ABSTRACT
The study examined the antihypertensive effect of peptides derived from pepsin-hydrolyzed corn gluten meal, namely KQLLGY and PPYPW, and their in silico gastrointestinal tract digested fragments, KQL and PPY, respectively. KQLLGY and PPYPW showed higher angiotensin I-converting enzyme (ACE)-inhibitory activity and lower ACE inhibition constant (Ki) values when compared to KQL and PPY. Only KQL showed a mild antihypertensive effect in spontaneously hypertensive rats with -7.83 and - 5.71 mmHg systolic and diastolic blood pressure values, respectively, after 8 h oral administration. During passage through Caco-2 cells, KQL was further degraded to QL, which had reduced ACE inhibitory activity. In addition, molecular dynamics revealed that the QL-ACE complex was less stable compared to the KQL-ACE. This study reveals that structural transformation during peptide permeation plays a vital role in attenuating antihypertensive effect of the ACE inhibitor peptide.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Antihypertensive Agents , Peptidyl-Dipeptidase A , Zea mays , Animals , Humans , Male , Rats , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/metabolism , Antihypertensive Agents/chemistry , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Caco-2 Cells , Digestion/drug effects , Gastrointestinal Tract/metabolism , Glutens/chemistry , Glutens/metabolism , Hydrolysis , Hypertension/metabolism , Hypertension/drug therapy , Hypertension/physiopathology , Peptides/chemistry , Peptides/pharmacology , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Hydrolysates/chemistry , Protein Hydrolysates/pharmacology , Rats, Inbred SHR , Zea mays/chemistry , Zea mays/metabolismABSTRACT
Inhibition of digestive enzymes such as α-amylase and pancreatic lipase (PL) is a promising therapeutic strategy for the treatment and management of chronic health conditions such as diabetes and obesity. Therefore, the aim of this work was to determine the enzyme inhibitory activity of polyphenol-rich aqueous extracts of Amaranthus viridis (AV), Solanum macrocarpon (SM) and Telfairia occidentalis (TO) leaves, which were harvested from plants produced using multiple urea fertilizer doses (0-80 kg N/ha). Fertilizer application was applied at two time points (at planting or 2 weeks after seedling emergence). Leaf extracts were obtained using aqueous extraction (1:20, leaves:water) for 4 h at 60°C followed by centrifugation and freeze-drying of the supernatant. Results showed that the extracts inhibited α-amylase, and pancreatic lipase dose-dependently with TO extracts having significantly (p < 0.05) higher inhibitory activities for both enzymes. Fluorescence intensity and circular dichroism spectra in the presence and absence of leaf extracts indicate significant changes to the enzyme protein secondary and tertiary conformations. We conclude that the leaf extracts, especially from TO are potential agents for reducing calorie intake as a preventive or treatment tool against chronic diseases such as diabetes and obesity.