y4 receptor and its ligand pancreatic polypeptide from a structural, functional, and therapeutic perspective. Neuropeptides 2024 105 102416 10.1016/j.npep.2024.102416 38430725
    [Google Scholar]
  10. Gupta A. Osadchiy V. Mayer E.A. Brain–gut–microbiome interactions in obesity and food addiction. Nat. Rev. Gastroenterol. Hepatol. 2020 17 11 655 672 10.1038/s41575‑020‑0341‑5 32855515
    [Google Scholar]
  11. Farzi A. Reichmann F. Holzer P. The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour. Acta Physiol. 2015 213 3 603 627 10.1111/apha.12445 25545642
    [Google Scholar]
  12. Assan D. Mustapha U.F. Chen H. Li Z. Peng Y. Li G. The roles of neuropeptide y (npy) and peptide yy (pyy) in teleost food intake: A mini review. Life 2021 11 6 547 10.3390/life11060547 34200824
    [Google Scholar]
  13. Li C. Wu X. Liu S. Zhao Y. Zhu J. Liu K. Roles of Neuropeptide Y in neurodegenerative and neuroimmune diseases. Front. Neurosci. 2019 13 869 10.3389/fnins.2019.00869 31481869
    [Google Scholar]
  14. Zhang Y. Liu C.Y. Chen W.C. Shi Y.C. Wang C.M. Lin S. He H.F. Regulation of neuropeptide Y in body microenvironments and its potential application in therapies: A review. Cell Biosci. 2021 11 1 151 10.1186/s13578‑021‑00657‑7 34344469
    [Google Scholar]
  15. Tiller C. Reindl M. Holzknecht M. Lechner I. Troger F. Oberhollenzer F. von der Emde S. Kremser T. Mayr A. Bauer A. Metzler B. Reinstadler S.J. Relation of plasma neuropeptide-Y with myocardial function and infarct severity in acute ST-elevation myocardial infarction. Eur. J. Intern. Med. 2024 126 63 68 10.1016/j.ejim.2024.03.027 38555253
    [Google Scholar]
  16. Lambert E.A. Straznicky N.E. Dixon J.B. Lambert G.W. Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity? Am. J. Physiol. Heart Circ. Physiol. 2015 309 2 H244 H258 10.1152/ajpheart.00096.2015 25980020
    [Google Scholar]
  17. Borovac J.A. D’Amario D. Bozic J. Glavas D. Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers. World J. Cardiol. 2020 12 8 373 408 10.4330/wjc.v12.i8.373 32879702
    [Google Scholar]
  18. Park M.H. Jin H.K. Min W.K. Lee W.W. Lee J.E. Akiyama H. Herzog H. Enikolopov G.N. Schuchman E.H. Bae J. Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow. EMBO J. 2015 34 12 1648 1660 10.15252/embj.201490174 25916827
    [Google Scholar]
  19. Kalla M. Hao G. Tapoulal N. Tomek J. Liu K. Woodward L. Dall’Armellina E. Banning A.P. Choudhury R.P. Neubauer S. Kharbanda R.K. Channon K.M. Ajijola O.A. Shivkumar K. Paterson D.J. Herring N. The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade. Eur. Heart J. 2020 41 23 2168 2179 10.1093/eurheartj/ehz852 31834357
    [Google Scholar]
  20. Li M.M. Zheng Y.L. Wang W.D. Lin S. Lin H.L. Neuropeptide Y. An Update on the Mechanism Underlying Chronic Intermittent Hypoxia-Induced Endothelial Dysfunction. Front. Physiol. 2021 12
    [Google Scholar]
  21. Ed Rainger G. Chimen M. Harrison M.J. Yates C.M. Harrison P. Watson S.P. Lordkipanidzé M. Nash G.B. The role of platelets in the recruitment of leukocytes during vascular disease. Platelets 2015 26 6 507 520 10.3109/09537104.2015.1064881 26196409
    [Google Scholar]
  22. Kluess, HA Is neuropeptide Y really involved with regulating resting blood pressure? Am. J. Physiol. Heart Circ. Physiol. 2025 328 1 H157 H158 10.1152/ajpheart.00791.2024
    [Google Scholar]
  23. Saraf R. Mahmood F. Amir R. Matyal R. Neuropeptide Y is an angiogenic factor in cardiovascular regeneration. Eur. J. Pharmacol. 2016 776 64 70 10.1016/j.ejphar.2016.02.033 26875634
    [Google Scholar]
  24. Yi M. Li H. Wu Z. Yan J. Liu Q. Ou C. Chen M. A promising therapeutic target for metabolic diseases: Neuropeptide Y receptors in humans. Cell. Physiol. Biochem. 2018 45 1 88 107 10.1159/000486225 29310113
    [Google Scholar]
  25. Sun W.W. Zhu P. Shi Y.C. Zhang C.L. Huang X.F. Liang S.Y. Song Z.Y. Lin S. Current views on neuropeptide Y and diabetes-related atherosclerosis. Diab. Vasc. Dis. Res. 2017 14 4 277 284
    [Google Scholar]
  26. Hoang J.D. Salavatian S. Yamaguchi N. Swid M.A. Vaseghi M. Vaseghi M. Cardiac sympathetic activation circumvents high-dose beta blocker therapy in part through release of neuropeptide Y. JCI Insight 2020 5 11 e135519 10.1172/jci.insight.135519 32493842
    [Google Scholar]
  27. Shen S Deng Y Shen C Chen H Cheng L Wu C Structural basis of neuropeptide Y signaling through Y1 and Y2 receptors. MedComm 2024 5 7 565 10.1002/mco2.565
    [Google Scholar]
  28. Hofmann S. Bellmann-Sickert K. Beck-Sickinger A.G. Chemical modification of neuropeptide Y for human Y 1 receptor targeting in health and disease. Biol. Chem. 2019 400 3 299 311 10.1515/hsz‑2018‑0364 30653463
    [Google Scholar]
  29. Li Y. Li B. Chen W.D. Wang Y.D. Role of G-protein coupled receptors in cardiovascular diseases. Front. Cardiovasc. Med. 2023 10 1130312 10.3389/fcvm.2023.1130312 37342437
    [Google Scholar]
  30. Zoccali C. Ortiz A. Blumbyte I.A. Rudolf S. Beck-Sickinger A.G. Malyszko J. Spasovski G. Carriazo S. Viggiano D. Kurganaite J. Sarkeviciene V. Rastenyte D. Figurek A. Rroji M. Mayer C. Arici M. Martino G. Tedeschi G. Bruchfeld A. Spoto B. Rychlik I. Wiecek A. Okusa M. Remuzzi G. Mallamaci F. Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges. Nephrol Dial Transplant 2021 37 ii14-ii23.(Suppl. 2) 10.1093/ndt/gfab284 34724060
    [Google Scholar]
  31. Zhu X. Gillespie D.G. Jackson E.K. NPY 1–36 and PYY 1–36 activate cardiac fibroblasts: An effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4. Am. J. Physiol. Heart Circ. Physiol. 2015 309 9 H1528 H1542 10.1152/ajpheart.00070.2015 26371160
    [Google Scholar]
  32. Eugster P.J. Bourdillon N. Vocat C. Wuerzner G. Nguyen T. Millet G.P. Grouzmann E. Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises. Neuropeptides 2022 92 102232 10.1016/j.npep.2022.102232 35180646
    [Google Scholar]
  33. Zheng Y.L. Wang W.D. Li M.M. Lin S. Lin H.L. Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis. Front. Cardiovasc. Med. 2021 8
    [Google Scholar]
  34. Al Musaimi O. Lombardi L. Williams D.R. Albericio F. strategies for improving peptide stability and delivery. pharmaceuticals 2022 15 10 1283 10.3390/ph15101283 36297395
    [Google Scholar]
  35. Li Q. Kang C. Mechanisms of action for small molecules revealed by structural biology in drug discovery. Int. J. Mol. Sci. 2020 21 15 5262 10.3390/ijms21155262 32722222
    [Google Scholar]
  36. Gallo G. Volpe M. Savoia C. Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front. Med. 2022 8 798958 10.3389/fmed.2021.798958 35127755
    [Google Scholar]
  37. Yang C.H. Ann-Onda D. Lin X. Fynch S. Nadarajah S. Pappas E.G. Liu X. Scott J.W. Oakhill J.S. Galic S. Shi Y. Moreno-Asso A. Smith C. Loudovaris T. Levinger I. Eizirik D.L. Laybutt D.R. Herzog H. Thomas H.E. Loh K. Neuropeptide Y1 receptor antagonism protects β-cells and improves glycemic control in type 2 diabetes. Mol. Metab. 2022 55 101413 10.1016/j.molmet.2021.101413 34890851
    [Google Scholar]
  38. Wu Q. Chen J. Hua T. Cai J. Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous System. Neuroendocrinology 2023 113 9 885 904 10.1159/000530804 37094550
    [Google Scholar]
  39. Cai M. Hruby V.J. The melanocortin receptor system: A target for multiple degenerative diseases. Curr. Protein Pept. Sci. 2016 17 5 488 496 10.2174/1389203717666160226145330 26916163
    [Google Scholar]
  40. El Fessikh M. Skhoun H. Ouzzif Z. El Baghdadi J. Deciphering deleterious missense variants in the MC4R gene in the pathogenesis of obesity. Endocrinol. Diabetes Nutr. 2025 72 4 501559 10.1016/j.endien.2025.501559 40221191
    [Google Scholar]
  41. Østergaard S. Kofoed J. Paulsson J.F. Madsen K.G. Jorgensen R. Wulff B.S. Design of Y 2 receptor selective and proteolytically stable PYY 3–36 Analogues. J. Med. Chem. 2018 61 23 10519 10530 10.1021/acs.jmedchem.8b01046 30399314
    [Google Scholar]
  42. Sridhar A. Khan D. Flatt P.R. Irwin N. Moffett R.C. PYY (3-36) protects against high fat feeding induced changes of pancreatic islet and intestinal hormone content and morphometry. Biochim. Biophys. Acta, Gen. Subj. 2023 1867 6 130359 10.1016/j.bbagen.2023.130359 37001706
    [Google Scholar]
  43. Przykaza Ł. Kozniewska E. Ligands of the Neuropeptide Y Y2 Receptors as a Potential Multitarget Therapeutic Approach for the Protection of the Neurovascular Unit Against Acute Ischemia/Reperfusion: View from the Perspective of the Laboratory Bench. Transl. Stroke Res. 2022 13 1 12 24 10.1007/s12975‑021‑00930‑4 34292517
    [Google Scholar]
  44. Fonseca I.C.F. Castelo-Branco M. Cavadas C. Abrunhosa A.J. PET imaging of the neuropeptide Y system: A systematic review. Molecules 2022 27 12 3726 10.3390/molecules27123726 35744852
    [Google Scholar]
  45. Ueda D. Yonemochi N. Kamata T. Shibasaki M. Kamei J. Waddington J.L. Ikeda H. Increase in neuropeptide Y activity impairs social behaviour in association with glutamatergic dysregulation in diabetic mice. Br. J. Pharmacol. 2021 178 3 726 740 10.1111/bph.15326 33197050
    [Google Scholar]
  46. Martins J. Elvas F. Brudzewsky D. Martins T. Kolomiets B. Tralhão P. Gøtzsche C.R. Cavadas C. Castelo-Branco M. Woldbye D.P.D. Picaud S. Santiago A.R. Ambrósio A.F. Activation of Neuropeptide Y receptors modulates retinal ganglion cell physiology and exerts neuroprotective actions in vitro. ASN Neuro 2015 7 4 1759091415598292 10.1177/1759091415598292 26311075
    [Google Scholar]
  47. Tang T. Tan Q. Han S. Diemar A. Löbner K. Wang H. Schüß C. Behr V. Mörl K. Wang M. Chu X. Yi C. Keller M. Kofoed J. Reedtz-Runge S. Kaiser A. Beck-Sickinger A.G. Zhao Q. Wu B. Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors. Sci. Adv. 2022 8 18 eabm1232 10.1126/sciadv.abm1232 35507650
    [Google Scholar]
  48. Tasan R.O. Verma D. Wood J. Lach G. Hörmer B. de Lima T.C.M. Herzog H. Sperk G. The role of Neuropeptide Y in fear conditioning and extinction. Neuropeptides 2016 55 111 126 10.1016/j.npep.2015.09.007 26444585
    [Google Scholar]
  49. Kalafatovic D. Giralt E. Cell-penetrating peptides: Design strategies beyond primary structure and amphipathicity. Molecules 2017 22 11 1929 10.3390/molecules22111929 29117144
    [Google Scholar]
  50. Stadlbauer U. Weber E. Langhans W. Meyer U. The Y2 receptor agonist PYY3–36 increases the behavioural response to novelty and acute dopaminergic drug challenge in mice. Int. J. Neuropsychopharmacol. 2014 17 3 407 419 10.1017/S1461145713001223 24131590
    [Google Scholar]
  51. Henry M. Ghibaudi L. Gao J. Hwa J.J. Energy metabolic profile of mice after chronic activation of central NPY Y1, Y2, or Y5 receptors. Obes. Res. 2005 13 1 36 47 10.1038/oby.2005.6 15761161
    [Google Scholar]
  52. Xu B. Vasile S. Østergaard S. Paulsson J.F. Pruner J. Åqvist J. Wulff B.S. Gutiérrez-de-Terán H. Larhammar D. Elucidation of the Binding Mode of the Carboxyterminal Region of Peptide YY to the Human Y2 Receptor. Mol. Pharmacol. 2018 93 4 323 334 10.1124/mol.117.110627 29367257
    [Google Scholar]
  53. Egan B. Panis R. Hinderliter A. Schork N. Julius S. Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension. J. Clin. Invest. 1987 80 3 812 817 10.1172/JCI113138 3040806
    [Google Scholar]
  54. Baltazi M. Katsiki N. Savopoulos C. Iliadis F. Koliakos G. Hatzitolios A.I. Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study. Am. J. Cardiovasc. Dis. 2011 1 1 48 59 [PMID: 22254185
    [Google Scholar]
  55. Haj-Yehia E. Mertens R.W. Kahles F. Rückbeil M.V. Rau M. Moellmann J. Biener M. Almalla M. Schroeder J. Giannitsis E. Katus H.A. Marx N. Lehrke M. Peptide Y.Y. PYY) is associated with cardiovascular risk in patients with acute myocardial infarction. J. Clin. Med. 2020 9 12 3952 10.3390/jcm9123952 33291235
    [Google Scholar]
  56. Oliveira M.M. Akerman S. Tavares I. Goadsby P.J. Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor: implications for migraine. Pain 2016 157 8 1666 1673 10.1097/j.pain.0000000000000571 27023421
    [Google Scholar]
  57. Domin H. Neuropeptide Y Y2 and Y5 receptors as potential targets for neuroprotective and antidepressant therapies: Evidence from preclinical studies. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021 111 110349 10.1016/j.pnpbp.2021.110349 33991587
    [Google Scholar]
  58. del Carmen Gonzalez-Montelongo M. Meades J.L. Fortuny-Gomez A. Fountain S.J. Neuropeptide Y. Neuropeptide Y. Direct vasoconstrictor and facilitatory effects on P2X1 receptor-dependent vasoconstriction in human small abdominal arteries. Vascul. Pharmacol. 2023 151 107192 10.1016/j.vph.2023.107192 37419269
    [Google Scholar]
  59. Huang Y. Lin X. Lin S. Neuropeptide Y and metabolism syndrome: An update on perspectives of clinical therapeutic intervention strategies. Front. Cell Dev. Biol. 2021 9 695623 10.3389/fcell.2021.695623 34307371
    [Google Scholar]
  60. Krawiec A. Jasikowska K. Chojnacka K. Mitera A. Jochem J. Involvement of central histaminergic system in cardiovascular effects of Y1 receptor antagonist BIBP 3226 in haemorrhagic shock in rats. Annales Academiae Medicae Silesiensis 2017 71 357 362 10.18794/aams/67571
    [Google Scholar]
  61. Keller M. Schindler L. Bernhardt G. Buschauer A. Toward labeled argininamide‐type NPY Y1 receptor antagonists: Identification of a favorable propionylation site in BIBO3304. Arch. Pharm. 2015 348 6 390 398 10.1002/ardp.201400427 25884646
    [Google Scholar]
  62. Pereira F Conceição S. The Role of Y1 receptor in osteoclastogenesis and bone resorption. 2015
    [Google Scholar]
  63. Lee Y. Im E. Immunomodulatory role of neuropeptide Y in intestinal inflammation. Yakhak Hoeji 2023 67 1 1 7 10.17480/psk.2023.67.1.1
    [Google Scholar]
  64. Drexel M. Sperk G. Seizure-induced overexpression of NPY induces epileptic tolerance in a mouse model of spontaneous recurrent seizures. Front. Mol. Neurosci. 2022 15 974784 10.3389/fnmol.2022.974784 36311021
    [Google Scholar]
  65. Chandrasekharan B. Boyer D. Owens J.A. Wolfarth A.A. Saeedi B.J. Dhere T. Iskandar H. Neish A.S. Intracolonic neuropeptide Y Y1 receptor inhibition attenuates intestinal inflammation in murine colitis and cytokine release in IBD biopsies. Inflamm. Bowel Dis. 2022 28 4 502 513 10.1093/ibd/izab243 34613372
    [Google Scholar]
  66. Burkert K. Zellmann T. Meier R. Kaiser A. Stichel J. Meiler J. Mittapalli G.K. Roberts E. Beck-Sickinger A.G. A deep hydrophobic binding cavity is the main interaction for different Y 2 R antagonists. ChemMedChem 2017 12 1 75 85 10.1002/cmdc.201600433 27874262
    [Google Scholar]
  67. Dietrich P. Wormser L. Fritz V. Seitz T. De Maria M. Schambony A. Kremer A.E. Günther C. Itzel T. Thasler W.E. Teufel A. Trebicka J. Hartmann A. Neurath M.F. von Hörsten S. Bosserhoff A.K. Hellerbrand C. Molecular crosstalk between Y5 receptor and neuropeptide Y drives liver cancer. J. Clin. Invest. 2020 130 5 2509 2526 10.1172/JCI131919 31999643
    [Google Scholar]
  68. Lin J. Scullion L. Garland C.J. Dora K. Gβγ subunit signalling underlies neuropeptide Y‐stimulated vasoconstriction in rat mesenteric and coronary arteries. Br. J. Pharmacol. 2023 180 23 3045 3058 10.1111/bph.16192 37460913
    [Google Scholar]
  69. Gibbs T. Tapoulal N. Shanmuganathan M. Burrage M.K. Borlotti A. Banning A.P. Choudhury R.P. Neubauer S. Kharbanda R.K. Ferreira V.M. Channon K.M. Herring N. Channon K.M. Ferreira V.M. De Maria G.L. Dawkins S. Lucking A. Langrish J.P. Banning A.P. Kharbanda R.K. Choudhury R.P. Neuropeptide‐Y Levels in ST‐segment–elevation myocardial infarction: Relationship with coronary microvascular function, heart failure, and mortality. J. Am. Heart Assoc. 2022 11 13 e024850 10.1161/JAHA.121.024850 35766271
    [Google Scholar]
  70. Herring N. Tapoulal N. Kalla M. Ye X. Borysova L. Lee R. Dall’Armellina E. Stanley C. Ascione R. Lu C.J. Banning A.P. Choudhury R.P. Neubauer S. Dora K. Kharbanda R.K. Channon K.M. Banning A.P. Choudhury R.P. Neubauer S. Dora K. Kharbanda R.K. Channon K.M. Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction. Eur. Heart J. 2019 40 24 1920 1929 10.1093/eurheartj/ehz115 30859228
    [Google Scholar]
  71. Cattaneo S. Bettegazzi B. Crippa L. Asth L. Regoni M. Soukupova M. Zucchini S. Cantore A. Codazzi F. Valtorta F. Simonato M. Gene therapy for epilepsy targeting neuropeptide Y and its Y2 receptor to dentate gyrus granule cells. EMBO Rep. 2024 25 10 4387 4409 10.1038/s44319‑024‑00244‑0 39251828
    [Google Scholar]
  72. Chung W.H. Lin Y.N. Wu M.Y. Chang K.C. Sympathetic modulation in cardiac arrhythmias: Where we stand and where we go. J. Pers. Med. 2023 13 5 786 10.3390/jpm13050786 37240956
    [Google Scholar]
  73. Ailanen L. Vähätalo L.H. Salomäki-Myftari H. Mäkelä S. Orpana W. Ruohonen S.T. Savontaus E. Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With Excess Neuropeptide Y, but Enhances Obesity in Control Mice. Front. Pharmacol. 2018 9 319 10.3389/fphar.2018.00319 29674968
    [Google Scholar]
  74. Shoblock J.R. Welty N. Nepomuceno D. Lord B. Aluisio L. Fraser I. In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y2 receptor. Psychopharmacology 2010 208 2 265 277 10.1007/s00213‑009‑1726‑x 19953226
    [Google Scholar]
  75. Tang T. Hartig C. Chen Q. Zhao W. Kaiser A. Zhang X. Zhang H. Qu H. Yi C. Ma L. Han S. Zhao Q. Beck-Sickinger A.G. Wu B. Structural basis for ligand recognition of the neuropeptide Y Y2 receptor. Nat. Commun. 2021 12 1 737 10.1038/s41467‑021‑21030‑9 33531491
    [Google Scholar]
  76. Wagner L. Kaestner F. Wolf R. Stiller H. Heiser U. Manhart S. Hoffmann T. Rahfeld J.U. Demuth H.U. Rothermundt M. von Hörsten S. Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation. Neuropeptides 2016 57 21 34 10.1016/j.npep.2016.02.007 26988064
    [Google Scholar]
  77. Jackson E.K. Gillespie D.G. Tofovic S.P. DPP4 Inhibition, NPY1-36, PYY1-36, SDF-1α, and a hypertensive genetic background conspire to augment cell proliferation and collagen production: Effects that are abolished by low concentrations of 2-Methoxyestradiol. J. Pharmacol. Exp. Ther. 2020 373 1 135 148 10.1124/jpet.119.263467 32015161
    [Google Scholar]
  78. Nakagawa H. Saito Y. Roles of natriuretic peptides and the significance of neprilysin in cardiovascular diseases. biology 2022 11 7 1017 10.3390/biology11071017 36101398
    [Google Scholar]
  79. Bozkurt B. Nair A.P. Misra A. Scott C.Z. Mahar J.H. Fedson S. Neprilysin Inhibitors in Heart Failure. JACC Basic Transl. Sci. 2023 8 1 88 105 10.1016/j.jacbts.2022.05.010 36777165
    [Google Scholar]
  80. Potential renoprotective effects and possible underlying mechanisms of angiotensin receptor-neprilysin inhibitors in cardiorenal syndrome. Front. Med. 2025 11
    [Google Scholar]
  81. Hobbs A.J. Moyes A.J. Baliga R.S. Ghedia D. Ochiel R. Sylvestre Y. Doré C.J. Chowdhury K. Maclagan K. Quartly H.L. Sofat R. Smit A. Schreiber B.E. Coghlan G.J. MacAllister R.J. Neprilysin inhibition for pulmonary arterial hypertension: A randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial. Br. J. Pharmacol. 2019 176 9 1251 1267 10.1111/bph.14621 30761523
    [Google Scholar]
  82. Zhang X. Hu C. Tian E. Shen Y. Liu W. Li J. Comprehensive review on neprilysin (NEP) inhibitors: Design, structure-activity relationships, and clinical applications. Front. Pharmacol. 2024 15 1501407 10.3389/fphar.2024.1501407 39764460
    [Google Scholar]
  83. AlAnazi F.H. Al-kuraishy H.M. Al-Gareeb A.I. Alexiou A. Papadakis M. Ogaly H.A. Alanazi Y.A. Saad H.M. Batiha G.E.S. Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena. J. Diabetes 2023 15 5 397 408 10.1111/1753‑0407.13389 37078106
    [Google Scholar]
  84. Grosso G. Godos J. Currenti W. Micek A. Falzone L. Libra M. Giampieri F. Forbes-Hernández T.Y. Quiles J.L. Battino M. La Vignera S. Galvano F. The effect of dietary polyphenols on vascular health and hypertension: Current evidence and mechanisms of action. Nutrients 2022 14 3 545 10.3390/nu14030545 35276904
    [Google Scholar]
  85. Inchingolo A.D. Inchingolo A.M. Malcangi G. Avantario P. Azzollini D. Buongiorno S. Viapiano F. Campanelli M. Ciocia A.M. De Leonardis N. de Ruvo E. Ferrara I. Garofoli G. Montenegro V. Netti A. Palmieri G. Mancini A. Patano A. Piras F. Marinelli G. Di Pede C. Laudadio C. Rapone B. Hazballa D. Corriero A. Fatone M.C. Palermo A. Lorusso F. Scarano A. Bordea I.R. Di Venere D. Inchingolo F. Dipalma G. Effects of resveratrol, curcumin and quercetin supplementation on bone metabolism—a systematic review. Nutrients 2022 14 17 3519 10.3390/nu14173519 36079777
    [Google Scholar]
  86. Mitra S. Lami M.S. Uddin T.M. Das R. Islam F. Anjum J. Hossain M.J. Emran T.B. Prospective multifunctional roles and pharmacological potential of dietary flavonoid narirutin. Biomed. Pharmacother. 2022 150 112932 10.1016/j.biopha.2022.112932 35413599
    [Google Scholar]
  87. Domínguez-Vías G. Segarra A.B. Ramírez-Sánchez M. Prieto I. Effects of virgin olive oil on blood pressure and renal aminopeptidase activities in male wistar rats. Int. J. Mol. Sci. 2021 22 10 5388 10.3390/ijms22105388 34065436
    [Google Scholar]
  88. Gál R. Halmosi R. Gallyas F. Tschida M. Mutirangura P. Tóth K. Alexy T. Czopf L. Resveratrol and beyond: The effect of natural polyphenols on the cardiovascular system: A narrative review. Biomedicines 2023 11 11 2888 10.3390/biomedicines11112888 38001889
    [Google Scholar]
  89. Socała K. Szopa A. Serefko A. Poleszak E. Wlaź P. Neuroprotective effects of coffee bioactive compounds: A review. Int. J. Mol. Sci. 2020 22 1 107 10.3390/ijms22010107 33374338
    [Google Scholar]
  90. Pérez-Torres I. Castrejón-Téllez V. Soto M.E. Rubio-Ruiz M.E. Manzano-Pech L. Guarner-Lans V. Oxidative stress, plant natural antioxidants, and obesity. Int. J. Mol. Sci. 2021 22 4 1786 10.3390/ijms22041786 33670130
    [Google Scholar]
  91. Panossian A.G. Efferth T. Shikov A.N. Pozharitskaya O.N. Kuchta K. Mukherjee P.K. Banerjee S. Heinrich M. Wu W. Guo D. Wagner H. Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐ and aging‐related diseases. Med. Res. Rev. 2021 41 1 630 703 10.1002/med.21743 33103257
    [Google Scholar]
  92. Kumari R. Pascalau R. Wang H. Bajpayi S. Yurgel M. Quansah K. Hattar S. Tampakakis E. Kuruvilla R. Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice. Cell Rep. 2024 43 2 113674 10.1016/j.celrep.2024.113674 38236776
    [Google Scholar]
  93. Liu Y. Sun J. Detection of pathogens and regulation of immunity by the caenorhabditis elegans nervous system. MBio 2021 12 2 e02301 e02320 10.1128/mBio.02301‑20
    [Google Scholar]
  94. Strehl C. Ehlers L. Gaber T. Buttgereit F. Glucocorticoids—All-rounders tackling the versatile players of the immune system. Front. Immunol. 2019 10 1744 10.3389/fimmu.2019.01744 31396235
    [Google Scholar]
  95. Anderson Z.T. Dawson A.D. Slominski A.T. Harris M.L. Current insights into the role of neuropeptide Y in skin physiology and pathology. Front. Endocrinol. 2022 13 838434 10.3389/fendo.2022.838434 35418942
    [Google Scholar]
  96. Kiaie N. Gorabi A.M. Reiner Ž. Jamialahmadi T. Ruscica M. Sahebkar A. Effects of statins on renin–angiotensin system. J. Cardiovasc. Dev. Dis. 2021 8 7 80 10.3390/jcdd8070080 34357323
    [Google Scholar]
  97. Sheng Y. Zhu L. The crosstalk between autonomic nervous system and blood vessels. Int. J. Physiol. Pathophysiol. Pharmacol. 2018 10 1 17 28
    [Google Scholar]
  98. Forte D. Krause D.S. Andreeff M. Bonnet D. Méndez-Ferrer S. Updates on the hematologic tumor microenvironment and its therapeutic targeting. Haematologica 2019 104 10 1928 1934 10.3324/haematol.2018.195396 31515356
    [Google Scholar]
  99. Langley D.B. Schofield P. Jackson J. Herzog H. Christ D. Crystal structures of human neuropeptide Y (NPY) and peptide YY (PYY). Neuropeptides 2022 92 102231 10.1016/j.npep.2022.102231 35180645
    [Google Scholar]
  100. Bahap-Kara M. Sariyildiz E. Yardimci G.K. Karadag O. Bayraktar-Ekincioglu A. Addressing glucocorticoid-related problems with the clinical pharmacist collaboration in rheumatology practice: A prospective follow-up study. Rheumatol. Ther. 2024 11 4 1043 1055 10.1007/s40744‑024‑00692‑z 38926304
    [Google Scholar]
  101. Reichardt S.D. Amouret A. Muzzi C. Vettorazzi S. Tuckermann J.P. Lühder F. Reichardt H.M. The role of glucocorticoids in inflammatory diseases. Cells 2021 10 11 2921 10.3390/cells10112921 34831143
    [Google Scholar]
  102. Wu J.Q. Jiang N. Yu B. Mechanisms of action of neuropeptide Y on stem cells and its potential applications in orthopaedic disorders. World J. Stem Cells 2020 12 9 986 1000 10.4252/wjsc.v12.i9.986 33033559
    [Google Scholar]
  103. Fattizzo B. Barcellini W. Autoimmune cytopenias in chronic lymphocytic leukemia: Focus on molecular aspects. Front. Oncol. 2020 9 1435 10.3389/fonc.2019.01435 31998632
    [Google Scholar]
  104. Galli S. Naranjo A. Van Ryn C. Tilan J.U. Trinh E. Yang C. Tsuei J. Hong S.H. Wang H. Izycka-Swieszewska E. Lee Y.C. Rodriguez O.C. Albanese C. Kitlinska J. Neuropeptide Y as a biomarker and therapeutic target for neuroblastoma. Am. J. Pathol. 2016 186 11 3040 3053 10.1016/j.ajpath.2016.07.019 27743558
    [Google Scholar]
  105. Chen W.C. Liu Y.B. Liu W.F. Zhou Y.Y. He H.F. Lin S. Neuropeptide Y is an immunomodulatory factor: Direct and indirect. Front. Immunol. 2020 ••• 11
    [Google Scholar]
  106. Chen Q.C. Zhang Y. The role of NPY in the regulation of bone metabolism. Front. Endocrinol. 2022 13 833485 10.3389/fendo.2022.833485 35273572
    [Google Scholar]
  107. Jeppsson S. Srinivasan S. Chandrasekharan B. Neuropeptide Y. Neuropeptide Y. NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation. Am. J. Physiol. Gastrointest. Liver Physiol. 2017 312 2 G103 G111 10.1152/ajpgi.00410.2015 27856419
    [Google Scholar]
  108. Chellappan D.K. Leng K.H. Jia L.J. Aziz N.A.B.A. Hoong W.C. Qian Y.C. Ling F.Y. Wei G.S. Ying T. Chellian J. Gupta G. Dua K. The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: A review. Biomed. Pharmacother. 2018 102 1127 1144 10.1016/j.biopha.2018.03.061 29710531
    [Google Scholar]
  109. Tilan J. Kitlinska J. Neuropeptide Y. Neuropeptide Y. NPY) in tumor growth and progression: Lessons learned from pediatric oncology. Neuropeptides 2016 55 55 66 10.1016/j.npep.2015.10.005 26549645
    [Google Scholar]
  110. Hao Z. Sadek I. Sunitinib: The antiangiogenic effects and beyond. OncoTargets Ther. 2016 9 5495 5505 10.2147/OTT.S112242 27660467
    [Google Scholar]
  111. Li Q. Geng S. Luo H. Wang W. Mo Y.Q. Luo Q. Wang L. Song G.B. Sheng J.P. Xu B. Signaling pathways involved in colorectal cancer: Pathogenesis and targeted therapy. Signal Transduct. Target. Ther. 2024 9 1 266 10.1038/s41392‑024‑01953‑7 39370455
    [Google Scholar]
  112. Mamun M.A.A. Rakib A. Mandal M. Kumar S. Singla B. Singh U.P. Polyphenols: Role in modulating immune function and obesity. Biomolecules 2024 14 2 221 10.3390/biom14020221 38397458
    [Google Scholar]
  113. Farhan M. Rizvi A. The pharmacological properties of red grape polyphenol resveratrol: Clinical trials and obstacles in drug development. Nutrients 2023 15 20 4486 10.3390/nu15204486 37892561
    [Google Scholar]
  114. Zoi V. Galani V. Lianos G.D. Voulgaris S. Kyritsis A.P. Alexiou G.A. The role of curcumin in cancer treatment. Biomedicines 2021 9 9 1086 10.3390/biomedicines9091086 34572272
    [Google Scholar]
  115. Kopustinskiene D.M. Jakstas V. Savickas A. Bernatoniene J. Flavonoids as anticancer agents. Nutrients 2020 12 2 457 10.3390/nu12020457 32059369
    [Google Scholar]
  116. Riaz M. Rahman N.U. Zia-Ul-Haq M. Jaffar H.Z.E. Manea R. Ginseng: A dietary supplement as immune-modulator in various diseases. Trends Food Sci. Technol. 2019 83 12 30 10.1016/j.tifs.2018.11.008
    [Google Scholar]
  117. Mokra D. Joskova M. Mokry J. Therapeutic effects of green tea polyphenol (‒)-epigallocatechin-3-gallate (egcg) in relation to molecular pathways controlling inflammation, oxidative stress, and apoptosis. Int. J. Mol. Sci. 2022 24 1 340 10.3390/ijms24010340 36613784
    [Google Scholar]
  118. Halim S.A. Khan A. Csuk R. Al-Rawahi A. Al-Harrasi A. Diterpenoids and triterpenoids from frankincense are excellent anti-psoriatic agents: An in silico Approach. Front Chem. 2020 8 486 10.3389/fchem.2020.00486 32671018
    [Google Scholar]
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