Qiguiyin Decoction Improves Multidrug-Resistant Pseudomonas aeruginosa Infection in Rats by Regulating Inflammatory Cytokines and the TLR4/MyD88/NF-κB Signaling Pathway

Abstract

Pseudomonas aeruginosa (PA), a Gram-negative bacterium, has a high detection rate in hospital-acquired infections. Recently, the frequent appearance of multidrug-resistant (MDR) PA strain with high morbidity and mortality rates has aggravated the difficulty in treating infectious diseases. Due to its multiple resistance mechanisms, the commonly used antibiotics have gradually become less effective. Qiguiyin decoction (QGYD) is a clinically experienced prescription of Chinese herbal medicine, and its combined application with antibiotics has been confirmed to be effective in the clinical treatment of MDR PA infection, which could be a promising strategy for the treatment of drug-resistant bacterial infections. However, the mechanism of QGYD restoring antibiotics susceptibility to MDR PA remains unclear. In the present study, we investigated the effects of QGYD and levofloxacin (LEV) singly or in combination on MDR PA-induced pneumonia rat models. Further analysis was carried out in the serum differential expression profiles of inflammatory cytokines by cytokine antibody array. Besides, the lung TLR4/MyD88/NF-κB signaling pathway was detected by RT-qPCR. Our results showed that based on the treatment of MDR PA-infected rat model with LEV, the combination of QGYD improved the general state and immune organ index. Furthermore, it moderately increased the expressions of proinflammatory cytokines including IL-1β, IL-6, and TNF-α in the early stage of infection and decreased their release rapidly in the later stage, while regulated the same phase change of anti-inflammatory cytokine IL-10. In addition, the adhesion molecule ICAM-1 was significantly downregulated after QGYD combined with LEV treatment. Moreover, the mRNA expressions of TLR4, MyD88, NF-κB, and ICAM-1 were significantly downregulated. These results indicated that the mechanism of QGYD restoring LEV susceptibility to MDR PA was related to its regulation of inflammatory cytokines and the TLR4/MyD88/NF-κB signaling pathway, which provides theoretical support for the clinical application of QGYD combined with LEV therapy to MDR PA infection.

Sodium houttuyfonate effectively treats acute pulmonary infection of Pseudomonas aeruginosa by affecting immunity and intestinal flora in mice

“…Similar results were found in our study, where multiple inflammatory cytokines in P. aeruginosainduced pneumonia mice produced significant differences after SH treatment, that is, SH intervention reduced the release of each of these pro-inflammatory cytokines. Moderate inflammation is beneficial and protective, while both excessive and insufficient inflammation is detrimental to the body (Chen et al, 2022).…”

“…Similar results were found in our study, where multiple inflammatory cytokines in P. aeruginosa -induced pneumonia mice produced significant differences after SH treatment, that is, SH intervention reduced the release of each of these pro-inflammatory cytokines. Moderate inflammation is beneficial and protective, while both excessive and insufficient inflammation is detrimental to the body ( Chen et al., 2022 ). Compared to the model group, SH reduces the inflammatory response in the body and maintains it at an appropriate level, which may ensure that the body is functioning properly in draining pathogenic bacteria and toxins, controlling the inflammatory response, and avoiding the waterfall effect and severe self-injury.…”

Mechanism of Qiguiyin Decoction Treats Pulmonary Infection Caused by Pseudomonas aeruginosa Based on Gut Microbiota and Metabolomics

“…Previous studies exhibited that QGYD have the function of delay and reverse PA resistance to antibiotics, modulate inflammation and immune disorders, and enhance clinical curative effect against PA infection. 8 , 9 However, the pharmacodynamic mechanism of QGYD on CRPA infection remains unclear.…”