Vasoactive Intestinal Peptide (VIP)

VIP is a 28-aa neuropeptide and vasodilator that reduces inflammation, protects the CNS, supports gut-lung axis health, and modulates immune balance, especially in CIRS, fibrosis, and neuroinflammation.

- Reduce chronic inflammation and support immune balance

- Protect brain, gut, and lung tissue

Mechanism of Action

How this peptide works in the body

Receptor Binding:

Vasoactive Intestinal Peptide (VIP) binds to VPAC1 and VPAC2 receptors, activating adenylyl cyclase, which increases cyclic AMP (cAMP) levels. This cascade stimulates protein kinase A (PKA), leading to smooth muscle relaxation, vasodilation, and immune modulation. VPAC1 is primarily expressed in immune cells and epithelial tissues, while VPAC2 is prevalent in neurons and smooth muscle cells, allowing VIP to exert widespread anti-inflammatory and neuroprotective effects.

Cytokine Modulation:

VIP suppresses nuclear factor kappa B (NF-κB) activation, reducing transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ). Simultaneously, it upregulates anti-inflammatory cytokines (IL-10 and IL-4) via the STAT6 signaling pathway, shifting the immune response toward a regulatory and anti-inflammatory state.

Neuroprotection:

VIP preserves blood-brain barrier (BBB) integrity by enhancing tight junction protein expression (claudin-5, occludin, ZO-1), preventing neurotoxic infiltration. It also regulates beta-amyloid (Aβ) accumulation by modulating insulin-degrading enzyme (IDE) and neprilysin (NEP), reducing amyloid plaque formation in Alzheimer's disease models. Additionally, VIP enhances astrocyte and microglial function, mitigating oxidative stress and promoting neuronal survival via BDNF and NGF upregulation.

Gut-Brain Axis Regulation:

VIP enhances intestinal barrier integrity by increasing zonulin-1 expression, reducing gut permeability and bacterial translocation. This prevents lipopolysaccharide (LPS)-induced systemic inflammation and modulates the gut microbiome, favoring beneficial microbial populations. VIP also regulates vagal nerve signaling, influencing gut motility and reducing visceral hypersensitivity in conditions like IBS and IBD.