Hawthorn polyphenols reduce high glucose-induced inflammation and apoptosis in ARPE-19 cells by regulating miR-34a/SIRT1 to reduce acetylation

J Food Biochem. 2021 Feb;45(2):e13623. doi: 10.1111/jfbc.13623. Epub 2021 Jan 24.

Abstract

Diabetic retinopathy is a major complication in patients with diabetes. Herein, we investigate how hawthorn polyphenol extract (HPE) affects high glucose-induced oxidation, inflammation, and apoptosis in ARPE-19 cells. HPLC-MS/MS was used to determine HPE content and composition. Reactive oxygen species (ROS) production was assessed using fluorescence microscopy, while glucose-induced gene and protein expressions were analyzed using real-time PCR and western blotting in cells transfected with miR-34a mimics. We found that treating cells with 10 μg/ml of HPE, 30 μM procyanidin B2, chlorogenic acid, epicatechin, or resveratrol (positive control) significantly reduced ROS production and decreased apoptosis and inflammation-related factors (p < .01). Moreover, the expression level of SIRT1 was increased, while that of acetylated NF-κB p65 and p53 proteins was decreased. These data suggest that HPE can inhibit oxidative damage, inflammation, and apoptosis through the AMPK/SIRT1/NF-κB pathway, and decrease miR-34a/SIRT1/p53 pathway activation in ARPE-19 cells, thereby demonstrating a potential use as a food additive to mitigate hyperglycemia-induced retinal damage. PRACTICAL APPLICATIONS: Hawthorn polyphenol extract (HPE) significantly reduced ROS levels, apoptosis, and the expression of inflammation-related factors in ARPE-19 cells. HPE also inhibited the AMPK/SIRT1/NF-κB and miR-34a/SIRT1/p53 pathways, which are involved in hyperglycemia-induced inflammation and apoptosis of ARPE-19 cells by regulating acetylation. Thus, HPE, as a potential food additive, may mitigate hyperglycemia-induced retinal damage.

Keywords: ARPE-19 cells; Hawthorn polyphenol; hyperglycemia; miR-34a; protein acetylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Apoptosis
  • Crataegus*
  • Glucose / toxicity
  • Humans
  • Inflammation / drug therapy
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Polyphenols / pharmacology
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Tandem Mass Spectrometry

Substances

  • MicroRNAs
  • Polyphenols
  • SIRT1 protein, human
  • Sirtuin 1
  • Glucose