Abstract:

Honokiol (HNK), an isomer of magnolol, is an effective antibacterial and anti-inflammatory component within Magnolia officinalis. In order to enhance the antimicrobial effect of Honokiol against methicillin resistant Staphylococcus aureus (MRSA), in this study, MOF material (HKUST-1) was synthesized from Cupric Acetate Monohydrate and Trimesic acid at room temperature, and HNK/HKUST-1 was prepared as HNK-loaded nanoparticles. The in vitro drug release test was used to assess the drug release performance in different media. FIC test was conducted to verify the effect of HKUST-1 in conjunction with HNK on the antibacterial efficacy of HNK. The minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), inhibition rate, cell membrane damage and reactive oxygen species (ROS) production of the antimicrobial agents against MRSA were evaluated. The results demonstrated that the nanoparticles exhibited a typical multi-faceted crystal structure, with a particle size of 496.93 nm±7.01 nm. Drug loading was 18.88%±0.11%. The drug release ability of HNK/HKUST-1 in acidic medium was significantly better than that in neutral medium. The combination of HKSUT-1 and HNK had an addition effect on FIC (5/8) of MRSA. The bactericidal effect of HNK/HKUST-1 nanoparticles on MRSA was superior to that of HNK, and the antibacterial effect of HNK/HKUST-1 nanoparticles was more enduring. A notable leakage of intracellular components, including β-galactosidase, proteins, and DNA, was observed in MRSA following treatment with HNK/HKUST-1. Additionally, a notable increase in intracellular reactive oxygen species concentration was evident, indicating that the nanoparticles could exert an antibacterial effect by disrupting the cell membrane integrity and stimulating the generation of intracellular reactive oxygen species. These effects were more pronounced than those observed with HNK alone. In conclusion, the encapsulation of HNK using HKUST-1 markedly enhanced the antimicrobial effect of HNK against MRSA. Furthermore, the nanoparticles have the potential for drug release in an acidic environment at the site of bacterial infection, which is anticipated to enhance the efficacy of HNK in clinical applications.

Key words: honokiol, metal-organic framework (MOF), HKUST-1, MRSA, antibacterial