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

Anita Kirti Ghosh; Rubina Thapa; Harsh Nilesh Hariani; Michael Volyanyuk; Karoline Anne Orloff; Samatha Ankireddy; Karen Lai; Agne Ziniauskaite; Evan Benjamin Stubbs Jr; Giedrius Kalesnykas; Jenni Johanna Hakkarainen; Kelly Ann Langert; Simon Kaja

doi:10.20944/preprints202104.0222.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

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.

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

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

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