The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α‐mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram‐positive bacteria, but also restore the susceptibility of colistin against Gram‐negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.
The increasing emergence and dissemination of multidrug-resistant (MDR) bacterial pathogens have intensified the need for new antibiotics and alternative therapeutic strategies. Flavonoids, a diverse group of bioactive natural compounds found in plants, have shown significant promise as antibacterial agents. Flavonoids inhibit bacterial growth through various mechanisms, including disruption of cell wall synthesis, prevention of biofilm formation, disruption of cell membrane integrity, and inhibition of bacterial efflux pumps. These actions not only reduce bacterial viability but also enhance the efficacy of conventional antibiotics, offering a potential solution to antibiotic resistance. However, challenges such as poor bioavailability limit their clinical application. Recent advances in nanotechnology-based drug delivery systems, chemical modifications, and formulation techniques have shown promise in improving flavonoid bioavailability and therapeutic efficacy. This review evaluates the antibacterial mechanisms of flavonoids, explores their potential synergistic effects with antibiotics, and highlights strategies to overcome bioavailability issues. Our findings underscore the importance of continued research on flavonoids as promising candidates for innovative antibacterial therapies aimed at combating MDR bacterial infections.
14 December 2022 in Journal of Agricultural and Food Chemistry
In 2022, human breast cancer (HBC) and canine mammary tumors (CMTs) remained the most prevalent malignant tumors worldwide, with high recurrence and lethality rates, posing a significant threat to human and dog health. The development of breast cancer involves multiple signaling pathways, highlighting the need for effective inhibitory drugs that target key proteins in these pathways. This article reviews the dysregulation of the EGFR, PI3K/AKT/mTOR, Hippo, pyroptosis, and PD-1/PD-L1 signaling pathways in HBC and CMT, as well as the corresponding drugs used to inhibit tumor growth, with the aim of providing theoretical support for the development of more efficient drugs.