Nephroprotective peptides of Laennec® in the context of pharmacotherapy for nephro-hepato-metabolic disorders

Abstract

Background. Renal-hepatic dysfunction, which often occurs in liver dysfunction, requires the use of effective and safe nephroprotective agents. Human placenta hydrolysates (HPH) are hepatoprotectors, but little is known about HPH nephroprotective properties and the molecular mechanisms of their implementation.Objective: identification of potential molecular mechanisms of Laennec® HPH neuroprotective action based on bioinformatic analysis of collected mass spectrometric data.Material and methods. Methods of proteomic analysis of peptide preparations were used. The analysis of Laennec® HPH peptide composition included four stages: drug purification, chromatographic separation of peptides, determination of the multidimensional mass spectrum of peptide fraction and de novo sequencing of the isolated peptides.Results. The study of Laennec® HPH peptide composition allowed to identify 48 peptides that can exhibit nephroprotective effects. It was shown that HPH contains biologically active fragments of nephroprotective adrenomedullins, inhibitor peptides of a number of kinases (FYN, SHH, WNK1/4, SGK1, IRAK4, ROCK1/2) and fibrogenic receptors (PDGFR, TGFB1I1).Conclusion. By inhibiting the listed target proteins, HPH peptides provide nephroprotection through reducing inflammation, anti-stress effects and preventing fibrotic changes in kidney tissue