Investigating the therapeutic potential of Ganoderma lucidum in treating optic nerve atrophy through network pharmacology and experimental validation.

OBJECTIVE

The aim of this study is to employ network pharmacology to identify potential therapeutic targets for Ganoderma lucidum in the treatment of optic atrophy, and elucidate the underlying pharmacological mechanism.

METHODS

This study is mainly divided into two parts. In the first part, the chemical composition and Target of Ganoderma lucidum compound were predicted by TCMSP and Swiss Target Prediction, and the crossover gene between OA and Ganoderma lucidum target gene was screened based on GeneCards and OMIM database. Then, the target genes were enriched and the main pathways of action were analyzed to discover the possible mechanism of action for the treatment of optic atrophy. Finally, the selected core compounds and core targets were interfaced to understand the main binding patterns and affinity. The second part mainly verifies whether Ganoderma lucidum polysaccharide has protective effect on RGC. Firstly, CCK8 method was used to detect the proliferation and virulence analysis of RGC-5 cells with different concentrations of Ganoderma lucidum polysaccharide, and then RGC-5 cells were cultured in subgroups for 12 h, and then put into anaerobic encapsulation to make molds. After 24 h of continuous culture, cells were removed and collected for subsequent RT-PCR and WB detection.

RESULTS

Through screening target genes of Ganoderma lucidum and OA, 85 potential therapeutic targets were obtained by intersection. Through PPI network analysis of 85 potential targets, it was found that the degree values of TP53, TNF, CASP3, IL6, EGFR, MTOR, ESR1 and other targets were higher. (+)-Ganoderic acid Mf, (+)-Methyl ganolucidate A, epoxyganoderiol A, Ergosta-4,7, 22-Trien-3, 6-Dione and other compounds play a key role in the whole network. It may be the key compound of ganoderma lucidum in treating OA. Through enrichment pathway analysis, it was found that the number of genes was enriched in AGE-RAGE signaling pathway, cAMP signaling pathway, inflammation and cancer pathways, and the structure of TP53, TNF, CASP3, and IL6 binding to the above compounds was stable and the binding activity was high.

CONCLUSIONS

The findings suggest that Ganoderma lucidum may exert its therapeutic effects on optic atrophy by targeting TP53, TNF, CASP3, and IL6. Additionally, it may also be involved in the AGE-RAGE signaling pathway and cAMP signaling pathway. These results provide reference for the clinical application of ganoderma lucidum in the treatment of OA.