Ferulic acid attenuates high glucose-induced apoptosis in retinal pigment epithelium cells and protects retina in db/db mice

PeerJ. 2022 May 31:10:e13375. doi: 10.7717/peerj.13375. eCollection 2022.

Abstract

Background: Herein, we aimed to present evidence that Ferulic acid (FA), a phenolic acid, can alleviate high glucose (HG)-induced retinal pigment epithelium (RPE) cell apoptosis and protect retina in db/db mice.

Methods: ARPE-19 cells (a human RPE cell line) were divided into four groups: control group; HG group (30 mmol/L glucose); HG+FA group (30 mmol/L glucose and 10 mmol/L FA). Cell viability and apoptosis were detected using CCK-8 and Annexin-5 staining, respectively. Apoptosis-related markers including P53, BAX and Bcl2 were examined by RT-qPCR, western blot and immunohistochemistry. Totally, 30 male db/db mice were randomly divided into db/db group (5 ml/kg saline) and FA group (0.05 g/kg FA). After treatment for 2 months, retinal samples were subjected to hematoxylin and eosin (H&E) and Masson staining. Moreover, immunofluorescence was used to detect apoptosis-related markers. Blood samples were collected for measuring cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels.

Results: FA treatment markedly increased cell viability and suppressed cell apoptosis of ARPE-19 cells compared to the HG-exposed group. Furthermore, FA ameliorated the abnormal expression levels of P53, BAX and Bcl2 in HG-induced ARPE-19 cells. In animal models, FA attenuated pathological changes in the retina tissues of diabetic mice. Consistent with in vitro models, FA significantly ameliorated the expression of apoptosis-related markers in retina tissues. Biochemical test results showed that FA reduced hyperlipidemia in diabetic mice.

Conclusion: Our findings suggest that FA alleviates HG-induced apoptosis in RPE cells and protects retina in db/db mice, which can be associated with P53 and BAX inactivation and Bcl2 activation.

Keywords: ARPE-19 cells; Apoptosis; Diabetic retinopathy; Ferulic acid; High glucose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Diabetes Mellitus, Experimental* / drug therapy
  • Glucose / toxicity
  • Humans
  • Male
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Retina / metabolism
  • Retinal Pigment Epithelium*
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / genetics

Substances

  • ferulic acid
  • bcl-2-Associated X Protein
  • Tumor Suppressor Protein p53
  • Glucose
  • Proto-Oncogene Proteins c-bcl-2

Grants and funding

This work was funded by the Natural Science Foundation of Ningxia Hui Autonomous Region (2018AAC03176), the Ningxia Blind Eye Disease Clinical Medical Research Center Innovation Platform Project, and the Ningxia Hui Autonomous Region Key R&D Plan Project in 2021 (2021BEG03110). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.