GHRP-6

Abstract

Acute lung injury/acute respiratory distress syndrome is a complex, characterized by acute onset, alveolar damage, and progressive hypoxemia. The subsequent proliferative phase drives to pulmonary fibrosis. Lipopolysaccharide (LPS) and zymosan (ZYM) induced lung injury are commonly used biomodels that recapitulate multiple pathogenic hallmarks. We examined the ability of growth hormone releasing peptide 6 (GHRP-6) to attenuate the pulmonary damages associated with intratracheal instillation of LPS or ZYM combined injection with platelet activating factor (PAF) in mice. For the acute scenario, mice received LPS challenge and 6 h later, assigned to normal saline (Control) or to a single administration of each GHRP-6 dose and evolved for 24 h; or mice received four ZYM tracheal instillations and 6 h after, one PAF injection assigned to normal saline (Control) or to five administrations of each GHRP-6 dose and evolved for 15 days. For the chronic scenario, mice were terminated 28 days after receiving a single LPS instillation and seven subsequent daily administrations of GHRP-6; or mice were terminated 28 days after receiving five GHRP-6 therapeutic interventions after four ZYM tracheal instillations and one PAF injection. The acute scenario, GHRP-6 reduced neutrophilic alveolitis, attenuated lung compliance failure, contributed to improve alveolar-capillary permeability, and reduced interleukin-1 beta serum levels. The chronic scenario, GHRP-6 preserved lung parenchymal integrity accounted for meager collagen accumulation. This is the first assessment on the potential protective of GHRP-6 in model of lung damages. This study therefore paves the way for future research on the potential pneumoprotective effects of GHRP-6.

Abstract

This study clarified the local mechanism of action and assessed the aquaculture potential of orally administered salmon acylated ghrelin (sAG) on feed intake in common carp (Cyprinus carpio). Experimental diets containing sAG (ranging from 0.001 to 13.04 µg/g) were prepared and fed to carp at 2.0 % of body weight (BW) in single-shot trials. Fish receiving diets of 0.64 µg/g (1.3 µg/100 g BW) or higher exhibited a significant, dose-dependent increase in additional feed intake, plateauing at 1.20 µg/g (2.4 µg/100 g BW). Despite this behavioral effect, plasma ghrelin levels remained unchanged, as measured by both N-terminal and salmon-specific C-terminal radioimmunoassays, confirming that sAG was not systemically absorbed. The orexigenic effect was abolished by pretreatment with the ghrelin receptor antagonist [D-Lys3]-GHRP-6 or with capsaicin, demonstrating local sAG action via growth hormone secretagogue receptor signaling and peripheral sensory neurons (likely vagal afferents). These findings provide the first evidence that fish ghrelin exerts biological activity via a non-circulatory neuroendocrine pathway. This advances our understanding of the vertebrate gut-brain axis and highlights the potential of harnessing locally acting peptides for physiological modulation in aquatic species.

Abstract

Liver-expressed antimicrobial peptide 2 (LEAP-2), initially identified as an antimicrobial peptide which endocannabinoid and ghrelin action may occur via changes in Leap2 expression. This study aimed to determine effect of ICV injection of LEAP2and its interaction with cannabinoid and ghrelin systems on food intake in broiler chickens. In the present study 4 experiments were conducted, each containing 4 experimental groups. In experiment 1, chicken injected with group 1 ICV injection of saline, group 2 with LEAP2 (0.75 nmol), group 3 with LEAP2 (1.5 nmol) and group 4 with LEAP2 (3 nmol). In experiment 2, chicken received ICV injections as group 1: saline, group 2: (D-Lys-3)-GHRP-6 (0.5 nmol), group 3: LEAP2 (3 nmol) and group 4 with co injection of the (D-Lys-3)-GHRP-6 + LEAP2. In experiment 3 chiken received ICV inejctions as: group 1: saline, group 2: SR141716A (6.25 µg), group 3: LEAP2 (3 nmol) and group 4 with co injection of the SR141716A + LEAP2. In experiment 4 chiken received ICV inejctions as: group 1: saline, group 2: AM630 (1.25 µg), group 3: LEAP2 (3 nmol) and group 4 with co injection of the AM630 + LEAP2. Immediately following the infusions, the broilers were returned to their respective boxes, where they were provided with pre-weighed meal and fresh water ad libitum. The cumulative meal consumption was subsequently measured at intervals of 30, 60, and 120 min post-administration. According to the results, ICV injection of the LEAP2 (1.5 and 3 nmol) significantly decreased food intake (P<0.05). Co-injection of the (D-Lys-3)-GHRP-6 + LEAP2 significantly decreased LEAP2-induced hypophagia (P<0.05). Co-injection of the (D-Lys-3)-GHRP-6 + LEAP2 significantly increased hypophagic effect of the LEAP2 (P<0.05). Co-injection of the SR141716A + LEAP2 significantly amplified LEAP2-induced hypophagia compared to control group (P<0.05). Co-injection of the AM630 + LEAP2 significantly amplified LEAP2-induced hypophagia compared to control group (P<0.05). These results suggested that LEAP2-induced hypophagia mediates via ghrelin and CB1 and CB2 receptors in neonatal chicken.

Abstract

Renal tubular epithelial cells (TECs), which are highly susceptible to injury during acute kidney injury (AKI), have notable regenerative effects on renal recovery after AKI. AKI-driven metabolic reprogramming of TECs plays a critical role in determining whether kidneys recover functionally or develop fibrosis. Targeting the metabolism of TECs offers valuable insights into AKI treatment. Growth hormone-releasing hormone (GHRH) and its analog GHRH peptide (GHRP) play beneficial roles in the field of regenerative medicine. Here, we designed a self-assembling GHRP-6 peptide hydrogel, and we hypothesized that this hydrogel could reprogram the metabolism of TECs, further enhancing recovery from AKI. Metabolomic sequencing analysis revealed that spermidine, L-glutamine, and acetyl-CoA, which are involved in amino acid and fatty acid metabolism, were highly enriched in a mouse model of AKI treated with the GHRP-6 hydrogel. Further study revealed that GHRP-6 hydrogel treatment enhanced the survival of TECs in the ischemic microenvironment by activating the mTOR-P70 pathway. In conclusion, GHRP-6 hydrogel treatment has beneficial therapeutic effects on AKI through the targeting of metabolic reprogramming, which offers a novel therapeutic strategy to protect TECs in AKI treatment.

Abstract

Isotryptophan (Itr) is the rare 2-indoyl counterpart of the essential amino acid tryptophan. Considering the potential to explore novel side chain χ-space in a residue prone to adopt backbone turn conformers, azaItr has been effectively synthesized and employed in Pictet-Spengler and peptide chemistry. β-Turn geometry was characterized in model peptides of the Ala-azaItr-d-Phe triad by X-ray and NMR analyses. Moreover, azaItr analogs of growth hormone-releasing peptide 6 (GHRP-6) demonstrated a promising cluster of differentiation-36 receptor (CD36) binding affinity and modulatory effect on the inflammatory response induced by the activated complex composed of the latter coreceptor in the Toll-like receptor-2/6 heterodimer.

Abstract

The aquaculture industry has experienced considerable growth in recent decades, stimulating research into sustainable and functional feed formulations, mainly related to using high-quality, safe, and environmentally friendly feed ingredients. The employment of immunomodulatory additives is a promising strategy to enhance fish health and performance. In this study, the effects of the ghrelin analog GHRP-6 peptide included in the diet (500 µg/kg of feed) on the endocrine and immune responses of Sparus aurata following Incomplete Freund's adjuvant (IFA) treatment were assessed. After 97 days, fish were intraperitoneally injected with 100 µL of saline solution or IFA/100 g fish and sampled 72 h post-injection. Our results indicated that fish fed GHRP-6 maintained stable plasma levels of lactate, triglycerides, and cortisol after IFA treatment, in contrast to control-fed fish, which showed significant metabolic stress. Circulating immunoglobulin levels enhanced significantly in the GHRP-6/IFA group, suggesting a stimulated humoral immune response. Transcriptomics analysis revealed that the anterior intestine was the most responsive tissue, with upregulation of il10, il15, il34, and mx1, indicating mucosal immune activation. In the spleen, GHRP-6-fed fish increased il8, il10, and ighm expression, highlighting a balanced pro- and anti-inflammatory response and support for adaptive immunity. Multivariate analysis confirmed that dietary GHRP-6 modulates immune gene expression in a tissue- and stimulus-specific manner, without inducing histological alterations in the intestine or spleen. Taken together, these preliminary results indicate that this peptide is a viable and safe dietary supplement to improve immune resilience and increase the production efficiency of S. aurata and suggest a protective effect on the fish's immune system in this species.

Abstract

Major depressive disorder (MDD) is often treatment resistant, particularly in addressing anhedonia and cognitive deficits. Novel pharmacological strategies are needed. While butyrylcholinesterase, ghrelin, and dopamine (DA) have been well studied in the context of stress and MDD, their interaction remains unclear.

Abstract

Guanxin II, proposed by Chen Keji (National master of traditional Chinese medicine), possesses neuroprotective effect. Interestingly, its simplified prescription Danshen-Chuanxiong-Honghua (DCH) can also clinically ameliorate cerebral impairment and improve spatial cognitive deficits, similar to the function of original formula.

Abstract

Cystic echinococcosis (CE) is a parasitic disease caused by the larval stage of Echinococcus granulosus, and the immunosuppressive microenvironment exacerbates disease progression. Ghrelin, a peptide hormone, plays a role in modulating immune inflammation and may influence the progression of E. granulosus infection through its receptor, GHSR (growth hormone secretagogue receptor). However, whether GHSR downregulation can inhibit E. granulosus infection remains unclear. In this study, we extracted liver tissues from E. granulosus-infected mice and those treated with the GHSR antagonist [D-Lys3]-GHRP-6. Proteomic analysis revealed 341 differentially expressed proteins, of which 185 were upregulated and 156 were downregulated. Metabolomic sequencing revealed 101 differentially expressed metabolites, including 62 upregulated and 39 downregulated metabolites. KEGG pathway enrichment analysis of both proteomic and metabolomic data revealed seven key signalling pathways, 11 key proteins, and 26 key metabolites that interact through metabolic and organic system networks. Next, we examined the disease progression of E. granulosus infection in GHSR-knockout mice. Compared with the E. granulosus (Eg) group, the GHSR-KO group presented a significant reduction in the number of liver infection foci. The serum and liver ghrelin levels were significantly greater in the E. granulosus group than in the control group, along with increased secretion of proinflammatory cytokines (IL-2 and IFN-γ) and decreased secretion of anti-inflammatory cytokines (IL-4 and IL-10). In contrast, the GHSR-KO group presented significantly lower ghrelin levels in both the serum and liver, with reduced proinflammatory cytokine secretion and increased anti-inflammatory cytokine secretion, similar to those of the control group. Furthermore, ghrelin and inflammation-related factors, including MyD88, NF-κB p65, iNOS, and Arg-1, exhibited coordinated expression changes in liver lesions and surrounding areas. These findings suggest that GHSR gene knockout can ameliorate the progression of liver E. granulosus infection and associated liver inflammation.

Abstract

CIGB-500 is a product whose active pharmaceutical ingredient is GHRP-6, (Growth Hormone Releasing Peptide-6), a synthetic peptide that allows the rescue of cardiac mass affected during Acute Myocardial Infarction. The objective of the study was to determine the toxicity profile of CIGB-500 in dogs. As general methodology, CIGB-500 was administered daily to dogs by intravenous route for 28 consecutive days. All animals were allocated to four groups: Control, Low-Dose (300 μg/kg/day), Mid dose (1000 μg/kg/day) and High-Dose (2000 μg/μg/day). Hypersalivation, hypoactivity, reduced heart rate, changes in respiration, pale gums and erythema of the head region were observed in some animals administered at 1000 and 2000 μg/kg/day. These clinical signs were transient, and were therefore considered non-adverse. Treatment with CIGB-500 did not result in any adverse macroscopic or microscopic changes. A decrease in heart rate value was noted following CIGB-500 treatment at all dose levels an at the end of recovery period, the heart rate effects at 2000 μg/kg/day were comparable to controls. In conclusion, the daily administration of CIGB-500 at doses up to 2000 μg/kg/day was well-tolerated, findings noted were transient, minor, non-adverse and reversible, and the no observable adverse effect level (NOAEL) was considered to be 2000 μg/kg/day.