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Vasoactive Intestinal Peptide

Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) is a peptide hormone of 28 amino acids. It is found in the intestines, pancreas, and central nervous system. It is involved in various important bodily functions such as heart contraction, blood circulation, energy production, blood pressure regulation, and smooth muscle relaxation.

Overall Health Benefits

  • Lowers risk of heart disease [1-6]
  • Promotes healthy lungs [7-12]
  • Promotes wound healing [13-17]
  • Regulates blood pressure [18-20]
  • Promotes a healthy digestive system [21-24]
  • Prevents cancer [25-28]
  • Boosts immunity [29-31]
  • Improves mental health [32-33]

Proven Health Benefits

Lowers Risk of Heart Disease

Numerous studies support the beneficial effects of VIP on the cardiovascular system:

  1. A study showed that VIP is important for maintaining normal blood flow to the heart. [1]
  2. In patients with heart failure (HF) due to dilated cardiomyopathy, increased VIP levels in the blood were associated with restoration of blood flow. [2]
  3. A study showed that low concentration of VIP was associated with a higher risk of coronary disease. [3]
  4. In mouse models, injection of VIP reduced injury from myocarditis (heart muscle inflammation) and decreased the number and size of plaques caused by atherosclerosis. [4]
  5. A study reported that combined administration of VIP and pituitary adenylate cyclase-activating peptide (PACAP) protected against heart disease. [5]
  6. In patients with HF, decreased concentration of VIP led to worsening of symptoms while increased levels improved blood flow to the heart. [6]

Promotes Healthy Lungs

VIP has also been shown to exert beneficial effects on lung health:

  1. A study found that VIP can help improve lung function and protect against pulmonary disorders. [7]
  2. In patients with pulmonary sarcoidosis (lung inflammation and scarring), VIP inhalation through nebulizer produced anti-inflammatory effects. [8]
  3. A study found that VIP-based agents can be used in the treatment of various pulmonary diseases. [9]
  4. A review of several studies presented the potential role of inhaled VIP as an alternative drug for lung disease. [10]
  5. A study showed that VIP’s anti-inflammatory effects could play a role in treating asthma, pulmonary arterial hypertension, and chronic obstructive pulmonary disease. [11]
  6. A study reported that VIP decreased cell injury induced by high oxygen levels, which in turn reduced the progression of lung impairment. [12]

Promotes Wound Healing

Studies also support the regenerative properties of VIP:

  1. In human bronchial epithelial cells (HBEC), VIP produced protective effects against cell damage and promoted wound recovery. [13]
  2. In rabbits, VIP injection accelerated the healing of alkali-induced corneal burns. [14]
  3. In mice, VIP-coated wound dressings were effective in promoting wound healing by stimulating tissue and blood vessel growth. [15]
  4. In diabetic mice, VIP boosted wound healing by regulating inflammation and nerve regeneration. [16]
  5. In mice, VIP treatment has been shown to increase the survival rate of the transplanted cornea. [17]

Regulates Blood Pressure

Evidence also suggests that VIP has antihypertensive effects:

  1. In hamsters, the administration of encapsulated VIP was effective in lowering blood pressure. [18]
  2. In healthy patients, VIP’s blood vessel-dilating properties lowered systemic blood pressure. [19]
  3. In cats, VIP increased blood flow while lowering blood pressure. [20]

Promotes a Healthy Digestive System

Studies suggest that VIP is essential for a healthy gut:

  1. In mice, VIP maintained microbiota balance in the digestive system. [21]
  2. A study suggested that VIP plays a significant role in the excretion of body fat. [22]
  3. Studies also reported that VIP can help improve gastrointestinal function by increasing blood flow to the different structures in the gut and regulating the secretion of gastric acid. [23-24]

Prevents Cancer

VIP can also combat various types of cancer:

  1. A study showed that VIP prevents cancer progression by controlling cell migration. [25]
  2. A study found that VIP has a tumor-regressing effect against gastrointestinal cancers. [26]
  3. In breast cancer cells, VIP inhibited the growth and multiplication of cancer cells. [27-28]

Boosts Immunity

Studies show that VIP has beneficial effects on the immune function:

  1. In animal studies, VIP showed great therapeutic potential against inflammatory diseases. [29]
  2. A study suggested that VIP modulates the body’s immune tolerance by regulating the balance between pro-inflammatory and anti-inflammatory substances. [30]
  3. In murine cytomegalovirus (mCMV) infected mice, VIP injection significantly increased the survival rates of the subjects by enhancing their innate and adaptive cellular immunity. [31]

Improves Mental Health

VIP also plays a role in maintaining good mental health:

  1. A review of several studies discussed the potential therapeutic role of VIP in treating neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and Autism spectrum disorders. [32]
  2. A study reported that VIP exerts its neuroprotective effects by inhibiting the loss of neurons in the brain. [33]

References:

  1. Henning RJ, Sawmiller DR. Vasoactive intestinal peptide: cardiovascular effects. Cardiovasc Res. 2001 Jan;49(1):27-37. doi: 10.1016/s0008-6363(00)00229-7. PMID: 11121793.
  2. Lucia P, Caiola S, Coppola A, Manetti LL, Maroccia E, De Martinis C, Buongiorno AM. Il peptide vasoattivo intestinale nello scompenso cardiaco [Vasoactive intestinal peptide in heart failure]. Ital Heart J Suppl. 2000 May;1(5):679-85. Italian. PMID: 10834134.
  3. Unverferth DV, O’Dorisio TM, Miller MM, Uretsky BF, Magorien RD, Leier CV, Thompson ME, Hamlin RL. Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure. J Lab Clin Med. 1986 Jul;108(1):11-6. PMID: 3711722.
  4. Benitez R, Delgado-Maroto V, Caro M, Forte-Lago I, Duran-Prado M, O’Valle F, Lichtman AH, Gonzalez-Rey E, Delgado M. Vasoactive Intestinal Peptide Ameliorates Acute Myocarditis and Atherosclerosis by Regulating Inflammatory and Autoimmune Responses. J Immunol. 2018 Jun 1;200(11):3697-3710. doi: 10.4049/jimmunol.1800122. Epub 2018 Apr 18. PMID: 29669783.
  5. Dvoráková MC. Cardioprotective role of the VIP signaling system. Drug News Perspect. 2005 Jul-Aug;18(6):387-91. doi: 10.1358/dnp.2005.18.6.927930. PMID: 16247516.
  6. Lucia P, Caiola S, Coppola A, Manetti LL, Maroccia E, Buongiorno AM, De Martinis C. Vasoactive intestinal peptide (VIP): a new neuroendocrine marker of clinical progression in chronic heart failure? Clin Endocrinol (Oxf). 2003 Dec;59(6):723-7. doi: 10.1046/j.1365-2265.2003.01913.x. PMID: 14974913.
  7. Said SI. Vasoactive peptides in the lung, with special reference to vasoactive intestinal peptide. Exp Lung Res. 1982 Nov;3(3-4):343-8. doi: 10.3109/01902148209069662. PMID: 6762962.
  8. Available at https://www.atsjournals.org/doi/full/10.1164/rccm.200909-1451OC.
  9. Wu D, Lee D, Sung YK. Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review. Respir Res. 2011 Apr 11;12(1):45. doi: 10.1186/1465-9921-12-45. PMID: 21477377; PMCID: PMC3090995.
  10. Mathioudakis A, Chatzimavridou-Grigoriadou V, Evangelopoulou E, Mathioudakis G. Vasoactive intestinal Peptide inhaled agonists: potential role in respiratory therapeutics. Hippokratia. 2013;17(1):12-16.
  11. Wu D, Lee D, Sung YK. Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review. Respir Res. 2011;12(1):45. Published 2011 Apr 11. doi:10.1186/1465-9921-12-45.
  12. Ao X, Fang F, Xu F. Vasoactive intestinal peptide protects alveolar epithelial cells against hyperoxia via promoting the activation of STAT3. Regul Pept. 2011 Jun 7;168(1-3):1-4. doi: 10.1016/j.regpep.2011.02.006. Epub 2011 Feb 18. PMID: 21334383.
  13. Guan CX, Zhang M, Qin XQ, Cui YR, Luo ZQ, Bai HB, Fang X. Vasoactive intestinal peptide enhances wound healing and proliferation of human bronchial epithelial cells. Peptides. 2006 Dec;27(12):3107-14. doi: 10.1016/j.peptides.2006.08.004. Epub 2006 Sep 11. PMID: 16965837.
  14. Tuncel N, Yildirim N, Gurer F, Basmak H, Uzuner K, Sahinturk V, Gursoy H. Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas. Int J Ophthalmol. 2016 Feb 18;9(2):204-10. doi: 10.18240/ijo.2016.02.04. PMID: 26949636; PMCID: PMC4761728.
  15. Wang Y, Chen Z, Luo G, He W, Xu K, Xu R, Lei Q, Tan J, Wu J, Xing M. In-Situ-Generated Vasoactive Intestinal Peptide Loaded Microspheres in Mussel-Inspired Polycaprolactone Nanosheets Creating Spatiotemporal Releasing Microenvironment to Promote Wound Healing and Angiogenesis. ACS Appl Mater Interfaces. 2016 Mar 23;8(11):7411-21. doi: 10.1021/acsami.5b11332. Epub 2016 Mar 14. PMID: 26914154.
  16. Zhang Y, Gao N, Wu L, Lee PSY, Me R, Dai C, Xie L, Yu FX. Role of VIP and Sonic Hedgehog Signaling Pathways in Mediating Epithelial Wound Healing, Sensory Nerve Regeneration, and Their Defects in Diabetic Corneas. Diabetes. 2020 Jul;69(7):1549-1561. doi: 10.2337/db19-0870. Epub 2020 Apr 28. PMID: 32345752; PMCID: PMC7306128.
  17. Satitpitakul V, Sun Z, Suri K, Amouzegar A, Katikireddy KR, Jurkunas UV, Kheirkhah A, Dana R. Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival. Am J Pathol. 2018 Sep;188(9):2016-2024. doi: 10.1016/j.ajpath.2018.05.010. Epub 2018 Aug 7. PMID: 30097165; PMCID: PMC6593256.
  18. Gao XP, Noda Y, Rubinstein I, Paul S. Vasoactive intestinal peptide encapsulated in liposomes: effects on systemic arterial blood pressure. Life Sci. 1994;54(15):PL247-52. doi: 10.1016/0024-3205(94)00425-0. PMID: 8152324.
  19. Eriksson LS, Hagenfeldt L, Mutt V, Wahren J. Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects. Peptides. 1989 Mar-Apr;10(2):481-4. doi: 10.1016/0196-9781(89)90062-4. PMID: 2666962.
  20. Eklund S, Jodal M, Lundgren O, Sjöqvist A. Effects of vasoactive intestinal polypeptide on blood flow, motility and fluid transport in the gastrointestinal tract of the cat. Acta Physiol Scand. 1979 Apr;105(4):461-8. doi: 10.1111/j.1748-1716.1979.tb00111.x. PMID: 452923.
  21. Bains M, Laney C, Wolfe AE, Orr M, Waschek JA, Ericsson AC, Dorsam GP. Vasoactive Intestinal Peptide Deficiency Is Associated With Altered Gut Microbiota Communities in Male and Female C57BL/6 Mice. Front Microbiol. 2019 Dec 2;10:2689. doi: 10.3389/fmicb.2019.02689. PMID: 31849864; PMCID: PMC6900961.
  22. Vu JP, Larauche M, Flores M, Luong L, Norris J, Oh S, Liang LJ, Waschek J, Pisegna JR, Germano PM. Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP). J Mol Neurosci. 2015 Jun;56(2):377-87. doi: 10.1007/s12031-015-0556-z. Epub 2015 Apr 23. PMID: 25904310; PMCID: PMC4458420.
  23. Zimmerman RP, Gates TS, Mantyh CR, Vigna SR, Welton ML, Passaro EP Jr, Mantyh PW. Vasoactive intestinal polypeptide receptor binding sites in the human gastrointestinal tract: localization by autoradiography. Neuroscience. 1989;31(3):771-83. doi: 10.1016/0306-4522(89)90440-5. PMID: 2556662.
  24. Said SI. Vasoactive intestinal peptide in the gut. Physiology and pathology. Acta Gastroenterol Belg. 1982 Jul-Aug;45(7-8):310-3. PMID: 6301189.
  25. Cochaud S, Chevrier L, Meunier AC, Brillet T, Chadéneau C, Muller JM. The vasoactive intestinal peptide-receptor system is involved in human glioblastoma cell migration. Neuropeptides. 2010 Oct;44(5):373-83. doi: 10.1016/j.npep.2010.06.003. Epub 2010 Jul 17. PMID: 20638719.
  26. Jaggi M, Prasad S, Singh AT, Praveen R, Dutt S, Mathur A, Sharma R, Gupta N, Ahuja R, Mukherjee R, Burman AC. Anticancer activity of a peptide combination in gastrointestinal cancers targeting multiple neuropeptide receptors. Invest New Drugs. 2008 Dec;26(6):489-504. doi: 10.1007/s10637-008-9117-4. Epub 2008 Jan 24. PMID: 18217205.
  27. Said SI. Vasoactive intestinal peptide in the gut. Physiology and pathology. Acta Gastroenterol Belg. 1982 Jul-Aug;45(7-8):310-3. PMID: 6301189.Moody TW, Mantey SA, Fuselier JA, Coy DH, Jensen RT. Vasoactive intestinal peptide-camptothecin conjugates inhibit the proliferation of breast cancer cells. Peptides. 2007 Sep;28(9):1883-90. doi: 10.1016/j.peptides.2007.04.017. Epub 2007 May 6. PMID: 17580098; PMCID: PMC2742204.
  28. Iwasaki M, Akiba Y, Kaunitz JD. Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system. F1000Res. 2019 Sep 12;8:F1000 Faculty Rev-1629. doi: 10.12688/f1000research.18039.1. PMID: 31559013; PMCID: PMC6743256.
  29. Smalley SG, Barrow PA, Foster N. Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its therapeutic potential in inflammatory disease. Clin Exp Immunol. 2009;157(2):225-234. doi:10.1111/j.1365-2249.2009.03956.x.
  30. Gonzalez-Rey E, Anderson P, Delgado M. Emerging roles of vasoactive intestinal peptide: a new approach for autoimmune therapy. Ann Rheum Dis. 2007;66 Suppl 3(Suppl 3):iii70-iii76. doi:10.1136/ard.2007.078519.
  31. Li JM, Darlak KA, Southerland L, Hossain MS, Jaye DL, Josephson CD, Rosenthal H, Waller EK. VIPhyb, an antagonist of vasoactive intestinal peptide receptor, enhances cellular antiviral immunity in murine cytomegalovirus infected mice. PLoS One. 2013 May 27;8(5):e63381. doi: 10.1371/journal.pone.0063381. PMID: 23723978; PMCID: PMC3664580.
  32. White CM, Ji S, Cai H, Maudsley S, Martin B. Therapeutic potential of vasoactive intestinal peptide and its receptors in neurological disorders. CNS Neurol Disord Drug Targets. 2010;9(5):661-666. doi:10.2174/187152710793361595.
  33. Deng G, Jin L. The effects of vasoactive intestinal peptide in neurodegenerative disorders. Neurol Res. 2017 Jan;39(1):65-72. doi: 10.1080/01616412.2016.1250458. Epub 2016 Oct 27. PMID: 27786097.

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