Exploring the Active Components and Mechanisms of Schisandra Chinensis for Treatment of Non-small Cell Lung Cancer Based on Network Pharmacology and Experimental Validation.

INTRODUCTION Schisandra chinensis has been reported to exhibit antitumor activity; however, its active components and molecular mechanisms in non-small cell lung cancer (NSCLC) remain unclear.

METHODS Network pharmacology was employed to identify active compounds and potential targets of Schisandra chinensis against NSCLC, followed by protein-protein interaction analysis, GO and KEGG enrichment analyses, and molecular docking. A549 cells were used for experimental validation. Cell viability was assessed by MTT assay, oxidative stress markers (GSH, SOD, MDA) were quantified, and the expression of PTGS2, inflammatory factors, and apoptosis-related genes was examined by qRT-PCR and Western blot.

RESULTS Eight active components of Schisandra chinensis were identified, with seven overlapping targets related to NSCLC. Molecular docking revealed that Gomisin R exhibited the strongest binding affinity to PTGS2, with a docking score of -7.3 kcal/mol. In vitro experiments demonstrated that Gomisin R significantly inhibited A549 cell proliferation in a dose- and time-dependent manner, with a pronounced effect observed at 25 µM (p < 0.01). Gomisin R markedly downregulated PTGS2 expression at both mRNA and protein levels (p < 0.001), accompanied by reduced expression of inflammatory cytokines IL-1β and IL-6, increased antioxidant capacity (elevated GSH and SOD levels and decreased MDA content), and modulation of apoptosis-related genes, characterized by decreased Bcl-2 and increased Caspase 9 expression (p < 0.05-0.001). These effects were partially reversed by the PTGS2 agonist rebamipide.

DISCUSSION These findings suggest that Gomisin R may modulate PTGS2-associated inflammatory and redox pathways in NSCLC cells. The integration of network pharmacology with experimental validation provides a mechanistic framework for understanding the potential role of Gomisin R in NSCLC-related research, although further in vivo studies are required to confirm its translational relevance.

CONCLUSION Gomisin R exerts anti-NSCLC effects, in part, by regulating PTGS2 expression, leading to suppression of cell proliferation, attenuation of oxidative stress and inflammatory responses, and induction of apoptosis in A549 cells. This study provides quantitative evidence supporting Gomisin R as a key active component of Schisandra chinensis for the treatment of NSCLC.