Animal only
This animal study investigated whether Growth Hormone-Releasing Peptide-6 (GHRP-6), a GH secretagogue hexapeptide, could reduce cardiac damage following myocardial infarction. Using a permanent left coronary artery ligation model in rats (a non-reperfusion model), researchers divided animals into three groups: sham-operated controls, infarcted rats treated with saline, and infarcted rats treated with GHRP-6. Treatment began post-surgery and continued for seven days. Outcomes were assessed via echocardiography and histology on day seven. A separate cohort of twelve healthy rats was used for mitochondrial proteomic analysis six hours after compound administration. The study found that, compared to the saline-treated infarcted group, GHRP-6-treated rats showed reduced myocardial tissue loss, less interstitial fibrosis and scarring, and improved left ventricular function. Proteomic data suggested that potential mechanisms may include upregulation of fatty acid beta-oxidation, apoptosis-prevention pathways, antioxidant defenses, and mitochondrial metabolic reprogramming. Key limitations include the exclusive use of an animal model, a short seven-day observation window, a small sample size, and the mechanistic proteomic findings being derived from healthy rather than infarcted animals. No human data were generated.
Pharmaceuticals (Basel, Switzerland) · Mar 2026DOI ↗ Animal only
This mouse study investigated whether Growth Hormone Releasing Peptide-6 (GHRP-6) could protect against acute lung injury (ALI) and its progression to pulmonary fibrosis. Researchers used two established animal models: intratracheal lipopolysaccharide (LPS) instillation and a combined zymosan (ZYM) plus platelet-activating factor (PAF) injection. Both acute (24-hour to 15-day) and chronic (28-day) scenarios were examined. In the acute setting, GHRP-6 treatment was associated with reduced neutrophilic alveolitis, improved lung compliance, better alveolar-capillary permeability, and lower serum interleukin-1 beta levels compared to saline controls. In the chronic setting, GHRP-6-treated animals showed better preservation of lung parenchymal architecture and notably less collagen accumulation, suggesting reduced progression to fibrosis. The authors describe this as the first assessment of GHRP-6's protective potential in lung injury models. Key limitations include exclusive use of mouse models with no human data, multiple treatment variables across scenarios, and the lack of mechanistic depth regarding GHRP-6's specific molecular targets in lung tissue. The authors conclude that findings warrant future investigation into GHRP-6's pneumoprotective effects.
International immunopharmacology · Jan 2026DOI ↗ Animal only
This animal study investigated whether orally administered salmon acylated ghrelin (sAG) could stimulate food intake in common carp (Cyprinus carpio) and sought to identify the local mechanism behind any such effect. Carp were fed experimental diets containing a range of sAG concentrations in single-shot feeding trials, and additional voluntary feed intake was measured afterward. The study found that diets containing sAG at or above a certain threshold produced a significant, dose-dependent increase in feed intake that plateaued at higher concentrations. Notably, plasma ghrelin levels did not rise following oral administration, as confirmed by two separate radioimmunoassay methods, suggesting that sAG was not absorbed into the bloodstream. To probe the mechanism, researchers used a ghrelin receptor antagonist ([D-Lys3]-GHRP-6) and capsaicin — both abolished the orexigenic effect — pointing to a local signaling pathway involving growth hormone secretagogue receptors and peripheral sensory (likely vagal afferent) neurons. The authors propose this represents a non-circulatory gut-brain axis mechanism in fish. Limitations include that results are limited to a single fish species under controlled laboratory conditions, and translation to other vertebrates or aquaculture settings requires further research.
Animal only
This study investigated the central effects of Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) on food intake in broiler chickens, and explored its potential interactions with the ghrelin and cannabinoid systems. Four separate experiments were conducted, each with four groups of neonatal broiler chickens receiving intracerebroventricular (ICV) injections. Experiment 1 tested LEAP-2 alone at three doses; Experiments 2–4 tested LEAP-2 in combination with a ghrelin receptor antagonist (D-Lys-3)-GHRP-6, a CB1 receptor antagonist (SR141716A), and a CB2 receptor antagonist (AM630), respectively. Food consumption was measured at 30, 60, and 120 minutes post-injection. The study reported that ICV LEAP-2 at the two higher doses significantly reduced cumulative food intake compared to saline controls. The interaction experiments suggested that LEAP-2's appetite-suppressing effects may involve both CB1 and CB2 cannabinoid receptors as well as the ghrelin receptor system. Key limitations include the exclusive use of an avian (broiler chicken) model, small experimental group sizes, a single-species focus, and the lack of direct mechanistic or molecular data. Findings cannot be directly extrapolated to humans or mammals without further research.
Poultry science · Dec 2025DOI ↗ Animal only
This study investigated whether a self-assembling Growth Hormone-Releasing Peptide-6 (GHRP-6) peptide hydrogel could improve outcomes in acute kidney injury (AKI) by targeting metabolic reprogramming in renal tubular epithelial cells (TECs). Using a mouse model of AKI (likely ischemia-reperfusion injury), the researchers administered the GHRP-6 hydrogel and performed metabolomic sequencing analysis to characterize changes in cellular metabolism. The study found that treatment was associated with elevated levels of spermidine, L-glutamine, and acetyl-CoA — metabolites linked to amino acid and fatty acid metabolism — suggesting a favorable metabolic shift in TECs. Further mechanistic experiments indicated that the GHRP-6 hydrogel promoted TEC survival under ischemic conditions by activating the mTOR-P70 signaling pathway. The authors conclude that GHRP-6 hydrogel may protect TECs and reduce the risk of post-AKI fibrosis through metabolic reprogramming. Key limitations include that findings are restricted to a mouse model with no human data, the sample sizes and controls are not detailed in the abstract, and translation to clinical settings remains undemonstrated. The novel hydrogel formulation adds a materials-science dimension but also introduces additional variables requiring further study.
Journal of nanobiotechnology · Dec 2025DOI ↗ Limited · human
This experimental study investigated the potential of Growth Hormone Releasing Protein-6 (GHRP-6), a ghrelin hormone agonist, to improve in vitro maturation (IVM) of human oocytes. Researchers collected 240 human germinal vesicle (GV) oocytes and cultured them in varying concentrations of GHRP-6, comparing outcomes against a blastocyst single-step culture medium (control) and human tubal fluid (HTF) 10% (sham). Maturation rates were tracked over two days. A subset of 164 GV oocytes was then used to assess gene expression of CENP-E (associated with meiotic progression) and LINGO2 (a membrane protein gene) via real-time PCR after 24 hours of culture. The study found that a specific concentration of GHRP-6 produced the highest maturation rates on both day one and day two, outperforming both comparison media. However, real-time PCR analysis revealed that GHRP-6 did not significantly elevate expression of either CENP-E or LINGO2 in metaphase II oocytes, suggesting nuclear maturation was promoted without a corresponding improvement in cytoplasmic maturation markers. Key limitations include the absence of downstream developmental outcomes (e.g., fertilization or embryo quality data), a relatively small oocyte sample, and the lack of blinded assessment or patient-level randomization.
International journal of fertility & sterility · Sep 2025DOI ↗ Animal only
This study investigated whether dietary supplementation with GHRP-6, a synthetic ghrelin analog peptide, could modulate endocrine and immune responses in gilthead seabream (Sparus aurata), a commercially important aquaculture species. Fish were fed diets containing GHRP-6 for 97 days and then challenged with Incomplete Freund's Adjuvant (IFA), an immune stimulant, via intraperitoneal injection. Samples were collected 72 hours post-injection. The study found that GHRP-6-fed fish maintained more stable plasma levels of lactate, triglycerides, and cortisol following IFA challenge compared to control fish, suggesting reduced metabolic stress. Circulating immunoglobulin levels were significantly elevated in the GHRP-6/IFA group, indicating enhanced humoral immunity. Transcriptomic analysis showed the anterior intestine was the most responsive tissue, with upregulation of immune-related genes including il10, il15, il34, and mx1. Spleen tissue showed increased expression of il8, il10, and ighm, suggesting a balanced inflammatory response. No histological damage was observed in the intestine or spleen. Limitations include the exclusive use of a single fish species, no mammalian or human data, a single GHRP-6 dietary concentration tested, and the authors themselves characterize results as "preliminary."
Animal only
This study investigated whether the synthetic hexapeptide Growth Hormone-Releasing Peptide-6 (GHRP-6), a ghrelin analog with known growth-promoting and immunomodulatory properties in fish, could protect against Nervous Necrosis Virus (NNV) — a pathogen that damages the central nervous system of many commercially farmed fish species. The researchers used two complementary approaches. In vitro, E11 fish cell lines were treated with GHRP-6 before and/or during NNV infection; treated cells showed higher survival rates, reduced viral genome replication, and lower production of infective viral particles compared to untreated controls. In vivo, European seabass (Dicentrarchus labrax) were given intraperitoneal injections of GHRP-6, which led to significant upregulation of immune-related genes — including TNF-α, RTP3, and IgM — in the head kidney and intestine. NNV replication in the brain was also lower in GHRP-6-treated fish than in controls, and the brain's antiviral immune response was modulated. The authors conclude that GHRP-6 shows potential as an antiviral agent for aquaculture disease prevention. Key limitations include that all experiments were conducted in fish (not humans) and the in vivo work lacked a full challenge trial design.
Aquaculture international · Jun 2025
Animal only
This mouse study investigated whether intranasal administration of ghrelin, GHRP-6, or MK-0677 could activate the brain's ghrelin signaling system. Researchers first screened compounds and doses by measuring food intake after intranasal application. Of the three compounds tested, only GHRP-6 at a specific dose increased food intake without adverse effects and was selected for detailed analysis. Investigators then examined meal patterns, neuronal activation in the arcuate nucleus of the hypothalamus using Fos mapping, and neurochemical identity of activated neurons using RNAscope in situ hybridization. They also measured serum growth hormone (GH) levels. The study found that intranasal GHRP-6 increased food intake by raising both meal frequency and meal size. Fos expression in the arcuate nucleus was significantly elevated compared to saline controls, and activated neurons showed co-expression with GHSR, AgRP, and GHRH mRNA markers, implicating circuits involved in feeding and GH regulation. Serum GH levels were also elevated following intranasal GHRP-6. Limitations include exclusive use of a mouse model, a single species and sex are not specified, and the absence of human or pharmacokinetic data, meaning translation to clinical settings remains uncertain.
Endocrinology · Feb 2025DOI ↗ Review
This narrative review examines the potential adjunctive role of growth hormone secretagogues (GHS) in managing body composition changes associated with male hypogonadism and metabolic syndrome. The authors acknowledge that while testosterone replacement therapy remains the standard of care for hypogonadism, its body composition benefits are inconsistent across patient populations. The review surveys existing literature on five GHS compounds — sermorelin, GHRP-2, GHRP-6, ibutamoren (MK-677), and ipamorelin — noting that all stimulate growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion and may improve body composition metrics such as reducing fat mass and attenuating muscle atrophy. The authors also explore their potential utility in eugonadal males with metabolic syndrome or subclinical hypogonadism. A major limitation explicitly acknowledged by the authors is the scarcity of robust clinical trial data evaluating these compounds specifically in hypogonadal men. The review concludes that while GHS show theoretical and preliminary promise as complementary agents, the current evidence base is insufficient to draw firm clinical conclusions, and the authors call for future controlled investigations. No new primary data are presented.
Translational andrology and urology · Mar 2020DOI ↗ Limited · human
This study developed and validated an analytical method for detecting a broad panel of 18 performance-enhancing peptides (molecular weight <2 kDa) in human urine, as defined by the World Anti-Doping Agency (WADA) prohibited list. The method uses direct urine injection—bypassing complex sample preparation—coupled with liquid chromatography and ion mobility time-of-flight mass spectrometry (IM-TOFMS). The researchers reported limits of detection (LOD) ranging from 50 to 500 pg/mL, well below WADA's minimum required performance level of 2 ng/mL. The method demonstrated acceptable precision (imprecision <20%) and linearity across a 0–10 ng/mL working range. Stability testing identified –20°C as the appropriate storage temperature for urine samples. As a proof-of-concept, the method was applied to real elimination study urine samples from individuals who had administered GHRP-2, GHRP-6, or LHRH, successfully detecting these compounds. Key limitations include the small number of human subjects used in the elimination studies, which were primarily intended to demonstrate analytical feasibility rather than investigate pharmacokinetics or clinical effects. The study is a methodological/analytical validation paper focused on anti-doping screening, not a clinical or therapeutic investigation.
Journal of separation science · Dec 2015DOI ↗ Animal only
This study compared the pharmacokinetics of five peptidyl growth hormone secretagogues — ipamorelin (NNC 26-0161), NNC 26-0194, NNC 26-0235, GHRP-2, and GHRP-6 — in male rats using multiple routes of administration, with a particular focus on nasal delivery. Following intravenous bolus injection, all peptides showed biexponential plasma concentration decline. Ipamorelin stood out with a systemic plasma clearance approximately five times lower than GHRP-6. Excretion routes differed: ipamorelin was primarily cleared via urine, while GHRP-6 and the two NNC peptides were predominantly excreted in bile. Metabolic stability was moderate for ipamorelin and the NNC peptides, with 60–80% of administered doses recoverable as intact peptide from bile and urine combined. Intranasal bioavailability of ipamorelin was estimated at approximately 20%, while NNC 26-0235, NNC 26-0194, and GHRP-2 achieved approximately 50% nasal bioavailability. The authors concluded that nasal delivery appears to be a promising route for this peptide class. Key limitations include exclusive use of animal subjects (male rats), meaning findings may not directly translate to humans, and the study did not assess pharmacodynamic or safety endpoints.
Xenobiotica; the fate of foreign compounds in biological systems · Nov 1998DOI ↗