Licochalcone A Attenuates Oxidative Stress and Inflammation to Promote Second-Degree Burn Healing Through Nrf2/HO-1 Activation in Mice
- 1Department of Biochemistry and Molecular Biology, College of Life Science and Technology, The State Key Laboratory Incubation Base for Conservation and Utilization of Bio-Resource in the Tarim Basin of the Xinjiang Production and Construction Corps, Tarim University, Alar 843300, China
Abstract
Burn injury represents one of the most prevalent accidental traumas worldwide, contributing to substantial morbidity and mortality. Second-degree burns are frequently complicated by bacterial infection, excessive inflammation, and oxidative stress, which collectively impede wound healing. Licochalcone A (LCA), a bioactive flavonoid isolated from licorice, exhibits anti-inflammatory and antioxidant properties, yet its therapeutic role in burn wounds remains unexplored. Here, we evaluated the effects of a topical LCA-containing hydrogel on wound healing in a mouse dorsal second-degree scald model (100 °C, 5 s) and explored the associated molecular changes. In vivo, LCA-hydrogel treatment was associated with increased collagen deposition, reduced expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), reduced neutrophil and macrophage infiltration, and upregulated Ki67 and vascular endothelial growth factor C (VEGF-C). In hydrogen peroxide (H2O2)-stimulated fibroblasts, LCA attenuated reactive oxygen species (ROS) accumulation, improved cell viability and migration, preserved mitochondrial integrity, and restored antioxidant enzyme activities. Integrated transcriptomic and proteomic analyses identified 227 co-differentially expressed genes/proteins enriched in the reactive oxygen species pathway. Western blotting showed that the effects of LCA were associated with increased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression and decreased Kelch-like ECH-associated protein (Keap1) expression. These exploratory findings suggest that the LCA-containing hydrogel is associated with accelerated second-degree burn healing, and that the antioxidant effects of LCA are associated with modulation of Keap1/Nrf2/HO-1 signaling, supporting further evaluation of its potential as a burn therapeutic candidate.
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BibTeX
@article{xu2026licochalcone,
title = {{Licochalcone A Attenuates Oxidative Stress and Inflammation to Promote Second-Degree Burn Healing Through Nrf2/HO-1 Activation in Mice}},
author = {Menglong Xu and Hangzhen Zhou and Shuwei Li and Yongchao Li and Qinqin Wang and Haocheng Guan and Xiaoxia Luo},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219450},
url = {https://www.mdpi.com/1422-0067/27/21/9450},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Licochalcone A Attenuates Oxidative Stress and Inflammation to Promote Second-Degree Burn Healing Through Nrf2/HO-1 Activation in Mice
AU - Menglong Xu
AU - Hangzhen Zhou
AU - Shuwei Li
AU - Yongchao Li
AU - Qinqin Wang
AU - Haocheng Guan
AU - Xiaoxia Luo
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219450
UR - https://www.mdpi.com/1422-0067/27/21/9450
AB - Burn injury represents one of the most prevalent accidental traumas worldwide, contributing to substantial morbidity and mortality. Second-degree burns are frequently complicated by bacterial infection, excessive inflammation, and oxidative stress, which collectively impede wound healing. Licochalcone A (LCA), a bioactive flavonoid isolated from licorice, exhibits anti-inflammatory and antioxidant properties, yet its therapeutic role in burn wounds remains unexplored. Here, we evaluated the effects of a topical LCA-containing hydrogel on wound healing in a mouse dorsal second-degree scald model (100 °C, 5 s) and explored the associated molecular changes. In vivo, LCA-hydrogel treatment was associated with increased collagen deposition, reduced expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), reduced neutrophil and macrophage infiltration, and upregulated Ki67 and vascular endothelial growth factor C (VEGF-C). In hydrogen peroxide (H2O2)-stimulated fibroblasts, LCA attenuated reactive oxygen species (ROS) accumulation, improved cell viability and migration, preserved mitochondrial integrity, and restored antioxidant enzyme activities. Integrated transcriptomic and proteomic analyses identified 227 co-differentially expressed genes/proteins enriched in the reactive oxygen species pathway. Western blotting showed that the effects of LCA were associated with increased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression and decreased Kelch-like ECH-associated protein (Keap1) expression. These exploratory findings suggest that the LCA-containing hydrogel is associated with accelerated second-degree burn healing, and that the antioxidant effects of LCA are associated with modulation of Keap1/Nrf2/HO-1 signaling, supporting further evaluation of its potential as a burn therapeutic candidate.
SN - 1422-0067
ER -