Cognitive & Longevity Research

VIP
Vasoactive Intestinal Peptide

VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide found throughout the CNS, gut, immune system, and autonomic nervous system. Originally named for its vasodilatory properties, VIP is now understood as a master regulator of circadian rhythm, inflammation, and gut-brain axis signaling — with emerging clinical research in autoimmune and inflammatory conditions.

NeuropeptideAnti-InflammatoryCircadianGut-Brain AxisImmunomodulatoryVasodilatory

At a Glance

CAS Number
37221-79-7
Molecular Weight
3,326.8 Da
Amino Acids
28 Amino Acids
Published Studies
Substantial preclinical + clinical
Stability
High — lyophilized stable
Research Status
Active research; clinical trials in inflammatory conditions
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Overview

VIP acts on two receptor subtypes — VPAC1 and VPAC2 — which are expressed across nearly every tissue type. This broad receptor distribution explains VIP's involvement in seemingly disparate functions: circadian clock synchronization in the suprachiasmatic nucleus, anti-inflammatory cytokine modulation in immune tissue, vasodilation in pulmonary vasculature, and gut motility regulation.

Its role as the master synchronizer of the circadian clock's inter-cellular communication has generated substantial interest in chronobiology research — VIP is the signal that keeps individual SCN neurons in synchrony.

"VIP is one of the most multifunctional neuropeptides in the body — circadian clock signal, anti-inflammatory mediator, gut-brain axis regulator, and vasodilator all in one 28-amino-acid package. Its clinical research is finally catching up with the preclinical interest."

Phase 2 clinical trials in rheumatoid arthritis and ARDS have generated human safety and preliminary efficacy data — establishing clinical relevance beyond the extensive preclinical literature.

Mechanism of Action

This compound operates through several converging biological pathways, which helps explain the breadth of effects observed across different tissue and metabolic models.

Circadian Clock Synchronization

Acts as the inter-neuronal synchronization signal in the SCN (suprachiasmatic nucleus) — keeping individual clock neurons in phase to maintain coherent circadian output.

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Anti-Inflammatory Immunomodulation

Binds VPAC1/2 on immune cells to shift macrophage polarization toward anti-inflammatory M2 phenotype and reduce pro-inflammatory cytokine release.

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Pulmonary Vasodilation

Strong vasodilatory effects in pulmonary vasculature — studied in pulmonary arterial hypertension and ARDS models.

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Gut-Brain Axis Signaling

Produced by enteric neurons and regulates gut motility, secretion, and gut-immune-brain communication — a key gut-brain axis signaling molecule.

Key Research Areas

Preclinical and clinical models have investigated this compound across a wide range of physiological contexts and tissue types.

  • Circadian rhythm research — SCN synchronization and jet lag/shift work models
  • Autoimmune disease — rheumatoid arthritis Phase 2 trials
  • ARDS and pulmonary hypertension — vasodilatory and anti-inflammatory dual mechanism
  • Gut-brain axis — enteric nervous system communication and gut motility
  • Inflammatory bowel disease — gut immune modulation
  • Neuroinflammation — CNS anti-inflammatory signaling
  • Sepsis models — immune modulation in systemic inflammation

VIP's position at the intersection of circadian biology, immunology, and gut-brain axis research makes it one of the most multifunctional — and most under-recognized — research peptides available.

Compound Comparison

VIP, DSIP, and Selank each address different dimensions of CNS and immune research — with VIP uniquely positioned across both circadian and inflammatory biology.

Aspect VIP DSIP Selank
Primary CNS Role Circadian synchronization Delta sleep induction Anxiolytic, anti-inflammatory
Immune Effects Strong anti-inflammatory (VPAC) HPA normalization Tuftsin-derived immune modulation
Peripheral Action Vasodilation, gut motility Minimal Minimal
Clinical Data Phase 2 (RA, ARDS) Small clinical trials Russian clinical data
Best Research Use Circadian, autoimmune, ARDS Sleep architecture Anxiety, immune
Safety Profile in Research Studies

The following reflects findings from published preclinical and clinical safety assessments where available.


Phase 2 clinical data in autoimmune and ARDS conditions — human evidence beyond preclinical


Multisystem research utility — circadian, immune, gut, and vascular research in one compound


Endogenous neuropeptide — acts through its natural receptor system; fundamental safety profile


Short half-life — rapidly degraded; research protocols require careful timing or modified delivery systems

Frequently Asked Questions
What does VIP do in the gut?
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VIP is produced by enteric neurons throughout the gastrointestinal tract. It relaxes smooth muscle, stimulates intestinal secretion, and modulates gut immune cells. It's a key neurotransmitter in the enteric nervous system and a gut-brain axis signaling molecule.
How does VIP synchronize the circadian clock?
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Individual neurons in the suprachiasmatic nucleus (SCN) each have their own circadian oscillator. VIP is the inter-neuronal signal that keeps them synchronized — without it, SCN neurons fall out of phase with each other and circadian output becomes incoherent. This makes VIP essential for normal circadian function.
What were the rheumatoid arthritis trial results?
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Phase 2 trials showed VIP reduced clinical disease activity scores and pro-inflammatory cytokines in RA patients. The anti-inflammatory mechanism — shifting macrophages toward M2 phenotype and reducing TNF-α — was confirmed in human tissue samples from trial participants.
Is VIP relevant to COVID/ARDS research?
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Yes — VIP's pulmonary vasodilatory and anti-inflammatory properties led to clinical trials in ARDS, including COVID-19-associated ARDS. Preliminary data showed improvements in oxygenation in severely ill patients; larger trials are ongoing.

This overview is strictly educational and based on publicly available scientific literature as of 2026. It does not constitute medical advice. All Helixera Labs products are for laboratory research use only. Not for human or veterinary use. · Helixera Labs LLC © 2026