A Major Intestinal Catabolite of Quercetin Glycosides, 3‐Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde‐Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity

Yujia Liu, Takumi Myojin, Kexin Li, Ayuki Kurita, Masayuki Seto, Ayano Motoyama, Xiaoyang Liu, Ayano Satoh, Shintaro Munemasa, Yoshiyuki Murata, Toshiyuki Nakamura, Yoshimasa Nakamura

Research output: Contribution to journalArticlepeer-review

Abstract

Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol‐induced chronic diseases. Here, we evaluated the modulating effects of 3‐hydroxyphenyla-cetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde‐induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR‐dependent reporter gene expression, though not the nuclear factor erythroid‐2‐ related factor 2 (Nrf2)‐dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde‐induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde‐induced cytotoxicity, mainly through the AhR‐dependent and Nrf2‐independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol‐induced chronic diseases.

Original languageEnglish
Article number1762
JournalInternational journal of molecular sciences
Volume23
Issue number3
DOIs
Publication statusPublished - Feb 1 2022

Keywords

  • 3‐hydroxyphenylacetic acid
  • Acetaldehyde
  • Aldehyde dehydrogenase
  • Aryl hydrocarbon receptor
  • Quercetin metabolites

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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