Sustainable MnO2/MgO Bimetallic Nanoparticles Capped with Sword Fern Methanol Extract Attain Antioxidant/Anti-Biofilm Potential: A UPLC-ESI/LC/MS and Network Pharmacology-Supported Study

<b>Background</b>: <i>Nephrolepis exaltata</i> (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of <i>Nephrolepis exaltata</i> leaf methanol extract (NEME-MnO₂-MgO BNPs). <b>Methods</b>: The NEME was subjected to UPLC/MS analysis, followed by characterization of its NPs by size, zeta potential, FTIR, entrapment efficiency, and release. Then, antioxidant, antimicrobial and antibiofilm assays were employed, followed by in silico studies. <b>Results</b>: The UPLC/MS analysis of NEME led to the tentative identification of 27 metabolites, mostly phenolics. The MnO₂-MgO BNPs presented a uniform size and distribution and exhibited IC₅₀ values of 350 and 215.6 μg/mL, in the DPPH and ABTS assays, respectively. Moreover, the NPs exhibited antimicrobial and anti-biofilm efficacies against <i>Pseudomonas aeruginosa</i>, <i>Klebsiella pneumonia</i> (ATCC-9633), <i>Staphylococcus aureus</i> (ATCC-6538), <i>Escherichia coli</i>, <i>Bacillus cereus</i>, and <i>C. albicans</i>, with MIC values of 250-500 μg/mL. The MnO₂-MgO BNPs inhibited <i>Candida albicans</i> biofilms with a % inhibition of 66.83 ± 2.45% at 1/2 MIC. The network pharmacology highlighted epigallocatechin and hyperoside to be the major compounds responsible for the anti-biofilm potential. The ASKCOS facilitated the prediction of the redox transformations that occurred in the green synthesis, while the docking analysis revealed enhanced binding affinities of the oxidized forms of both compounds towards the outer membrane porin OprD of <i>P. aeruginosa</i>, with binding scores of -4.6547 and -5.7701 kcal/mol., respectively. <b>Conclusions</b>: The greenly synthesized <i>Nephrolepis exaltata</i> bimetallic nanoparticles may provide a promising, eco-friendly, and sustainable source for antimicrobial agents of natural origin with potential biofilm inhibition.