Animal only
This animal study investigated the neuroprotective effects of hexarelin, a growth hormone secretagogue receptor type 1a (GHS-R1a) agonist, on retinal ganglion cell (RGC) survival following optic nerve transection (ONT) in golden hamsters. Researchers administered hexarelin at varying doses either once or twice daily for five days post-ONT and quantified RGC survival at seven days using Tuj1 immunostaining on retinal whole mounts. Single daily doses (25, 50, and 100 µg/kg) produced a dose-dependent increase in RGC survival compared to saline controls (62.4%, 68.5%, and 74.6% vs. 51.2%, respectively). Twice-daily dosing yielded further improvements, with the highest tested regimen (150 µg/kg twice daily) associated with a survival rate exceeding baseline (109.2% vs. 72.9% for twice-daily saline). The study suggests hexarelin may exert anti-apoptotic neuroprotective effects in the retina, attributed to its GHS-R1a agonism. Key limitations include the use of a single animal species (golden hamster), absence of mechanistic pathway data, and no translation to human subjects or disease models such as glaucoma.
Indian journal of pharmacology · Mar 2026DOI ↗ Animal only
This study investigated whether hexarelin — a synthetic peptide ligand targeting the CD36 receptor — could reduce the hyper-inflammatory response associated with severe SARS-CoV-2 infection. Using the K18-hACE2 transgenic mouse model, which expresses the human ACE2 receptor and is widely used to study COVID-19 pathology, the researchers examined how SARS-CoV-2 infection drives alveolar macrophages toward a pro-inflammatory phenotype and whether CD36 modulation could interrupt this process. The study found that CD36 signaling appears to play a regulatory role in macrophage-driven cytokine overproduction — the so-called "cytokine storm" — and that hexarelin treatment showed potential for blunting this response, thereby potentially limiting progression to acute respiratory distress syndrome (ARDS). The study is limited by its reliance on an animal model, meaning results may not translate directly to human patients. The transgenic mouse system, while a useful proxy for human COVID-19, does not fully recapitulate human immunological complexity. No clinical data in humans were presented. The authors acknowledge that ARDS from SARS-CoV-2 remains an unmet therapeutic need and position hexarelin as a candidate for further investigation.
Frontiers in pharmacology · Feb 2024DOI ↗ Animal only
This study investigated whether the growth hormone-releasing peptide Hexarelin could protect against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and explored its molecular mechanisms. Using a rat I/R model, animals were pretreated with Hexarelin for seven days before injury induction. Researchers assessed kidney function (serum creatinine), histology (tubular necrosis and dilation), and apoptosis markers. In vitro, a hypoxia/reoxygenation (H/R) model in human kidney tubular (HK-2) cells was used to complement findings. The study reports that Hexarelin pretreatment reduced pathological kidney changes, improved renal function, and suppressed apoptosis, as evidenced by downregulation of pro-apoptotic proteins (Caspase-3, Bax, Bad) and upregulation of anti-apoptotic Bcl-2. Gene Set Enrichment Analysis (GSEA) highlighted the apoptosis pathway's role in I/R-AKI. Molecular docking suggested Hexarelin binds MDM2, a negative regulator of p53, and both MDM2 and p53 expression were suppressed by Hexarelin in vivo and in vitro. Key limitations include exclusive use of animal and cell models with no human data, a relatively narrow mechanistic focus, and reliance on computational docking without direct protein-interaction validation.
European journal of medical research · Sep 2023DOI ↗ Animal only
This study investigated whether hexarelin, a synthetic growth hormone-releasing peptide, could reduce the development of abdominal aortic aneurysm (AAA) using an elastase-induced mouse model. Mice received hexarelin injections twice daily, and outcomes were assessed via echocardiography, in situ imaging, histology, and molecular analyses. The study found that hexarelin-treated mice showed reduced infrarenal aortic diameter and improved elastin integrity compared to untreated controls. At the cellular level, hexarelin appeared to preserve smooth muscle cell (SMC) contractile phenotype, evidenced by increased α-SMA expression and decreased MMP2. Additionally, hexarelin was associated with reduced inflammatory cell infiltration, suppression of NLRP3 inflammasome activation, lower IL-18 production, and inhibition of the NF-κB signaling pathway. The authors concluded that hexarelin attenuates AAA development by targeting SMC phenotype switching and NF-κB-mediated inflammation. Key limitations include the exclusive use of an animal model, meaning findings have not been validated in humans, and the mechanistic conclusions are based on a single preclinical model that may not fully replicate human AAA pathophysiology.
Microvascular research · Nov 2021DOI ↗