Abstract
PURPOSE: Liquiritigenin (LIQ), an active flavanone derived from Glycyrrhiza uralensis, is known to possess potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidative and anti-inflammatory effects of LIQ on experimental dry eye disease (DED) models. MATERIALS AND METHODS: In vitro effects of LIQ were assessed using a hyperosmotic stress model with assays including quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and immunofluorescent staining. The antioxidative effect was compared with n-acetyl cysteine (NAC) and the anti-inflammatory effect with dexamethasone (DEX). In vivo, DED was induced by desiccation stress in a controlled environmental chamber mouse model. Tear production rate, corneal staining scores, pro-inflammatory cytokine expression, conjunctival goblet cell density, infiltration of T-helper (Th) 17 cells, and reactive oxygen species (ROS) levels in the lacrimal gland were evaluated. RESULTS: In vitro studies demonstrated that LIQ significantly reduced ROS levels, comparable to NAC, and exhibited anti-inflammatory effects similar to DEX. In the mouse model, LIQ treatment significantly increased tear production and reduced corneal staining scores compared to controls, decreased the expression of Interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-13, tumor necrosis factor α, Interferon γ, restored conjunctival goblet cell density, reduced Th17 cell infiltration, and lowered ROS levels in the lacrimal gland Microarray analysis revealed LIQ regulated cytokine expression and ROS levels through the modulation of the aldo-keto reductase (AKR) superfamily in hyperosmotic stress conditions. CONCLUSION: LIQ shows potential as a therapeutic agent for DED through its dual anti-inflammatory and antioxidative actions, primarily through modulation of the AKR superfamily.