Effects of KKRRPGP (Lys-Lys-Arg-Arg-Pro-Gly-Pro) and KRRKPGP (Lys-Arg-Arg-Lys-Pro-Gly-Pro) peptides on hemostasis parameters, lipid profile, blood glucose level, and body weight changes in rats with metabolyc syndrome and endothelial dysfunction

Lysine-and arginine-containing peptides Lys-Lys-Arg-Arg-Pro-Gly-Pro and Lys-Arg-Arg-LysPro-Gly-Pro were administered intranasal way (daily single dose of 100 mcg/kg for 7 days) to animals (laboratory rats) with experimental metabolic syndrome and endothelial dysfunction. Metabolic syndrome was modeled by a high-calorie diet throughout the experiment period, and endothelial dysfunction was modeled by intraperitoneal injection of L-NAME (daily single dose of 10 mg/kg for 5 days). It was found that these peptides had anti-clotting, hypoglycemic, and hypocholesterol effects and reduced body weight gain in experimental animals. Peptides treatments affected both primary (vascular-platelet) hemostasis, reducing platelet aggregation, and all links of plasma hemostasis, increasing anticoagulant, fibrindepolymerization and enzymatic fibrinolytic activity, as well as antifibrinstabilizing properties of plasma and reducing the concentration of fibrinogen in it. At the same time, the studied peptides reduced the content of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, increasing the concentration of high-density lipoprotein cholesterol. These effects were observed 20 hrs after the last administration of peptides and persisted, although to a lesser extent, 7 days (168 hrs) after stopping treatment. In this regard, we can talk about the prolonged action of both glyproline peptides, which have lysine and arginine amino acid residues in their structure, and their ability to protect the body from the development of metabolic diseases and endothelial dysfunction. The maximum effects  were provided by the LysArg-Arg-Lys-Pro-Gly-Pro peptide, which may be due to its structural features.

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