Phytochemical profiling and multi-target antibacterial in silico potential of Algerian wild sea buckthorn leaves.

This study investigates the phytochemical profile and mechanistic bioactivity of sea buckthorn (Hippophae rhamnoides L.) leaves harvested from wild Algerian species. The research integrates quantitative HPLC profiling with in vitro and in silico assays to elucidate the molecular basis of its biological potential, specifically targeting the transpeptidase domain of Penicillin-Binding Protein 3. Two extracts (pure ethanol and 50:50 hydroethanol) were evaluated for their total phenolic, flavonoid, and tannin contents, along with antioxidant and antimicrobial activities. Key bioactive compounds identified through HPLC were subjected to Molecular Docking, Density Functional Theory, and 100 ns Molecular Dynamics (MD) simulations to assess their interactions with Penicillin-Binding Protein 3, as the primary target for molecular dynamics, while FtsZ and DNA Gyrase B were evaluated to assess multi-targeting potential. The hydroethanolic extract exhibited a higher yield (10.9%) compared to the ethanolic extract (3.7%), as well as superior levels of total phenolics (207.07 ± 0.94 mg GAE/g DW), flavonoids (4.19 ± 0.21 mg CE/g DW), and tannins (191.76 ± 1.55 mg CE/g DW). While the ethanolic extract showed higher antioxidant activity (IC