Multifaceted Therapeutic Potential of <i>Parthenium hysterophorus</i> L.: Phytochemical Profiling, Toxicity, Biofilm Inhibition, and Antidiabetic Activity

Chronic diabetes, often linked to oxidative stress and microbial infections, requires safer, multifunctional therapies. Parthenium hysterophorus L., a member of the Asteraceae family, has long been used in traditional medicine for its therapeutic properties. This study explores its potential in managing diabetes and related complications. Chemical analysis revealed hydroxyl-rich compounds, such as phenols and phenolic acids, with a prominent Fourier transform infrared (FTIR) band at 3378.8 cm^-1. The ethyl acetate fraction (EAF) and AQF fractions exhibited significant antioxidant activity (IC₅₀: 14.71 ± 0.64 and 33.4 ± 0.89 µg/mL) and significant antibacterial effects against Staphylococcus aureus and Pseudomonas aeruginosa (minimum inhibitory concentration: 312.5 µg/mL). Notably, the EAF fraction showed anti-biofilm activity (IC₅₀: 3110 ± 0.10 µg/mL) and potent α-glucosidase inhibition (IC₅₀: 0.112 ± 0.006 µg/mL). Molecular docking revealed that ferulic acid exhibited the highest binding affinity for the 3TOP transcriptional regulator's active site (-6.309 kcal/mol), while vanillic acid interacted robustly with the 2UV0 and 4F5S enzymes (docking scores: -6.299 and -6.161 kcal/mol). Cluster analysis confirmed stable binding clusters, particularly for ferulic acid. MD simulations revealed minimal RMSD fluctuations and favorable solvent accessible surface area (SASA) values, indicating stable complex formation and significant interaction stability. Ferulic acid showed the most favorable binding with the 3TOP enzyme, reinforced by hydrophobic and hydrogen bonding interactions. In case of pure compounds tested, ferulic acid demonstrated significant biofilm (IC₅₀: 3.25 ± 0.54 µg/mL) as well as α-glucosidase inhibition (IC₅₀: 0.067 ± 0.0013 µg/mL). Cytotoxicity assays on HEK293 (human embryonic kidney cells) showed no significant viability reduction at 2.5% concentration, but a 74% reduction at 10%, indicating dose-dependent cytotoxicity. These findings suggest P. hysterophorus L. as a promising natural source for multifunctional therapies targeting oxidative stress, infections, and hyperglycemia, with ferulic acid as a potent bioactive compound. Further studies on pharmacokinetics and pharmacodynamics are warranted to evaluate its therapeutic potential.