Qingre Baidu mixture-induced effect of AI-2 on Staphylococcus aureus and Pseudomonas aeruginosa biofilms in chronic and refractory wounds

The present study aimed to investigate the effect of the traditional Chinese medicine Qingre Baidu mixture (QBM) on the regulation of various parameters, including the morphology of bacterial biofilms, the bacterial density sensing system, the self-induction of the molecule autoinducer (AI)-2 and the hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF) signaling pathway. For that purpose, Sprague Dawley rats were administered the QBM, the Wu Wei Xiao Du Wan drink (WXD) and cefoperazone (Cef) prior to drug isolation from serum. Vibrio harveyi BB170 was employed as a reporter strain to detect the AI-2 signaling pathway in Staphylococcus aureus and Pseudomonas aeruginosa. The expression of HIF-1 and VEGF expression was examined by immunohistochemistry. ELISAs were used to measure the expression of HIF-1, HIF-2, HIF-3 and VEGF. The level of inflammation was evaluated by hematoxylin and eosin staining. Biofilm formation and the number of macrophages were detected by immunofluorescence. The results revealed that the QBM could reduce the concentration of AI-2 derived from Staphylococcus aureus and Pseudomonas aeruginosa, and markedly increase the levels of HIF-1, HIF-2 and VEGF in chronic and refractory wounds. The QBM strongly inhibited the formation of bacterial biofilms and the number of macrophages, therefore promoting wound healing. In conclusion, the QBM could inhibit the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa through decreasing the levels of AI-2 while upregulating the expression of HIF-1, HIF-2 and HIF-3, which increased the levels of VEGF, thereby promoting angiogenesis and wound healing in chronic and refractory wounds.