VIP 6 MG

Description

Vasoactive intestinal peptide (VIP), also known as vasoactive intestinal polypeptide or PHM27, is a short peptide hormone produced in the gut, pancreas, and brain of most vertebrate species, including humans. VIP primarily binds to class II G protein-coupled receptors and plays a critical role in numerous physiological processes, including:

• Promoting glycogen breakdown in the liver and muscle tissue
• Lowering blood pressure via vasodilation
• Relaxing smooth muscle throughout the gastrointestinal tract
• Enhancing cardiac muscle contraction and increasing heart rate
• Stimulating water secretion across various regions of the GI tract
• Influencing vaginal lubrication
• Modulating prolactin release
• Providing cartilage protection
• Protecting neurons from ischemic and oxidative damage
• Modulating autonomic nervous system activity
• Synchronizing the brain’s circadian rhythm center (the suprachiasmatic nucleus) with environmental light cues

Due to its wide-ranging physiological functions, VIP has remained a topic of intense scientific interest for decades. The breadth of available research is extensive, covering its systemic, neuroprotective, and immunoregulatory effects. Of particular significance is VIP’s ability to reduce inflammation and prevent fibrosis in multiple organ systems—an area of study that continues to hold immense therapeutic promise.

VIP Peptide Structure

Amino Acid Sequence: HSDAVFTDNYXRLRKQMAVKKYLNSXLN
Molecular Formula: C₁₄₇H₂₃₇N₄₃O₄₃S
Molecular Weight:
Human Gene: VIP; 6q25.2
PubChem CID: 44567960
CAS Number: 37221-79-7
Synonyms: VIP, PHM27, Vasoactive intestinal polypeptide

Source: PubChem

VIP Peptide Research

Bowel Inflammation

VIP is primarily produced by immune nerve fibers located in blood vessels of both the central and peripheral nervous systems, as well as the heart. Additionally, certain immune cells themselves generate VIP, where it promotes Th2-type immune responses that help suppress inflammation and regulate immune activity. Due to these properties, VIP and its analogues have been extensively studied as potential therapeutic agents for managing inflammation in intestinal disorders, cardiovascular disease, and neuroinflammatory conditions [1], [2].

The different functions of VIP in immunomodulation:

Source: Pharmacological Reviews

VIP and Inflammatory Bowel Disease

In inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis, VIP has demonstrated potential in improving intestinal barrier integrity and suppressing inflammation driven by Th1 cells [3]. Notably, VIP appears to stimulate T cells to produce interleukin-10, an anti-inflammatory peptide that plays a significant role in immune regulation [4]. Given that Th1-driven inflammation is only one of multiple key pathways in IBD, VIP’s targeted influence offers promising therapeutic value.

The restoration of intestinal barrier function is also a critical benefit of VIP. Impaired barrier integrity is hypothesized to contribute to IBD pathogenesis by allowing antigens to enter intercellular spaces and trigger immune responses. By reinforcing the barrier and limiting antigen exposure, VIP may interrupt one of the early steps in the cascade that leads to colitis and chronic inflammation [3].

VIP in Lung Function

VIP supports lung health through two primary mechanisms. First, it modulates pulmonary vascular remodeling by inhibiting NFAT (nuclear factor of activated T-cells), a key mediator of T cell activation and inflammation [5]. Through this anti-inflammatory pathway, VIP may help prevent pulmonary fibrosis, the end-stage of several inflammatory lung diseases including COPD and sarcoidosis [6].

Second, VIP has been shown to inhibit the proliferation of smooth muscle cells in lung tissue—a critical factor in conditions like long-standing, poorly controlled asthma [7]. These anti-proliferative effects could help mitigate airway remodeling caused by chronic inflammation.

Additionally, VIP has powerful vasodilatory effects in pulmonary arteries. It can lower pulmonary arterial pressure, enhance cardiac output, and improve oxygen saturation in venous blood [8]. These findings offer hope that VIP might serve as a therapeutic option for pulmonary hypertension and other vascular-related lung conditions.

VIP and Organ Transplants

One of the major challenges in transplantation is immune rejection. Even with the best donor-recipient matching, immune responses eventually damage or destroy transplanted organs. Current immunosuppressive drugs, while effective, come with significant side effects including increased infection risk and tissue fibrosis.

VIP may offer a more refined solution. It modulates dendritic cell (DC) function—key players in initiating immune responses. VIP reduces DC activation and proliferation, especially among DCs that promote immune responses, while preserving tolerogenic DCs that encourage immune acceptance [9]. This selective immunomodulation could reduce transplant rejection while avoiding the downsides of broad immunosuppression, potentially revolutionizing anti-rejection therapy.

VIP as a Neuroprotectant

VIP plays multiple roles in the central nervous system (CNS): as a neurotransmitter, a neurotrophic factor, and a neuroprotectant. It helps maintain the blood-brain barrier (BBB), a critical structure that protects neural tissue from harmful agents circulating in the blood [10]. Disruption of the BBB is implicated in conditions like multiple sclerosis, stroke, and encephalomyelitis.

In neurodegenerative diseases, VIP has shown considerable promise. It helps regulate beta-amyloid accumulation in mouse models of Alzheimer’s disease and exhibits protective effects in Parkinson’s disease [11], [12]. In the developing brain, VIP safeguards against white matter damage and promotes proper fatty acid myelination of neurons [13].

In Parkinson’s disease, VIP helps shift immune activity away from Th1-dominant inflammation toward Th2-mediated protection [14]. In Alzheimer’s disease (AD), reduced VIP activity and processing have been documented, with lower levels of VIP and its metabolites found in affected individuals [15], [16]. Animal studies demonstrate that VIP infusion can significantly reduce beta-amyloid accumulation, highlighting the peptide’s role in AD pathology.

These effects are largely mediated through VPAC1 and VPAC2 receptors, which, when activated, stimulate the release of key neurotrophic factors such as ADNP (activity-dependent neuroprotective protein) and BDNF (brain-derived neurotrophic factor). These proteins are essential for synaptic maintenance and astrocyte health.

Source: PubChem

VIP and Cardiac Fibrosis

Similar to its role in lung disease, VIP shows promise in addressing cardiac fibrosis—the final common pathway of many heart conditions. Cardiac fibrosis can lead to significant complications, including valve dysfunction, reduced myocardial contractility, impaired ventricular filling, and arrhythmias. In advanced cases, fibrosis becomes so extensive that heart transplantation is the only option to prevent fatal outcomes.

Historically, the primary goal of cardiac treatment has been to slow the progression of fibrosis and prevent further scarring. Common pharmacologic interventions—such as ACE inhibitors and angiotensin receptor blockers—offer some protection by limiting cardiac remodeling. However, these therapies rarely halt the process completely, and many patients still experience a gradual decline in cardiac function.

Encouragingly, recent studies in rat models have shown that VIP may not only delay the fibrotic process but actually reverse existing cardiac scarring. This regenerative effect appears to be driven in part by a significant suppression of angiotensinogen and angiotensin receptor type 1a expression—key components of the renin-angiotensin system [17]. Given that drugs targeting this pathway are already mainstays in fibrosis prevention, VIP’s more profound and potentially reparative influence represents a compelling avenue for future cardiovascular therapies.

Source: ScienceDirect

Vasoactive Intestinal Peptide and COVID-19

A notable recent development from researchers in Switzerland and the United States has highlighted the potential of a synthetic VIP analogue, aviptadil (also known as RLF-100), in treating severe pulmonary complications of COVID-19. Like its natural counterpart, aviptadil suppresses the production of pro-inflammatory cytokines, offering targeted anti-inflammatory effects in the lungs.

One of the key findings is aviptadil’s protective action on type II alveolar cells, the primary cells responsible for oxygen exchange. These cells are particularly vulnerable to SARS-CoV-2 infection. Early research suggests that aviptadil may prevent viral penetration into these cells, thereby reducing the likelihood of severe lung damage. Currently, phase 2/3 placebo-controlled clinical trials are underway to assess its efficacy in treating serious COVID-19 complications [18].

According to Dr. Jonathan Javitt, CEO of NeuroRx (a company working in partnership with the developers of aviptadil), rapid improvement has been observed in critically ill COVID-19 patients treated with RLF-100—even those on ventilators or ECMO. Notably, some patients have responded within just three days, including individuals with severe comorbidities. In emergency use outside the trial setting, aviptadil has shown a remarkable ability to inhibit viral replication and accelerate recovery, effects not yet seen with traditional antiviral drugs.

Summary: VIP’s Emerging Role in Modern Medicine

VIP belongs to a broader class of neuroendocrine peptides and exerts diverse biological effects across the central nervous system, gastrointestinal tract, pulmonary tissue, and immune system. It also plays essential roles in embryonic development and cell signaling.

Research continues to support VIP’s potent anti-inflammatory and anti-fibrotic properties. These actions are particularly beneficial in conditions such as:

• Neurodegenerative diseases
• Pulmonary fibrosis
• Inflammatory bowel disease
• Cardiac fibrosis

Its immune-regulatory effects are of increasing interest in treating chronic inflammation and fibrotic disease progression, which are often the root causes of long-term morbidity and mortality.

As the COVID-19 pandemic has shown, synthetic VIP analogues like aviptadil may offer novel therapeutic strategies not only for viral infections but for a variety of inflammatory and fibrotic conditions. The success of these treatments could pave the way for future FDA approvals and pharmaceutical innovations centered around VIP and its derivatives.

Research Use Only Disclaimer

VIP exhibits minimal side effects, with low oral and excellent subcutaneous bioavailability in mice. Note that per kilogram dosage in mice does not scale to humans. VIP available from Peptide Sciences is strictly for educational and scientific research purposes only. It is not for human consumption. Only purchase VIP if you are a licensed researcher.

Article Author

The above literature was researched, edited, and organized by Dr. E. Logan, M.D. Dr. Logan holds a doctorate from Case Western Reserve University School of Medicine and a B.S. in Molecular Biology.

Scientific Journal Author
Dr. Jonathan Javitt is a physician with a background in information technology, health economics, and public health. He graduated in 1978 with honors in Biochemistry from Princeton University and earned his M.D. at Cornell University Medical College. He was awarded a Kellogg Foundation Fellowship to attend the Harvard School of Public Health, where he earned an M.P.H. in Health Policy and Management. In 2015, he was honored as an Alumnus of Merit, the highest recognition given by Harvard University to graduates of the School of Public Health.

Dr. Javitt’s scientific publications have been cited by more than 17,000 researchers, and he is ranked among the top 1% of quoted scientists worldwide. At the Potomac Institute, he has led projects in biodefense, drug and device policy, and first responder preparedness. He has also served as a commissioned Presidential appointee in health care and biodefense roles.

Dr. Jonathan Javitt is referenced as one of the leading scientists involved in the research and development of Vasoactive Intestinal Peptide (VIP). This citation does not imply endorsement, advocacy, or affiliation of any kind with Peptide Sciences. The purpose of referencing Dr. Javitt is solely to acknowledge and credit the extensive research conducted by scientists studying this peptide. Dr. Jonathan Javitt is cited in [18] of the referenced sources.

References

1. E. Gonzalez-Rey and M. Delgado, “Role of vasoactive intestinal peptide in inflammation and autoimmunity,” Curr. Opin. Investig. Drugs Lond. Engl. 2000, vol. 6, no. 11, pp. 1116–1123, Nov. 2005.
2. M. Delgado, D. Pozo, and D. Ganea, “The Significance of Vasoactive Intestinal Peptide in Immunomodulation,” Pharmacol. Rev., vol. 56, no. 2, pp. 249–290, Jun. 2004, doi: 10.1124/pr.56.2.7.
3. S. Seo et al., “Vasoactive intestinal peptide decreases inflammation and tight junction disruption in experimental necrotizing enterocolitis,” J. Pediatr. Surg., vol. 54, no. 12, pp. 2520–2523, Dec. 2019, doi: 10.1016/j.jpedsurg.2019.08.038.
4. E. Gonzalez-Rey and M. Delgado, “Therapeutic treatment of experimental colitis with regulatory dendritic cells generated with vasoactive intestinal peptide,” Gastroenterology, vol. 131, no. 6, pp. 1799–1811, Dec. 2006, doi: 10.1053/j.gastro.2006.10.023.
5. S. I. Said, “The vasoactive intestinal peptide gene is a key modulator of pulmonary vascular remodeling and inflammation,” Ann. N. Y. Acad. Sci., vol. 1144, pp. 148–153, Nov. 2008, doi: 10.1196/annals.1418.014.
6. A. M. Szema et al., “NFATc3 and VIP in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease,” PloS One, vol. 12, no. 1, p. e0170606, 2017, doi: 10.1371/journal.pone.0170606.
7. “Vasoactive Intestinal Peptide – an overview | ScienceDirect Topics.” https://www.sciencedirect.com/topics/neuroscience/vasoactive-intestinal-peptide (accessed Jan. 01, 2021).
8. V. Petkov et al., “Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension,” J. Clin. Invest., vol. 111, no. 9, pp. 1339–1346, May 2003, doi: 10.1172/JCI17500.
9. A. Chorny, E. Gonzalez-Rey, and M. Delgado, “Regulation of dendritic cell differentiation by vasoactive intestinal peptide: therapeutic applications on autoimmunity and transplantation,” Ann. N. Y. Acad. Sci., vol. 1088, pp. 187–194, Nov. 2006, doi: 10.1196/annals.1366.004.
10. D. R. Staines, E. W. Brenu, and S. Marshall-Gradisnik, “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., vol. 5, pp. 81–89, 2009, Accessed: Jan. 01, 2021. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695238/.
11. F. R. O. de Souza, F. M. Ribeiro, and P. M. d’ Almeida Lima, “Implications of VIP and PACAP in Parkinson’s disease: what do we know so far?,” Curr. Med. Chem., Mar. 2020, doi: 10.2174/0929867327666200320162436.
12. O. T. Korkmaz et al., “Vasoactive Intestinal Peptide Decreases β-Amyloid Accumulation and Prevents Brain Atrophy in the 5xFAD Mouse Model of Alzheimer’s Disease,” J. Mol. Neurosci. MN, vol. 68, no. 3, pp. 389–396, Jul. 2019, doi: 10.1007/s12031-018-1226-8.
13. P. Gressens, L. Besse, P. Robberecht, I. Gozes, M. Fridkin, and P. Evrard, “Neuroprotection of the developing brain by systemic administration of vasoactive intestinal peptide derivatives,” J. Pharmacol. Exp. Ther., vol. 288, no. 3, pp. 1207–1213, Mar. 1999.
14. R. L. Mosley et al., “A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson’s Disease,” Front. Cell. Neurosci., vol. 13, p. 421, 2019, doi: 10.3389/fncel.2019.00421.
15. M. Yasuda, K. Maeda, T. Kakigi, N. Minamitani, T. Kawaguchi, and C. Tanaka, “Low cerebrospinal fluid concentrations of peptide histidine valine and somatostatin-28 in Alzheimer’s disease: altered processing of prepro-vasoactive intestinal peptide and prepro-somatostatin,” Neuropeptides, vol. 29, no. 6, pp. 325–330, Dec. 1995, doi: 10.1016/0143-4179(95)90003-9.
16. R. H. Perry, G. J. Dockray, R. Dimaline, E. K. Perry, G. Blessed, and B. E. Tomlinson, “Neuropeptides in Alzheimer’s disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex,” J. Neurol. Sci., vol. 51, no. 3, pp. 465–472, Sep. 1981, doi: 10.1016/0022-510x(81)90123-4.
17. K. A. Duggan, G. Hodge, J. Chen, and T. Hunter, “Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat,” Eur. J. Pharmacol., vol. 862, p. 172629, Nov. 2019, doi: 10.1016/j.ejphar.2019.172629.
18. C. Smith, BGR, Aug. 03, 2020. https://bgr.com/2020/08/03/coronavirus-cure-rlf-100-aviptadil-phase-3-trial/ (accessed Jan. 01, 2021).

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