Anti-hypertensive and angiotensin-converting enzyme inhibitory effects of Radix Astragali and its bioactive peptide AM-1

J Ethnopharmacol. 2020 May 23:254:112724. doi: 10.1016/j.jep.2020.112724. Epub 2020 Feb 28.

Abstract

Ethnopharmacological relevance: Hypertension is one of the common chronic health problems in the world. Astragalus membranaceus root (AM), also known as Huangqi, is a popular medicinal herb traditionally used to reinforce vital energy and modulate hypertension.

Aim of the study: This study was to reveal the anti-hypertensive activities and mechanisms of AM in spontaneously hypertensive rats (SHRs). Moreover, the presence of bioactive components in AM was further identified.

Materials and methods: We analyzed the effects of aqueous extract of AM (AME) on the regulation of blood pressure and angiotensin converting enzyme (ACE), the major target of anti-hypertensive drugs. Proteomic, bioinformatics, and docking analyses were performed to identify the anti-hypertensive bioactive peptides in AME.

Results: Our data showed that AME inhibited ACE activities in a dose-dependent manner, with an IC50 of 1.85 ± 0.01 μg/ml. In comparison with mock, oral administration of AME reduced systolic blood pressure (SBP) levels in SHRs, and the level of SBP was decreased by 22.33 ± 3.61 mmHg at 200 mg/kg AME. Proteomic analysis identified that an abundant 152-amino-acid putative protein kinase fragment accounted for approximately 11.7% of protein spots in AME. AM-1 (LVPPHA), a gastrointestinal enzyme-resistant peptide cleaved from putative protein kinase fragment, inhibited ACE activities, with an IC50 value of 414.88 ± 41.88 μM. Moreover, oral administration of AM-1 significantly decreased SBP levels by 42 ± 2.65 mmHg at 10 μmol/kg. Docking analysis further showed that AM-1 docked into the active site channel of ACE and interacted with Ala-354 in the active site pocket of ACE.

Conclusions: the ACE inhibitory effect of AM and the presence of ACE inhibitory phytopeptide in AME supported the ethnomedical use of AM on hypertension.

Keywords: Angiotensin-converting enzyme; Astragalus membranaceus; Bioactive peptide; Hypertension.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Astragalus propinquus
  • Blood Pressure / drug effects
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Hypertension / drug therapy*
  • Male
  • Mice, Inbred BALB C
  • Molecular Docking Simulation
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Peptidyl-Dipeptidase A / metabolism
  • Rats, Inbred SHR

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Drugs, Chinese Herbal
  • Peptides
  • Huang Qi
  • Peptidyl-Dipeptidase A