Fact Meets Function

This animal study tested orally administered Dihexa, an angiotensin IV analog that crosses the blood-brain barrier, in the APP/PS1 mouse model of Alzheimer’s-type pathology. Dihexa improved performance on spatial learning and memory testing, increased neuronal cell counts and synaptic protein expression, and reduced markers of neuroinflammation. The observed effects tracked with activation of the PI3K/AKT signaling pathway and were reversed when that pathway was blocked. This is animal model evidence and does not establish efficacy or safety in human populations.

This animal study evaluated whether mesenchymal stem cells, G-CSF, and/or Dihexa improve recovery of limb function after surgical repair of a transected sciatic nerve in rats. Sensory function returned to near normal across all groups by eight weeks, while motor function measured by walking print analysis improved significantly in groups receiving stem cells combined with either G-CSF or Dihexa. The design compares single and combination regimens in a peripheral nerve injury model. This is animal model evidence and does not establish efficacy or safety in human populations.

This preclinical study tested Dihexa, a chemically stable HGF mimetic, for its ability to protect sensory hair cells from damage caused by aminoglycoside antibiotics, using the larval zebrafish lateral line as a model for mammalian inner ear hair cells. A 1 micromolar concentration gave optimal protection against both neomycin and gentamicin, and protection was attenuated when an HGF antagonist was co-administered, supporting HGF pathway activation as the mechanism. Dihexa did not reduce antibiotic entry into the cells, indicating the effect is intracellular rather than a blocking action. This is animal model evidence and does not establish efficacy or safety in human populations.

This preclinical study (in vitro and animal model evidence) investigated how angiotensin IV-derived peptides, specifically dihexa, enhance cognitive function and synapse formation, finding that these effects depend on activation of the hepatocyte growth factor (HGF)/c-met signaling pathway. Researchers demonstrated that blocking the HGF/c-met system prevented the cognitive and synaptogenic benefits typically observed with these peptides in their experimental models. The findings suggest that the HGF/c-met pathway is a critical mechanism underlying the procognitive effects of angiotensin IV-derived peptides.

Researchers evaluated metabolically stabilized analogs of angiotensin IV in animal models to assess their potential effects on cognition and dementia-related outcomes. The study found that these modified compounds demonstrated procognitive properties in the tested animal models. This is animal model evidence and does not establish efficacy or safety in human populations.