VIP (6mg) – Anti-Inflammatory & Neuroprotective Peptide

Description

VIP Peptide

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid peptide hormone naturally present in both the central and peripheral nervous systems.(1) Its widespread distribution has led researchers to explore its broad biological relevance, with proposed roles in neurotransmission, vasodilation, immune regulation, and secretory activity.(1)

Due to its potential involvement in a variety of physiological pathways, VIP has become a subject of significant interest in scientific research. Investigators continue to examine its possible role in neuromodulation and neurotransmission, as well as its broader relevance in diverse experimental contexts.(2)(3)

Overview

VIP is believed to exert its effects through interaction with three G protein-coupled receptors: VPAC1, VPAC2, and PAC1. Once bound, these receptors may trigger the adenylate cyclase pathway, an important signaling mechanism associated with a range of biological responses.(4)

One of the key differences among these receptors lies in their distribution throughout the body. VPAC1 is reported to be expressed primarily in the brain and in peripheral tissues such as the liver, lungs, intestines, and immune cells. VPAC2 is found in the central nervous system as well as in organs including the pancreas, heart, kidneys, skeletal muscles, gastrointestinal tract, and reproductive tissues. PAC1 is most prominently expressed in the brain and adrenal regions.(4)

This broad receptor distribution suggests that VIP may have diverse research implications across both central and peripheral systems, with its effects potentially varying according to receptor subtype and tissue location. You may also be interested in our related research peptides, including GHRP 2 Peptide, Fragment 176-191, Follistatin 344, LL-37 Peptide, Melanotan 2 Peptide, CJC-1295 DAC Peptide, Adipotide Peptide, MGF peptide, PEG-MGF Peptide, and Vilon Peptide.

Chemical Makeup

Molecular Formula: C₁₄₇H₂₃₇N₄₃O₄₃S
Molecular Weight: 3326.8 g/mol
Other Known Titles: PHM27, Vasoactive intestinal polypeptide

Research and Clinical Studies on VIP Peptide

VIP Peptide and Inflammation

Research has indicated that Vasoactive Intestinal Peptide (VIP), which is produced by immune cells themselves, may play an important role in maintaining immune system equilibrium. Several studies suggest that VIP exhibits potential anti-inflammatory properties in both innate (hereditary) and adaptive (acquired) immunity. In innate immunity, VIP is thought to inhibit the synthesis of inflammatory molecules such as cytokines and chemokines. In adaptive immunity, VIP may suppress the activity of inflammatory Th1-type cells while promoting Th2-type cell responses. This modulation of Th1-type inflammation suggests that VIP may contribute to improved intestinal immunity and a reduction in inflammation.(5)(6)

One particular study investigated the potential interactions between VIP and inflammation in the context of necrotizing enterocolitis (NEC), using murine models. The research found that VIP could help regulate intestinal epithelial barrier integrity and homeostasis. In this study, decreased expression of VIP-ergic neurons in the ileum of NEC-affected mice was linked to increased inflammation and compromised barrier function. The experimental models were exposed to NEC between postnatal days 5 and 9, and researchers measured NEC severity, intestinal inflammation markers (such as IL-6 and TNFα), and the expression of tight junction proteins like Claudin-3. The results indicated that VIP mRNA expression and immunoactivity were significantly reduced in NEC models compared to controls. Interestingly, exogenous VIP administration reduced the severity of NEC and lowered the levels of pro-inflammatory cytokines (IL-6 and TNFα) in the NEC + VIP group. Additionally, VIP treatment improved Claudin-3 expression, which is vital for tight junction function and intestinal barrier integrity, suggesting that VIP may help preserve barrier function in inflammatory conditions.

VIP Peptide and the Blood-Brain Barrier

The blood-brain barrier (BBB) and blood-spinal barrier (BSB) are essential components of the central nervous system, providing protection for brain and spinal cord tissues while regulating what substances can enter the bloodstream. Compromising the integrity of these barriers can have severe physiological consequences. Research has suggested that VIP might have neuroprotective properties that help maintain the integrity of the BBB and BSB.(9)

VIP is thought to influence several processes, including neurotransmission, vasodilation, and immune modulation. By activating adenylate cyclase (AC), VIP likely plays a key role in the production of cyclic adenosine monophosphate (cAMP), a molecule that regulates immune responses, including those involving regulatory T cells (Tregs). When autoimmune reactions target VIP or its receptors, the permeability of the BBB and BSB may increase, a phenomenon referred to as “leakiness,” potentially contributing to neuroinflammatory and neurodegenerative conditions. Research into the Virchow-Robin spaces (VRS)—perivascular areas surrounding small blood vessels in the central nervous system—suggests that these regions may contain VIP receptors and be involved in immune modulation. Autoimmune responses targeting VIP receptors in these areas could impair BBB and BSB function, further highlighting the potential role of VIP in preserving the integrity of these barriers. This is an ongoing area of investigation, particularly in experimental models of neurodegeneration.(10)(11)

VIP Peptide and Cardiac Fibrosis

Cardiac fibrosis is a pathophysiological condition associated with increased expression of angiotensinogen receptors and angiotensin-converting enzymes (ACE), both of which contribute to vascular inflammation. Recent studies have suggested that VIP may help reduce the expression of angiotensinogen, similar to the action of ACE inhibitors, potentially mitigating cardiac fibrosis and reversing heart muscle scarring.(12)

In one experiment, VIP was administered to murine models on a high-salt diet to assess its effects on myocardial VIP levels, fibrosis, and pro-fibrotic mediators. The findings revealed that VIP-treated mice exhibited significantly higher myocardial VIP levels and lower fibrosis compared to control animals. Notably, the study observed reduced expression of angiotensinogen (Agt) and angiotensin receptor type 1a (AT1a), suggesting that VIP may downregulate the renin-angiotensin system, a key pathway involved in fibrotic processes. Despite these promising findings, not all pro-fibrotic mediators were affected by VIP, with factors like TGFβ, TNFα, CTGF, and NFκB showing no significant change. These results imply that the anti-fibrotic effects of VIP may be selective, possibly acting through alternative, unexplored pathways.

VIP and Behavioral Responses in Animals

Studies have suggested that VIP neurons play a role in modulating behavioral responses in animals. Specifically, activation of VIP neurons in the hypothalamus may trigger prolactin hormone secretion, which is linked to behaviors such as affiliation, gregariousness, pair bonding, and aggression. VIP and its associated VPAC receptors are distributed across both hypothalamic and extrahypothalamic regions, indicating that VIP may influence various behavioral and reproductive functions.

VIP’s effect on prolactin (PRL) secretion appears to be particularly important for reproductive behaviors, as changes in VIP levels within the hypothalamus correspond to fluctuations in plasma PRL levels across different reproductive stages. This suggests that VIP may play a role in behaviors related to offspring care. Additionally, VIP is involved in circadian rhythm regulation, particularly in the suprachiasmatic nucleus (SCN), where it modulates the activity of GABAergic cells. This influence on biological rhythms may affect ovulation timing and responses to photoperiod changes, which are crucial for understanding seasonal reproduction in mammals and birds.

Moreover, VIP’s interactions with other neuropeptides, including oxytocin and vasopressin, may modulate social behaviors such as aggression and pair bonding. Studies have shown that altering VIP levels in the hypothalamus can influence aggressive behaviors in certain avian species, potentially through its interaction with signaling molecules that regulate aggression. The full extent of VIP’s role in behavioral responses remains under investigation, but its influence on social dynamics and responses to stressors continues to be a compelling area of research.

VIP peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References:

1. Delgado, M., & Ganea, D. (2013). Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino acids, 45(1), 25–39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883350/
2. Iwasaki, M., Akiba, Y., & Kaunitz, J. D. (2019). Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system. F1000Research, 8, F1000 Faculty Rev-1629. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743256/
3. Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010). Suprachiasmatic nucleus: cell autonomy and network properties. Annual review of physiology, 72, 551–577. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758475/
4. Vosko, A. M., Schroeder, A., Loh, D. H., & Colwell, C. S. (2007). Vasoactive intestinal peptide and the mammalian circadian system. General and comparative endocrinology, 152(2-3), 165–175. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994114/
5. Gonzalez-Rey E, Delgado M. Role of vasoactive intestinal peptide in inflammation and autoimmunity. Curr Opin Investig Drugs. 2005 Nov;6(11):1116-23. https://pubmed.ncbi.nlm.nih.gov/16312132/
6. Seo S, Miyake H, Alganabi M, Janssen Lok M, O’Connell JS, Lee C, Li B, Pierro A. Vasoactive intestinal peptide decreases inflammation and tight junction disruption in experimental necrotizing enterocolitis. https://pubmed.ncbi.nlm.nih.gov/31668399/
7. Chorny A, Gonzalez-Rey E, Delgado M. Regulation of dendritic cell differentiation by vasoactive intestinal peptide: therapeutic applications on autoimmunity and transplantation. Ann N Y Acad Sci. 2006 Nov;1088:187-94. https://pubmed.ncbi.nlm.nih.gov/17192565/
8. Chorny, A., Gonzalez-Rey, E., Fernandez-Martin, A., Pozo, D., Ganea, D., & Delgado, M. (2005). Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders. Proceedings of the National Academy of Sciences of the United States of America, 102(38), 13562–13567. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1224633/
9. Staines DR, Brenu EW, Marshall-Gradisnik S. Postulated vasoactive neuropeptide immunopathology affecting the blood-brain/blood-spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment? Neuropsychiatr Dis Treat. 2009;5:81-9. Epub 2009 Apr 8. PMID: 19557103; PMCID: PMC2695238. https://pubmed.ncbi.nlm.nih.gov/19557103/
10. Mosley RL, Lu Y, Olson KE, Machhi J, Yan W, Namminga KL, Smith JR, Shandler SJ, Gendelman HE. A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson’s Disease. Front Cell Neurosci. 2019 Sep 18;13:421. https://pubmed.ncbi.nlm.nih.gov/31619964/
11. Solés-Tarrés, I., Cabezas-Llobet, N., Vaudry, D., & Xifró, X. (2020). Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Against Cognitive Decline in Neurodegenerative Diseases. Frontiers in cellular neuroscience, 14, 221. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380167/
12. Karen A. Duggan, George Hodge, Juchuan Chen, Tegan Hunter, Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat, European Journal of Pharmacology, Volume 862, 2019, 172629, ISSN 0014-2999. https://www.sciencedirect.com/science/article/pii/S0014299919305813
13. Kingsbury MA. New perspectives on vasoactive intestinal polypeptide as a widespread modulator of social behavior. Curr Opin Behav Sci. 2015 Dec 1;6:139-147. https://pubmed.ncbi.nlm.nih.gov/26858968/
14. Domschke, S., Domschke, W., Bloom, S. R., Mitznegg, P., Mitchell, S. J., Lux, G., & Strunz, U. (1978). Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut, 19(11), 1049–1053. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412244/