Bioavailability and Metabolism of Bioactive Peptide IRW with Angiotensin-Converting Enzyme 2 (ACE2) Upregulatory Activity in Spontaneously Hypertensive Rats

Zihan Wang, Chu Fan Wang, Hongbing Fan, Xiaoyu Bao, Fatemeh Ashkar, Liang Li, Tony K.L. Kiang, Jianping Wu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Peptide IRW is the first food-derived angiotensin-converting enzyme 2 (ACE2) upregulator. This study aimed to investigate the pharmacokinetic characteristics of IRW and identify the metabolites contributing to its antihypertensive activity in spontaneously hypertensive rats (SHRs). Rats were administered 100 mg of IRW/kg of the body weight via an intragastric or intravenous route. The bioavailability (F %) was determined to be 11.7%, and the half-lives were 7.9 ± 0.5 and 28.5 ± 6.8 min for gavage and injection, respectively. Interestingly, significant blood pressure reduction was not observed until 1.5 h post oral administration, or 2 h post injection, indicating that the peptide’s metabolites are likely responsible for the blood pressure-lowering activity. Time-course metabolomics revealed a significant increase in the level of kynurenine, a tryptophan metabolite, in blood after IRW administration. Kynurenine increased the level of ACE2 in cells. Oral administration of tryptophan (W), but not dipeptide IR, lowered the blood pressure and upregulated aortic ACE2 in SHRs. Our study supports the key role of tryptophan and its metabolite, kynurenine, in IRW’s blood pressure-lowering effects.

Original languageEnglish
Pages (from-to)8606-8617
Number of pages12
JournalJournal of Agricultural and Food Chemistry
Volume72
Issue number15
DOIs
StatePublished - Apr 17 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

Keywords

  • angiotensin-converting enzyme 2
  • bioactive peptide
  • bioavailability
  • IRW
  • metabolomics
  • spontaneously hypertensive rats

ASJC Scopus subject areas

  • General Chemistry
  • General Agricultural and Biological Sciences

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