越南植物天鵝絨羅望子應用生物活性分子網絡標的探索有效成分之研究

Managing inflammation and oxidative stress is a key therapeutic strategy for dry eye disease (DED) treatment. In Vietnam, Dialium cochinchinense leaves are widely used to treat malaria, infections and inflammation diseases. In this study, D. cochinchinense leaf extracts demonstrated significant anti-inflammatory effects by preventing IκBα degradation within the nuclear transcription factor-κB pathway in LPS-activated macrophages. Furthermore, these extracts exhibited antioxidant and cytoprotective properties in bovine corneal epithelial cells against benzalkonium chloride-induced reactive oxygen species generation and cell death. A bioactive molecular networking approach was applied to identify key bioactive components responsible for these effects. In the obtained network, nodes with high bioactivity scores (r > 0.75, p < 0.05) were prioritized for isolation. This led to the identification of one undescribed compound, identified as 6S,9R-2′-O-sinapoyl-roseoside (compound 1), along with 11 known phenolic compounds (compounds 2–12). Subsequent bioactivity validation revealed that 10 of the 12 isolates exhibited significant cell-protective effects, highlighting the efficiency of bioactive molecular networking in prioritizing rapid and targeted isolation. Among these, compounds 1–3 showed the most pronounced protective activity. Network pharmacology analysis identified 65 common targets between the isolated compounds 1–3 and DED. The core targets, including AKT1, PIK3CA, EGFR, CASP3, MTOR, CCND1, BRAF, and IGF1R, are related to the PI3K/AKT, MAPK, and cancer-related pathways involved in inflammation, apoptosis, angiogenesis, and cell proliferation. Molecular docking studies demonstrated strong interactions between compounds 1–3 and these targets, with binding energies ranged from –9.099 to –4.869 kcal/mol. Molecular dynamic simulations showed minimal fluctuations, suggesting strong and stable binding between bioactive compounds and core proteins. These results suggest the potential of D. cochinchinense leaf extracts and their isolated compounds as promising therapeutic agents for DED.