Phenolic compounds from Nicotiana tabacum inflorescence: optimized extraction, chemical composition, evaluation of antioxidant activity integrating network pharmacology and molecular docking analysis

Tobacco (Nicotiana tabacum) inflorescence, an agricultural by-product that remains underutilized, is an excellent source of bioactive components but has received limited research interest. This study developed an ultrasound-assisted extraction (UAE) process to optimize the recovery of phenolic compounds (PCs) from this material. The phenolic profiles and antioxidant capacities were systematically evaluated across five cultivars (YY87, ZY100, K326, HD, and CB1). The optimal UAE conditions were determined as follows: ultrasound power of 335 W, liquid-solid ratio of 51 mL/g, ethanol concentration of 45%, and extraction time of 31 min, yielding a PC content of 24.33 ± 0.54 mg GAE/g DW. The model’s reliability was confirmed by the close match between the predicted and experimental values. Considerable variations in PC content, individual phenolic compounds, and antioxidant activities were found among cultivars, with K326 and HD showing the highest levels. Rutin, chlorogenic acid, and neochlorogenic acid were strongly associated with ABTS, DPPH, and hydroxyl radical scavenging activities, as well as reducing power. Network pharmacology analysis revealed that nine PCs targeted 71 oxidative stress-associated genes. Protein-protein interaction (PPI) network analysis identified AKT1 and TNF as central hub targets. Molecular docking confirmed stable binding interactions between these key PCs and the targets, with binding energies ≤ − 7.0 kcal/mol. These findings provide a comprehensive experimental basis for the utilization of tobacco inflorescence PCs as a prospective source of antioxidants.