Metabolomic signature in ocular dosing: Exploring the metabolic impacts of sublethal high-dose naringenin on ARPE-19 cells

Abstract

Introduction

Naringenin (NRG), a flavanone polyphenol found in citrus fruits, has been increasingly recognized for its potential therapeutic effects in ocular disorders. This study aimed to assess the impact of high-dose NRG on human retinal pigment epithelial cells (ARPE-19) cells through metabolomic analysis.

Methods

Cell viability was evaluated using the thiazolyl blue tetrazolium bromide (MTT) assay, demonstrating non-cytotoxicity at concentrations ranging from 3 to 100 μM within a 24-h exposure period. High-dose (100 μM) NRG was selected for further investigation based on its non-cytotoxic nature. Chromatographic analyses were performed using Liquid Chromatography Quadropole Time-of-Flight Mass Spectrometry (LC-Q-ToF-MS).

Results

Metabolomic analysis revealed subtle metabolic changes, with similar profiles between control and test groups, emphasizing the nuanced effects of NRG. Multivariate analysis, including Principal Component Analysis (PCA), illustrated distinct clustering of control and test groups, indicating consistent metabolic adjustments within each group. Despite maintaining cell viability, stress responses were identified in ARPE-19 cells, as evidenced by reduced glucose-6-phosphate levels and alterations in pyrimidine/purine pathways. This highlights the importance of exploring cellular responses using metabolomics beyond traditional viability metrics.

Conclusion

In the broader context, this study contributes data on the interplay between NRG and retinal pigmented epithelial. As NRG is utilized in routine ocular applications, particularly as an eye drop, our findings suggest careful dosage selection, considering both non-irritability and subtle metabolic changes. Further research is needed to refine dosage strategies and comprehensively assess the safety profile of NRG in ocular applications.