The influence of a synthetic growth hormone‐releasing hormone analogue G11 and opioid peptide biphalin on selected fibroblasts parameters relevant to wound healing

The treatment of hard-to-heal chronic wounds is still a major medical problem and aneconomic and social burden. In this work, we examine the proregenerative potentialof two peptides, G11 (a trypsin-resistant analogue of growth hormone-releasing hor-mone [GHRH]) and biphalin (opioid peptide), and their combination in vitro on humanfibroblasts (BJ). G11, biphalin and their combination exhibited no toxicity against BJcells. On the contrary, these treatments significantly stimulated proliferation andmigration of fibroblasts. Under inflammatory conditions (LPS-induced BJ cells), wenoticed that the tested peptides decreased the levels of cyclooxygenase-2 (COX-2),inducible nitric oxide synthase (iNOS) and interleukin 1β(IL-1β). This was correlatedwith diminished phosphorylation levels of p38 kinase, but not those of ERK1/2. Wefound also that G11, biphalin and their combination activated the ERK1/2 signallingpathway, which has been previously implicated in promigratory activity of someregeneration enhancers, including opioids or GHRH analogues. Potential applicationof their combination requires further work, in particular in vivo experiments, in whichthe organism-level relevance of the discussed cell-level effects would be proven and,additionally, analgesic action of the opioid ingredient could be quantified.