Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds

Abstract

In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6) proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ) were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit's ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit's model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms

“…GHRP-6 has proved to prevent and attenuate cardiac cell death and LV failure in a variety of experimental scenarios ( Lucchesi, 2004 ; Xu et al, 2005 ; Berlanga-Acosta et al, 2016 ; Berlanga-Acosta et al, 2017 ). Furthermore, we have also identified GHRP-6 anti-fibrotic properties which may contribute to mitigate the systemic complications of Dox administration ( Berlanga-Acosta et al, 2012 ; Mendoza et al, 2016 ; Fernandez-Mayola et al, 2018 ). Beyond its ability to enhance the survival of a diversity of cells before an otherwise lethal stress, GHRP-6 and other mimetic ligands to the GHSR1a and CD36 receptors, play an agonistic effect on the GH/IGF-1 axis promoting a systemic anabolic response, and counterbalancing catabolism and sarcopenia ( Giorgioni et al, 2022 ).…”

Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

“…Our group has contributed to validate the potential antifibrotic abilities of GHRP-6 in animal models of liver cirrhosis 38 and hypertrophic scars, 39 in which via a peroxisomal proliferator-activated receptor gamma (PPARγ)-driven cascade, GHRP-6 intervention reduced TGF-β1 and connective tissue growth factor (CTGF) expression, which translated in a dramatic reduction in the accumulation of collagen and other extracellular matrix (ECM) proteins.…”

Growth hormone‐releasing peptide 6 prevents cutaneous hypertrophic scarring: early mechanistic data from a proteome study

“…Previous findings from our group demonstrate GHRP6's capability to both prevent and reverse liver fibrosis sustained by a significant reduction of pro‐fibrogenic genes as TGF‐β and CTGF encouraged us to assess GHRP6's potential to prevent exuberant scarring in the classic rabbit model of HTS induction. We recently published the first preliminary evidence that, as expected, GHRP6 did prevent the onset of experimental HTS …”

“…We recently published the first preliminary evidence that, as expected, GHRP6 did prevent the onset of experimental HTS. 9 Here, we thoroughly evaluated GHRP6 consistency in both the prevention and reversion of HTS in the experimental rabbit model. For the first time, we used ultrasonographic procedures to characterise experimental HTS, and we acquired the earliest relevant mechanistic proteome data supporting the anti-fibrogenic effects of GHRP6.…”