Activation of transient receptor potential channels is involved in reactive oxygen species (ROS)-dependent regulation of blood flow by (-)-epicatechin tetramer cinnamtannin A2

Taiki Fushimi, Chie Hirahata, Kento Hiroki, Yasuyuki Fujii, Vittorio Calabrese, Yoshitomo Suhara, Naomi Osakabe

Research output: Contribution to journalArticlepeer-review

Abstract

Intervention trials confirmed that blood flow-mediated dilatation increases significantly after intake of astringent (-)-epicatechin (EC) oligomers (procyanidins)-rich foods, but the mechanism remains unclear. We have previously found that procyanidins can activate the sympathetic nervous and subsequently increase blood flow. Here, we examined whether procyanidin-derived reactive oxygen species (ROS) activate transient receptor potential (TRP) channels in gastrointestinal sensory nerves and consequently induce sympathoexcitation. We evaluated the redox properties of EC and its tetramer cinntamtannin A2 (A2) at pH 5 or 7, mimicking plant vacuole or oral cavity/small intestine using a luminescent probe. At pH 5, A2 or EC showed O2·- scavenging ability, but they promoted O2·- generation at pH 7. We observed blood flow in rat cremaster arterioles using laser Doppler, a single oral dose of 10 µg/kg A2 markedly increased blood flow, while EC showed little activity. This change with A2 was significantly dampened by co-administration of adrenaline blocker, ROS scavenger N-acetyl-L-cysteine (NAC), TRP vanilloid 1, or ankyrin 1 antagonist. We also performed a docking simulation of EC or A2 with the binding site of a typical ligand for each TRP channel and calculated the respective binding affinities. The binding energies were notably higher for A2 than typical ligands, suggesting that A2 is less likely to bind to these sites. ROS produced at neutral pH following the orally administered A2 to the gastrointestinal tract could activate TRP channels, triggering sympathetic hyperactivation and causing hemodynamic changes.

Original languageEnglish
Article number115682
JournalBiochemical Pharmacology
Volume214
DOIs
Publication statusPublished - 2023 Aug

Keywords

  • Cinnamtannin A2
  • Hemodynamics
  • Redox property
  • Transient receptor potential

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Fingerprint

Dive into the research topics of 'Activation of transient receptor potential channels is involved in reactive oxygen species (ROS)-dependent regulation of blood flow by (-)-epicatechin tetramer cinnamtannin A2'. Together they form a unique fingerprint.

Cite this