Context: Naoxintong capsule (NXT) is one of the most prevalent Traditional Chinese Medicine formulations in the treatment of coronary heart disease (CHD), yet the action of pharmacodynamic components remains unclear.
Objective: To determine the basis by which pharmacodynamic components of NXT may be effective in the treatment of CHD.
Materials and methods: The protective effect of NXT (0.01-100 μg/mL) on 293 T and hy926 cells was determined by MTT assay for 24 h. Afterwards, to investigate the pharmacodynamic material basis of NXT in anti-inflammatory and antioxidant effects, based on previous UPLC/Q-TOF analysis, 293 T and hy926 cells were divided into control (treated with solvent), model (incubated with TNF-α, LPS or H2O2), intervention (treated with UPLC components) and positive groups. After 24 h of treatment, all cells were tested to verify the screening results. MOE software was applied to dock bioactive compounds with phosphoinositide 3-kinase (PI3K), then the protein expression and phosphate levels were determined by western blotting.
Results: NXT could significantly inhibit the expression of NF-κB, MMP-9 and NO in cells with IC50 values of 0.1178, 0.1182 and 0.1094 μg/mL. Based on the screening results, six components of NXT were identified (calycosin, ferulic acid, salvianolic acid B, ononin, salvianolic acid E, and salvianolic acid F) which can inhibit NF-κB, MMP-9, and NO simultaneously, while exerting cytoprotective effects by inhibiting the activation of the PI3K/AKT pathway under different conditions by virtue of their advantageous interaction with PI3K.
Conclusions: These ingredients have outstanding therapeutic potential and may provide a scientific basis for the future application and research of NXT.
Keywords: High-throughput screening; PI3K/AKT pathway; biological activity ingredients.