Natural Antioxidants as Regulators of Circular RNA Expression and Function

Abstract

Circular RNAs (circRNAs) are a class of noncoding RNAs characterized by covalently closed loop structures that confer high stability and diverse regulatory functions. Emerging evidence suggests that circRNAs modulate gene expression by acting as miRNA sponges, interacting with RNA-binding proteins (RBPs), influencing transcription, and serving as translational templates. Their dysregulation has been linked to various diseases, including cancer, cardiovascular, neurodegenerative, and metabolic disorders. Oxidative stress, a common hallmark in these pathologies, can alter circRNA expression and function. Natural antioxidants, derived from dietary sources such as fruits, vegetables, herbs, and medicinal plants, offer a promising approach for restoring redox homeostasis and influencing the regulation of circRNA networks. This review provides a comprehensive overview of how different classes of natural antioxidants, including flavonoids, polyphenols, carotenoids, terpenoids, vitamins, and alkaloids, modulate circRNA expression and function in various disease contexts. Representative compounds such as quercetin, curcumin, resveratrol, astaxanthin, kaempferol, and genistein exhibit circRNA-mediated actions that impact oxidative stress, inflammation, cell proliferation, apoptosis, and differentiation. The molecular mechanisms involve circRNA–miRNA–mRNA axes, interactions with RBPs, and modulation of epigenetic regulators and signaling pathways. We also discuss key challenges, including limited mechanistic understanding, bioavailability constraints, and the need for in vivo validation. Future perspectives emphasize the integration of antioxidant therapy with RNA-targeted approaches, advanced delivery systems, and personalized profiling of circRNA. Collectively, the regulatory interplay between natural antioxidants and circRNAs represents a promising frontier in redox biology and RNA-based therapeutics. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA Interactions RNA in Disease and Development > RNA in Disease.