Abstract: Utilizing ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry (UPLC-Q-Exactive Orbitrap-MS/MS), a total of 68 chemical constituents were identified from sea buckthorn fruit. Network pharmacology analysis and molecular docking predicted 8 potential antibacterial compounds in sea buckthorn fruit, including corilagin, epigallocatechin, and gallocatechin. These compounds might exhibit favorable binding affinities with key targets including TNF, IL6, and AKT1, potentially exerting antibacterial effects via the modulation of signaling pathways including PI3K-Akt and IL-17. Furthermore,in vitrominimum inhibitory concentration (MIC) assays confirmed the antibacterial efficacy of corilagin, epigallocatechin, gallocatechin, and taxifolin. Notably, the combination of corilagin and epigallocatechin demonstrated a synergistic inhibition againstStaphylococcus aureus, reducing MICs to 31.25 μg/mL and 62.5 μg/mL, respectively. This research, leveraging high-resolution mass spectrometry technology and integrating data from multiple databases, comprehensively characterized the chemical profile of sea buckthorn fruit, establishing a solid foundation for understanding its pharmacological properties and traditional medicinal efficacy. By integrated network pharmacology, molecular docking techniques, andin vitroexperiments, this study represented the first discovery of multiple antibacterial chemical components in sea buckthorn fruit, revealing their potential mechanisms, providing a theoretical basis for the application of sea buckthorn fruit in antibacterial and anti-infective therapies.

Key words: sea buckthorn fruit, UPLC-Q-Exactive Orbitrap-MS/MS, network pharmacology analysis, molecular docking, antibacterial active components