Dihexa an oligopeptide derived from angiotensin IV, binds with high affinity to hepatocyte growth factor (HGF), acting as an allosteric modulator.
Dihexa directly enhances brain-derived neurotrophic factor (BDNF) signaling and levels. BDNF supports neuron survival, growth, and synaptic plasticity.
In cell assays, Dihexa is 7 orders of magnitude (10 million times) more potent than BDNF at inducing new synapse formation. Dihexa boosts BDNF production, mimicking its neurotrophic effects to promote synaptic connectivity in brain regions like the hippocampus. Preclinical studies in rat models of cognitive impairment show Dihexa improves memory and reverses amnesia by enhancing long-term potentiation (LTP), a BDNF-related process. This makes Dihexa a potential alternative or enhancer to BDNF therapies, which struggle with blood-brain barrier penetration and stability.
Dihexa is orally active, metabolically stable, and passes through the blood-brain barrier to exert its biological effects.
Anatomical structure of the blood–brain barrier (BBB). The wall of all brain capillaries is formed by a thin monolayer of specialized brain microvascular endothelial cells joined together by tight junctions, which act as a physical, transport and metabolic barrier. They are surrounded by a vascular basement membrane (BM), pericytes, a parenchymal BM and astrocyte endfeet, all of which directly or indirectly contribute to the barrier function of the BBB.
Dihexa involves the synthesis of new synapses, formally known as synaptogenesis; it has also been found to activate the receptors responsible for transmitting electric signals to neuron cells. These cognitive-enhancing properties have been demonstrated in animal studies to it can improve memory and learning abilities. Enhancing synaptic plasticity—synapses' power to strengthen connections and facilitate communication—may improve cognitive processes like memory formation, attention, and learning.
(1) A nerve impulse arrives. (2) This causes calcium ion channels to open, resulting in an influx of calcium ions in the terminal. (3) This causes synaptic vesicles to fuse with the terminal membrane, releasing neurotransmitter into the gap between neurons, known as the synaptic cleft. (4) The neurotransmitters bind to receptor sites on ion channels in the postsynaptic membrane, causing them to open. (5) Ions flow into the postsynaptic neuron, which generates an action potential when a threshold level is reached.
Another mechanism of action for Dihexa involves the activation of hepatocyte growth factor (HGF), which is implicated in the regulation of various brain functions, including neuroprotection. Neuroprotection refers to the preservation of neurons and the prevention of damage or degeneration in the brain. Animal studies have shown that it can promote the growth and survival of neurons, potentially enhancing their resilience and protecting them from damage. Supporting neuronal development can counteract the effects of neurodegenerative diseases and improve overall brain health.
In addition to its effects on neurons and cognitive function, it has been found to promote
angiogenesis, increasing VEGF, and facilitating the formation of new blood vessels.
The angiogenic cascade. During the process of angiogenesis, stable vessels (a) undergo a vascular permeability increase (this has been demonstrated only under certain conditions – see text), which allows extravasation of plasma proteins (b). Degradation of the ECM by MMPs relieves pericyte-EC contacts and liberates ECM-sequestered growth factors (c). ECs then proliferate and migrate to their final destination (d) and assemble as lumen-bearing cords (e). ECM, extracellular matrix; MMPs, matrix-metalloproteases; EC, endothelial cell.
Angiogenesis is a crucial process in developing and maintaining healthy tissues, including the brain. Encouraging the growth of new blood vessels may improve blood flow to the brain, providing oxygen and nutrients to support its functions. That could be particularly relevant in conditions where blood flow to the brain is compromised, such as stroke or certain neurodegenerative disorders.
Additionally, Dr. William Seeds has suggested that Dihexa peptide may possess some anti-inflammatory properties due to activation of the PI3K/AKT signaling pathway. The pathway also downregulates pro-inflammatory cytokines such as IL-1β and TNF-α while upregulating anti-inflammatory IL-10, attenuating neuroinflammation.
Dihexa potential application in different clinical research settings
Dihexa shows promise in treating Alzheimer's disease by rescuing cognitive impairment and ameliorating neuronal loss in preclinical models.
In Parkinson's disease, Dihexa may prevent disease progression and protect dopaminergic neurons through its HGF-mimetic effects.
The peptide could enhance cognitive function in age-related decline, improving memory and synaptogenesis in aging brains.
Dihexa has potential as an adjunct therapy for traumatic brain injury, modulating secondary injury mechanisms and promoting neuronal repair.
Dihexa combined with stem cells or G-CSF may accelerate limb functional recovery post-surgical repair for peripheral nerve injuries.
It holds clinical potential for protecting sensory hair cells from ototoxic damage, possibly aiding in hearing loss prevention.
Dihexa might alleviate symptoms of neuroinflammation-related disorders by upregulating anti-inflammatory cytokines like IL-10.
The compound could improve mental health in mood disorders by enhancing neurotrophic signaling and reducing apoptosis.
For post-COVID or chronic fatigue syndromes, Dihexa may address brain fog and cognitive fatigue through neuroprotection.
The possibility of using it to improve athletic performance has garnered increasing attention as a potential cognitive enhancer for sports.
Dihexa's ability to potentiate HGF/c-Met signaling suggests applications in broader neurodegenerative conditions like ALS or Huntington's disease. HED is for research purposes: starting with 10mg, weekly increase to 40mg.
Dihexa is studied as a research compound in experimental models exploring neurotrophic signaling and synaptic plasticity.
→ Dihexa (20 mg, research-grade)
For a broader comparison of neuropeptide research molecules, including Dihexa, Semax, and Selank, see our comparative overview. - Read More