Combination of Aloe Emodin, Emodin, and Rhein from Aloe with EDTA Sensitizes the Resistant to Polymyxins

Background: The continuous emergence and spread of polymyxin-resistant pose a significant global health challenge, necessitating the development of novel therapeutic strategies. Aloe, with its long-standing history of medicinal use, has recently been the subject of substantial research for its efficacy against pathogenic infections.

Methods: This study investigates the potential application of anthraquinone components in aloe against polymyxin-resistant by liquid chromatography-mass spectrometry, in vitro activity assessment, and construction of animal infection models.

Results: The findings demonstrate that aloe emodin, emodin, rhein, and their mixtures in equal mass ratios (EAR) exhibit strain-specific antibacterial activities against polymyxin-resistant . Co-administration of EAR with EDTA synergistically and universally enhanced the antibacterial activity and bactericidal efficacy of polymyxins against polymyxin-resistant , while also reducing the frequency of polymyxin-resistant mutations in polymyxinssensitive . Following toxicity assessment on human hepatic and renal cell lines, the combination therapy was applied to skin wounds in mice infected with polymyxin-resistant . Compared to monotherapy, the combination therapy significantly accelerated wound healing and reduced bacterial burden.

Conclusions: The combination of EAR and EDTA with polymyxins offers a novel therapeutic approach for managing skin infections caused by polymyxinresistant .