VIP - VASOACTIVE INTESTINAL PEPTIDE - 6 mg

VIP (Vasoactive Intestinal Peptide) is a 28-amino acid neuropeptide belonging to the secretin-glucagon peptide family, which also includes glucagon, secretin, PACAP, GHRH, and related regulatory hormones. Originally isolated from the intestine, VIP is now recognized as a key molecule with a wide range of biological effects in both the central and peripheral nervous systems.

This molecule is synthesized as preproVIP, containing the VIP sequence and an accessory peptide (PHM in humans, PHI in other species). VIP is expressed in numerous areas of the body: brain, gastrointestinal tract, pancreas, lungs, heart, thyroid, adrenal glands, and thymus. It is produced not only by neurons, but also by endocrine and immune cells, underscoring its vital role at the interface of the nervous and immune systems.

Structurally, VIP features two beta-turns at the N-terminal and two central helices that provide functional flexibility. Binding of VIP to the GPCRs VPAC1 and VPAC2 enables precise modulation of various biological activities across multiple tissues.

Its main functions include:

• Neuroprotective and neurotrophic role: VIP is crucial for central nervous system health. It supports blood-brain barrier integrity, reduces neuroinflammation, and protects against oxidative stress. It has been shown to reduce beta-amyloid accumulation in Alzheimer’s models, counteract neurodegeneration in Parkinson’s disease, and promote myelination in the developing brain. In Parkinson’s disease, VIP shifts the immune balance from pro-inflammatory Th1 to anti-inflammatory Th2 responses. VIP’s protective CNS effects are mediated by VPAC1 and VPAC2 receptors, which stimulate the secretion of neurotrophic factors such as ADNP and BDNF, essential for synapse and astrocyte support.
• Circadian rhythm regulation: VIP helps synchronize circadian rhythms via its action on neurons in the suprachiasmatic nucleus of the hypothalamus.
• Gastrointestinal regulation: VIP acts as a modulator of digestive tract activity, promoting smooth muscle relaxation, water secretion, and nutrient absorption. It maintains autonomic balance within the gut.
• Gut barrier protection: In inflammatory bowel diseases such as Crohn’s and ulcerative colitis, VIP strengthens epithelial barrier integrity and reduces Th1-mediated inflammation, supporting IL-10 production by regulatory T cells.
• Antifibrotic and anti-inflammatory actions: VIP has been shown to reduce fibrosis in organs such as the heart, lungs, and intestines by suppressing NFAT and limiting smooth muscle cell proliferation. This highlights its promise for managing cardiac and pulmonary fibrosis, including in COPD and pulmonary hypertension.
• Cardiovascular system: VIP acts as a vasodilator, enhancing coronary flow and modulating vascular tone. It promotes nitric oxide production, lowers mean arterial pressure, and exerts positive inotropic effects on the heart. Preclinical studies show it reduces expression of genes involved in cardiac remodeling, suggesting a role in preventing cardiac fibrosis.
• Immune function: VIP regulates both innate and adaptive immunity. In the innate arm, it suppresses pro-inflammatory cytokines like TNF-α and IL-6, and modulates dendritic cells, macrophages, and neutrophils. In adaptive immunity, it supports immune tolerance by promoting regulatory T cells and shifting toward Th2 responses, thus reducing autoimmunity and chronic inflammation.
• Organ transplantation: VIP may serve as a targeted immunomodulator in transplantation by selectively inhibiting dendritic cells responsible for graft rejection, fostering tolerance without the side effects of traditional immunosuppressants.
• Respiratory diseases and COVID-19: In addition to its known bronchodilatory effects, VIP (in the synthetic form Aviptadil) has shown clinical promise in severe COVID-19 cases by enhancing oxygen saturation, improving lung function, and protecting alveolar cells. Its impact on pulmonary vasculature also makes it a candidate for treating pulmonary hypertension and preventing lung fibrosis.
• Systemic fibrosis: VIP has demonstrated global antifibrotic effects, potentially beneficial in liver, cardiac, intestinal, and pulmonary fibrosis. It appears to reduce angiotensinogen and AT1a receptor expression, similar to the effects of ACE inhibitors.
• Neurodegenerative diseases: In Alzheimer’s and Parkinson’s models, VIP reduces oxidative stress and inflammation, while promoting secretion of neurotrophic factors such as BDNF and ADNP, which are essential for synaptic and astrocyte survival.
• Mold-related illness and CIRS: VIP has been explored for its role in chronic inflammatory response syndrome (CIRS) due to mold exposure. Shoemaker’s research suggests VIP normalizes abnormal gene activation patterns associated with chronic environmental inflammation.
• Lacrimal Secretion Regulator: Regarding its effect on lacrimal gland function, several studies suggest that VIP may play a regulatory role in tear secretion, due to its neurotrophic, vasodilatory, and anti-inflammatory activity at the level of the lacrimal glands. Specifically, VIP has been shown to: Stimulate fluid secretion in the ducts of the lacrimal glands through activation of the cAMP-CFTR signaling pathway; Enhance protein secretion from lacrimal acinar cells, contributing to the maintenance of tear film composition; Modulate the activity of the parasympathetic nervous system; Exert protective effects in cases of inflammation or dry eye conditions.

Specifically, VIP has been shown to:

• Stimulate fluid secretion in lacrimal gland ducts via the cAMP-CFTR signaling pathway;
• Increase protein secretion from lacrimal acinar cells, maintaining tear film composition;
• Modulate parasympathetic nervous system activity;
• Provide protective effects against inflammation or dry eye conditions.