ORIGINAL PAPER
Puerarin alleviates oxidative stress-induced mitochondrial dysfunction in human lens epithelial cells through modulation of DLG1 expression
1
Ophthalmology Medical Center, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, 241000, People’s Republic of China
These authors had equal contribution to this work
Submission date: 2025-11-08
Final revision date: 2026-03-20
Acceptance date: 2026-04-14
Online publication date: 2026-07-24
Corresponding author
Shaoxin Pan
Ophthalmology Medical Center, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, 241000, People’s Republic of China
Ophthalmology Medical Center, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, 241000, People’s Republic of China
KEYWORDS
Oxidative stressPuerarinMitochondrial dysfunctionHuman lens epithelial cellsAge-related cataractsDLG1
ABSTRACT
Introduction:
Oxidative stress and mitochondrial dysfunction are key contributors to age-related cataract (ARC) development. This study investigated the role of DLG1 in oxidative injury in human lens epithelial cells (HLECs) and whether puerarin (Pue) could alleviate oxidative stress and mitochondrial dysfunction.
Material and Methods:
Gene co-expression networks were constructed for differentially expressed genes (DEGs) in GSE3040 along with GSE213546. Expression, diagnostic performance, and enrichment analyses were performed on the overlapping genes in the two datasets. Functional assays were performed in hydrogen peroxide (H2O2)-induced HLECs to evaluate the role of DLG1 and Pue’s impact on oxidative stress and mitochondrial function.
Results:
DLG1, histone H4 (HIST1H4L), N alpha acetyltransferase 16 (NAA16), and Scratch family transcriptional repressor 1 (SCRT1) were consistently upregulated in ARC and exhibited high diagnostic performance. In HLECs, H2O2 increased the mRNA levels of all four genes, whereas co-treatment with Pue reversed these changes. Functionally, small interfering RNA (siRNA)-mediated DLG1 silencing mitigated oxidative stress-induced cell injury, while DLG1 overexpression produced the opposite effect. Molecular docking indicated a favorable Pue–DLG1 binding affinity. Pue significantly attenuated H2O2-induced decreases in cell viability, mitochondrial membrane potential, and increased mitochondrial reactive oxygen species (ROS). Notably, DLG1 overexpression attenuated the protective effects of Pue against oxidative damage and mitochondrial dysfunction.
Conclusions:
DLG1 plays a pro-damage role in oxidative stress-induced HLEC damage, while Pue exerts a protective effect partly through modulation of DLG1 expression. These findings suggest that DLG1 may serve as a potential target for ARC, with Pue representing a potential intervention candidate.
Oxidative stress and mitochondrial dysfunction are key contributors to age-related cataract (ARC) development. This study investigated the role of DLG1 in oxidative injury in human lens epithelial cells (HLECs) and whether puerarin (Pue) could alleviate oxidative stress and mitochondrial dysfunction.
Material and Methods:
Gene co-expression networks were constructed for differentially expressed genes (DEGs) in GSE3040 along with GSE213546. Expression, diagnostic performance, and enrichment analyses were performed on the overlapping genes in the two datasets. Functional assays were performed in hydrogen peroxide (H2O2)-induced HLECs to evaluate the role of DLG1 and Pue’s impact on oxidative stress and mitochondrial function.
Results:
DLG1, histone H4 (HIST1H4L), N alpha acetyltransferase 16 (NAA16), and Scratch family transcriptional repressor 1 (SCRT1) were consistently upregulated in ARC and exhibited high diagnostic performance. In HLECs, H2O2 increased the mRNA levels of all four genes, whereas co-treatment with Pue reversed these changes. Functionally, small interfering RNA (siRNA)-mediated DLG1 silencing mitigated oxidative stress-induced cell injury, while DLG1 overexpression produced the opposite effect. Molecular docking indicated a favorable Pue–DLG1 binding affinity. Pue significantly attenuated H2O2-induced decreases in cell viability, mitochondrial membrane potential, and increased mitochondrial reactive oxygen species (ROS). Notably, DLG1 overexpression attenuated the protective effects of Pue against oxidative damage and mitochondrial dysfunction.
Conclusions:
DLG1 plays a pro-damage role in oxidative stress-induced HLEC damage, while Pue exerts a protective effect partly through modulation of DLG1 expression. These findings suggest that DLG1 may serve as a potential target for ARC, with Pue representing a potential intervention candidate.
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