Revealing the therapeutic potential of Laminaria japonica polysaccharides against cataract: evidence from transcriptomics, network pharmacology, and in vivo experiments.

OBJECTIVE: To investigate the protective effects and underlying molecular mechanisms of Laminaria japonica polysaccharides (LPs) against cataract. METHODS: An integrated strategy combining transcriptomic analysis, network pharmacology, machine learning, molecular docking, and in vivo validation was employed. Differentially expressed genes were identified from the GSE213546 dataset, and key targets were screened using WGCNA, protein-protein interaction analysis, and machine learning algorithms. Molecular docking was performed to evaluate interactions between major LPs components and core targets. A UVB-induced cataract model was established in 8-week-old male Sprague-Dawley rats to validate the protective effects of laminarin by assessing lens opacity, antioxidant activity, and apoptosis-related markers. RESULTS: XDH, ANPEP, and SNCA were identified as key targets associated with cataract and LPs intervention. Major LPs components, including Laminarin, Fucoidan, and Alginate, showed stable binding affinities with these targets. In vivo experiments demonstrated that Laminarin treatment significantly reduced lens opacity, increased superoxide dismutase (SOD) activity, upregulated SMP30 and FoxO4 expression, and modulated apoptosis-related markers by decreasing Bax and cleaved Caspase-3 while increasing Bcl-2 levels. CONCLUSIONS: These findings suggest that LPs may attenuate UVB-induced cataract by targeting XDH, ANPEP, and SNCA. In vivo evidence further indicates that this intervention enhances antioxidant defenses, as reflected by increased SOD activity and upregulation of SMP30 and FoxO4, while suppressing apoptosis, thereby contributing to protection against lens damage.