Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antioxidant Effects of the Prenylated Flavonoid, Xanthohumol, on Corneal Epithelial Cells in Experimental Dry Eye Disease

Version 1 : Received: 6 April 2021 / Approved: 8 April 2021 / Online: 8 April 2021 (09:09:24 CEST)

How to cite: Ghosh, A.K.; Thapa, R.; Hariani, H.N.; Volyanyuk, M.; Orloff, K.A.; Ankireddy, S.; Lai, K.; Ziniauskaite, A.; Stubbs Jr, E.B.; Kalesnykas, G.; Hakkarainen, J.J.; Langert, K.A.; Kaja, S. Antioxidant Effects of the Prenylated Flavonoid, Xanthohumol, on Corneal Epithelial Cells in Experimental Dry Eye Disease. Preprints 2021, 2021040222 (doi: 10.20944/preprints202104.0222.v1). Ghosh, A.K.; Thapa, R.; Hariani, H.N.; Volyanyuk, M.; Orloff, K.A.; Ankireddy, S.; Lai, K.; Ziniauskaite, A.; Stubbs Jr, E.B.; Kalesnykas, G.; Hakkarainen, J.J.; Langert, K.A.; Kaja, S. Antioxidant Effects of the Prenylated Flavonoid, Xanthohumol, on Corneal Epithelial Cells in Experimental Dry Eye Disease. Preprints 2021, 2021040222 (doi: 10.20944/preprints202104.0222.v1).

Abstract

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

Subject Areas

ocular surface disease; dry eye disease; antioxidant; Xanthohumol; drug delivery; drug formulation; PLGA; nanoparticles

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