Citrullyl-Hydroxyprolyl-Proline (ChPP): An Artificially Synthesized Tripeptide as Potent ACE Inhibitor
Tóm tắt
Currently bioactive peptides are the main focus in attempts to identify novel angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of hypertension due to their fewer side effects. In the present study we aimed to investigate the antihypertensive activity of 4 synthetic tripeptides Ornithyl-Hydroxyprolyl-Proline (Orn-Hyp-Pro OhPP) Ornithyl-Prolyl-Hydroxyproline (Orn-Pro-Hyp OPhP) Citrullyl-Hydroxyprolyl-Proline (Cit-Hyp-Pro ChPP) and Citrullyl-Prolyl-Hydroxyproline (Cit-Pro-Hyp CPhP) in vitro and in vivo. The ACE inhibitory activity and mode were analyzed with a modified spectrophotometric method and Lineweaver-Burk plots respectively. It showed that peptide Citn-Hyp-Pro (ChPP) exhibited the highest inhibition potency with an IC50 value of 40.48 μM and displayed a competitive inhibition of ACE. Molecular docking simulations suggested that ChPP could form several critical hydrogen bonds with the major residues His353 and His513 located in the S2 active site of ACE. The systolic blood pressure of spontaneously hypertensive rats monitored by the tail-cuff method was significantly reduced by 15.54% at 4 h after oral administration of 20 mg/kg BW ChPP. Also ChPP remarkably downregulated the angiotensin II receptor type 1 (agtr1) and miR-132/-212 levels in SHRs which was similar to that observed in SHRs treated with captopril. It showed us that the tripeptide ChPP could be explored as a promising ACE inhibitor (ACEI) for treatment of hypertension.
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