Pharmacological potential of Clinacanthus nutans: integrating network pharmacology with experimental studies against lung cancer

Abstract

Limited treatment options and emerging resistance necessitate the exploration of novel lung cancer therapeutics. This study investigates the potential of Dandang Gendis (Clinacanthus nutans) leaf extract, a Southeast Asian plant, using a combined in vitro and in silico approach. The in vitro study assessed the extract’s cytotoxicity towards A549 lung cancer and TIG-1 fibroblast cells using the WST-1 assay. The in silico analysis identified active compounds, predicted a target protein, performed functional annotation and explored mechanisms through molecular docking and dynamics simulations. The in vitro analysis revealed a significantly higher flavonoid content (177.63 mg QE/g) compared to phenols (45.66 mg GAE/g), suggesting a potential role for flavonoids. Importantly, the extract displayed remarkable selectivity in its cytotoxic effects. It significantly reduced A549 lung cancer cell viability while maintaining high viability in normal TIG-1 fibroblasts, particularly at the 24-hour exposure. While concentrations above 200 μg/ mL significantly decreased the viability of A549 cancer cells, normal TIG-1 fibroblast cells maintained high viability (>50%) at these concentrations. In silico analysis identified isomollupentin 7-O-β-glucoside, isoorientin, and isovitexin, all C-glycosyl flavones, as potential active compounds. These compounds were predicted to act as PD-L1 inhibitors, potentially enhancing T cell-mediated antitumor activity. This aligns with the observed selective cytotoxicity. Overall, this study provides evidence for the potential of the C. nutans extract and its C-glycosyl flavone constituents, particularly the identified compounds, as novel lung cancer therapeutics targeting the PD-L1 pathway for T cell-mediated tumor suppression.

GRAPHICAL ABSTRACT

Keywords:

• A549
• Anti-cancer
• Clinacanthus nutans
• Network pharmacology
• PD-L1