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.
Mangiferin (MGF), a bioactive compound found in mangoes and their byproducts, possesses various pharmacological activities and holds potential for use in natural nutritional supplements and pharmaceuticals. However, the low solubility and poor bioavailability significantly limit its effectiveness. To address these limitations, this study employed the natural sweetener rebaudioside A (Reb A) to encapsulate MGF within self-assembled nanomicelle (SAM), resulting in the formation of nanoscale spherical particles with an encapsulation efficiency of 87.14% ± 0.56% and a drug loading capacity of 44.31% ± 0.28%. MGF-Reb A SAM improved both the water solubility and thermal stability of MGF through structural transformation from the crystalline to the amorphous form. Additionally, MGF-Reb A SAM exhibited sustained-release properties, with 92.32% of the MGF released within 12 h. The release kinetics followed a first-order model. In Caco-2 cell studies, MGF-Reb A SAM demonstrated good cellular compatibility and increased MGF permeability across intestinal epithelial cells by enhancing passive diffusion, thereby improving bioavailability. Pharmacokinetic analysis revealed that MGF-Reb A SAM increased the bioavailability of MGF 2.41-fold. In conclusion, the Reb A-based delivery system developed in this study enhances the physicochemical properties of MGF, offering a promising strategy for its future use in food supplements and pharmaceuticals.
危险品化学品经营许可证（带存储）