Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Anita Kirti Ghosh
ORCID logo ,
Rubina Thapa
,
Harsh Nilesh Hariani
ORCID logo ,
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
* ORCID logo
Version 1 : Received: 6 April 2021 / Approved: 8 April 2021 / Online: 8 April 2021 (09:09:24 CEST)

A peer-reviewed article of this Preprint also exists.

Ghosh, A.K.; Thapa, R.; Hariani, H.N.; Volyanyuk, M.; Ogle, S.D.; Orloff, K.A.; Ankireddy, S.; Lai, K.; Žiniauskaitė, A.; Stubbs, E.B.; et al. Poly(Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress. Pharmaceutics 2021, 13, 1362, doi:10.3390/pharmaceutics13091362. Ghosh, A.K.; Thapa, R.; Hariani, H.N.; Volyanyuk, M.; Ogle, S.D.; Orloff, K.A.; Ankireddy, S.; Lai, K.; Žiniauskaitė, A.; Stubbs, E.B.; et al. Poly(Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress. Pharmaceutics 2021, 13, 1362, doi:10.3390/pharmaceutics13091362.

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.

Keywords

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

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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