Full
Outline
To investigate the potential therapeutic targets and underlying molecular mechanisms of Z-ligustilide (Z-LIG) in treating retinitis pigmentosa (RP).
By integrating multiple databases, such as GeneCards and TargetNet, common targets for RP and Z-LIG were identified. Protein-protein interaction (PPI) network analysis of the targets was conducted using the STRING database and analyzed in Cytoscape to identify core targets. The DAVID database was employed for the functional enrichment analysis of Gene Ontology (GO) and the pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) for the core targets. The PubChem database was accessed for molecular docking verification to validate the binding affinity between Z-LIG and the core targets. Finally, male rd10 mice were randomly divided into a control group (n=5) and a Z-LIG treatment group (n=5). The protective effect of Z-LIG on the visual function in rd10 mice was verified through visual electrophysiology and behavioral tests. Western blotting and RT-qPCR were utilized to investigate the molecular mechanism of action.
A total of 66 shared targets between RP and Z-LIG were identified through the screening process. PPI network analysis identified 55 key targets. GO enrichment analysis yielded 623 terms, which covering 3 dimensions, including cellular component (CC), molecular function (MF), and biological process (BP), such as inflammatory response. KEGG pathway enrichment analysis further concentrated 124 terms, which were enriched in the PI3K-Akt signaling pathway. Molecular docking suggested that Z-LIG could specifically bind with high affinity to RP-related core targets (such as EGFR and STAT3) via hydrogen bonds. In animal experiments, compared to the control group, the rd10 mice from the Z-LIG group showed a greater preference for the dark environment in the light/dark transition test (P<0.05), exhibited significantly higher amplitudes of A-wave and B-wave in electroretinogram (ERG) (P<0.05), greater number of outer nuclear layers, with fewer apoptotic cells and less microglial activation (P<0.05), demonstrated obviously reduced protein levels of p-PI3K/PI3K and p-AKT/AKT in the retina (P<0.05), and had notably down-regulated mRNA levels of pro-inflammatory cytokines IL-1β and IL-6 (P<0.05).
Z-LIG may exert a protective effect on the retina of rd10 mice by inhibiting the activation of the PI3K/AKT-inflammatory axis, thereby delaying retinal degeneration.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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