OBJECTIVE  To investigate the potential mechanism of action of schizandrin C(SC) against atherosclerosis(AS) in vitro.

METHODS  Based on network pharmacology, the potential active components and targets of SC for treating AS were predicted, a protein-protein interaction network was constructed, and GO and KEGG enrichment analyses of the targets were performed using the DAVID database. An in vitro model was established using oxidized low-density lipoprotein(ox-LDL). HUVECs were randomly divided into 6 groups: control group(routine culture), model group(ox-LDL), SC low-dose group(ox-LDL + 1 μmol·L⁻¹ SC), SC medium-dose group(ox-LDL + 5 μmol·L⁻¹ SC), SC high-dose group(ox-LDL + 25 μmol·L⁻¹ SC), and atorvastatin group(ox-LDL + 1 μmol·L⁻¹ AT). Cytotoxicity was assessed by the CCK-8 assay. NO release was measured using NO assay kit. The levels of IL-6 and TNF-α were determined by ELISA. The expression of apoptosis-related proteins was analyzed by Western blotting and immunofluorescence. The apoptotic rate was evaluated by flow cytometry. Finally, the relevant signaling pathways predicted by network pharmacology were experimentally validated.

RESULTS Seventy-eight potential targets of SC for the treatment of atherosclerosis(AS) were identified, among which ErbB2, AKT1, and MTOR were recognized as core targets. KEGG pathway enrichment analysis revealed that these targets were primarily enriched in the ErbB, PI3K-AKT and other signaling pathways. The CCK-8 assay indicated that SC at concentrations ≤25 μmol·L⁻¹ was suitable for subsequent cellular experiments. Compared with the control group, the model group exhibited significantly elevated levels of NO, IL-6, TNF-α, apoptosis rate, and protein expression of Cleaved Caspase-3, Cleaved Caspase-9 and Bax, while the expression of Bcl-2 and p-ErbB2 was markedly reduced. In contrast, both SC and atorvastatin significantly attenuated the increases in the levels of NO, IL-6, TNF-α, apoptosis rate, and Cleaved Caspase-3, Cleaved Caspase-9 and Bax expression induced by ox-LDL, and concurrently increased the expression of Bcl-2 and p-ErbB2.

CONCLUSION SC may protect against ox-LDL-induced vascular endothelial cell injury by inhibiting apoptosis, thereby exerting therapeutic effect on AS.