Protease inhibition has led to treating many diseases and has been successful in producing many commercial drugs by pharmaceutical companies. Among many proteases, serine protease has been attractive in treating metabolic disorder diabetes mellitus (DM). Gliptins have been proven to inhibit dipeptidyl peptidase-4 (DPP4), a serine protease, and are an emerging therapeutic drug target to reduce blood glucose levels, but until now there is no natural cyclic peptide proven to inhibit serine protease DPP4. This study demonstrates the potential mechanism of natural cyclic peptide oxytocin (OXT) as a DPP4 inhibitor. To achieve this, initially, activity atlas and field-based models of DPP4 inhibitors were utilized to predict the possible features of positive and negative electrostatic, hydrophobic, and activity shapes of DPP4 inhibition. Oxytocin binding mode, flexibility, and interacting residues were studied using molecular docking simulations studies. 3D-RISM calculations studies revealed that the stability of water molecules at the binding site are favorable. Finally, an experimental study using fluorescence assay revealed OXT inhibits DPP4 in a concentration-dependent manner in a significant way (p < 0.05) and possess IC50 of 110.7 nM. These new findings significantly expand the pharmaceutical application of cyclic peptides, and in specific OXT, and implicate further optimization of OXT inhibition capacity to understand the effect of DPP4 inhibition. This work highlights the development of natural cyclic peptides as future therapeutic peptides to reduce glucose levels and treat diabetes mellitus.

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ABSTRACT. The objective of this study was to analyze the effect of an electric field treatment (voltage: 3 kV cm -1 , frequency: 60 Hz and time: of 5 and 25 min) on the stability of unsaturated fatty acids in virgin olive oil. Unsaturated fatty acid oxidation in the virgin olive oil was analyzed by Fourier transform infrared spectroscopy in the mid infrared region, and by quality parameters (acidity, peroxide and iodine). The electric field is a suitable method to preserve this oil composition with minimal modifications without the synthetic antioxidant addition.

Functionalized single-walled carbon nanotubes with polyethylene glycol (PEGylated SWCNTs) are a promising nanomaterial that recently has emerged as the most attractive “cargo” to deliver chemicals, peptides, DNA and RNAs into cells. Insulin therapy is a recommended therapy to treat diabetes mellitus despite its side effects. Recently, functional dispersion made up of bioactive peptides, bioactive compounds and functionalized carbon nanomaterials such as PEGylated SWCNTs have proved to possess promising applications in nanomedicine. In the present study, molecular modeling simulations are utilized to assist in designing insulin hormone-PEGylated SWCNT composites, also called functional dispersion; to achieve this experimentally, an ultrasonication tool was utilized. Enzymatic degradation assay revealed that the designed functional dispersion protects about 70% of free insulin from pepsin. In addition, sulforhodamine B (SRB) assay, the quantification of insulin and glucose levels in differentiated skeletal muscle cell supernatants, reveals that functional dispersion regulates glucose and insulin levels to promote skeletal muscle cell proliferation. These findings offer new perspectives for designed functional dispersion, as potential pharmaceutical preparations to improve insulin therapy and promote skeletal muscle cell health.