Researchers have developed a novel approach to combating the growing threat of antibiotic resistance by harnessing the power of nanoparticles and a natural antimicrobial compound. In their study, they synthesized zinc oxide nanoparticles (ZnONPs) using extracts from the Loranthus cordifolius plant and then coated them with the natural compound anethole, derived from anise oil.
The researchers found that these anethole-loaded ZnONPs demonstrated superior antibacterial activity against a range of pathogenic bacteria, including both Gram-negative and Gram-positive species. Notably, the anethole-coated ZnONPs were more effective than commercially available ZnONPs and even outperformed the green-synthesized ZnONPs alone. The researchers also discovered that the anethole-loaded ZnONPs were potent inhibitors of the bacterial enzyme DNA gyrase, which is crucial for DNA replication and a common target for antibiotics.
This innovative approach combining green-synthesized nanoparticles and a natural antimicrobial compound holds great promise for developing new strategies to combat the growing problem of antibiotic resistance, which is a major global health concern.
Combating Antibiotic Resistance with Nanoparticles and Natural Compounds
The increasing prevalence of antibiotic-resistant bacteria, often referred to as “superbugs,” is a pressing global health issue. As more and more bacteria develop resistance to commonly used antibiotics, the effectiveness of these life-saving drugs is diminishing, making it increasingly challenging to treat infectious diseases. In response to this growing threat, researchers have been exploring alternative approaches, including the use of nanoparticles and natural antimicrobial compounds.
Green Synthesis of Zinc Oxide Nanoparticles
In this study, the researchers focused on the synthesis of zinc oxide nanoparticles (ZnONPs) using a green, eco-friendly approach. Instead of relying on traditional chemical methods that often involve hazardous reagents and generate toxic waste, the team utilized extracts from the Loranthus cordifolius plant as a natural reducing and capping agent. This green synthesis process not only produces nanoparticles in a sustainable manner but also imparts unique properties to the ZnONPs, enhancing their antimicrobial potential.

Coating ZnONPs with Anethole
The researchers then took the green-synthesized ZnONPs and coated them with the natural compound anethole, which is derived from anise oil. Anethole is known for its antimicrobial and anti-inflammatory properties, making it a promising candidate for enhancing the effectiveness of the ZnONPs.
The coating process involved a nanoprecipitation technique, where the ZnONPs were dissolved in ethanol and the anethole was dissolved in acetone. This solution was then injected into water, causing the nanoparticles to precipitate and form a stable coating of anethole on the ZnONP surface.

Fig. 2
Characterizing the Anethole-Loaded ZnONPs
The researchers used a variety of analytical techniques to confirm the successful synthesis and coating of the ZnONPs. Ultraviolet-visible (UV-Vis) spectroscopy revealed distinct absorption peaks for the green-synthesized ZnONPs and the anethole-coated ZnONPs, indicating the incorporation of the anethole.
Transmission electron microscopy (TEM) analysis showed that the green-synthesized ZnONPs had a quasi-spherical shape with an average size of around 14.5 nanometers. The anethole-coated ZnONPs maintained a similar spherical morphology, with an average size of approximately 14.8 nanometers.
Furthermore, Fourier-transform infrared (FTIR) spectroscopy confirmed the presence of both ZnO and anethole signatures in the coated nanoparticles, demonstrating the successful surface modification.

Fig. 3
Enhanced Antibacterial Efficacy of Anethole-Loaded ZnONPs
The researchers evaluated the antibacterial activity of the green-synthesized ZnONPs, the commercially available ZnONPs, and the anethole-loaded ZnONPs against a panel of pathogenic bacteria, including both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Bacillus subtilis and Staphylococcus aureus) species.
The results were quite remarkable. The anethole-loaded ZnONPs demonstrated the greatest antibacterial efficacy, outperforming both the green-synthesized ZnONPs and the commercially available counterparts. This enhanced activity was evident in the larger zones of inhibition, lower minimum inhibitory concentrations (MICs), and lower minimum bactericidal concentrations (MBCs) observed for the anethole-coated ZnONPs.

Fig. 4
Inhibition of DNA Gyrase: A Crucial Antibacterial Mechanism
The researchers also investigated the ability of the different ZnONP formulations to inhibit the activity of the bacterial enzyme DNA gyrase, which plays a crucial role in DNA replication and is a common target for many antibiotics.
Interestingly, the anethole-coated ZnONPs exhibited the most potent inhibition of DNA gyrase, with an IC50 (half-maximal inhibitory concentration) value of 0.78 micromolar. This finding suggests that the combination of ZnONPs and the natural compound anethole can effectively disrupt the essential DNA replication process in bacteria, contributing to their enhanced antibacterial properties.
Potential Applications and Future Directions
The development of anethole-loaded ZnONPs represents a promising approach for addressing the growing challenge of antibiotic resistance. The green synthesis method, the use of a natural antimicrobial compound, and the demonstrated superior antibacterial efficacy make this technology an attractive candidate for various biomedical applications, such as wound healing, skin care, and the development of novel antimicrobial agents.
Moreover, the researchers suggest that the combination of ZnONPs and anethole may have broader implications beyond just antibacterial applications. The unique properties of this nanocomposite could be explored for potential synergistic effects in treating viral infections or even certain types of cancer, leveraging the targeted delivery and enhanced cellular uptake capabilities of nanoparticles.
As the scientific community continues to grapple with the urgent need for new antimicrobial strategies, this innovative approach combining green-synthesized nanoparticles and natural compounds offers a promising avenue for future research and development. By harnessing the power of nanoscale materials and natural bioactive agents, the researchers have demonstrated a novel way to combat the growing threat of antibiotic resistance and pave the way for more effective and sustainable solutions in the field of infectious disease management.
Author credit: This article is based on research by Muhammad Waqas Mazhar, Muhammad Ishtiaq, Mehwish Maqbool, Anila Arshad, Mohammed Ali Alshehri, Seham Sater Alhelaify, Ohud Muslat Alharthy, Mustafa Shukry, Samy M. Sayed.
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