ABSTRACT
Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.
Subject(s)
Anti-Bacterial Agents/pharmacology , Berberine/pharmacology , Ciprofloxacin/pharmacology , Klebsiella pneumoniae/drug effects , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Multiple, Bacterial , Drug Synergism , Inhibitory Concentration 50 , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/genetics , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Microbial Sensitivity TestsABSTRACT
Curcumin is a natural polyphenol with powerful antioxidant and anti-inflammatory properties. The present study evaluated the protective effect of curcumin on myocardial injury in rats as well as the mechanisms underlying these effects, and examined the expression of nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ) and B-cell leukemia/lymphoma-2 (Bcl-2) following myocardial infarction. A rat model of myocardial infarction was successfully established. Hematoxylin and eosin staining showed cellular atrophy and hyperchromatic cytoplasm in the myocardial infarction area. The myocardial cells displayed lysis and breakage of cardiac muscle fibers, karyopyknosis and karyorrhexis associated with infiltration of inflammatory cells and proliferation of fibrous tissue. Curcumin treatment at a dosage of 150 mg/kg/body weight resulted in an increase in surviving cells, fewer apoptotic cells, decreased proliferation of fibrous tissue and reduced infiltration of inflammatory cells, though necrosis was still present compared with the rats without curcumin treatment. The immunohistochemical assay demonstrated that curcumin treatment inhibited the expression of NF-κB, but increased the expression of PPAR-γ. The results of the reverse transcription-polymerase chain reaction indicated that curcumin treatment significantly increased the mRNA expression levels of Bcl-2 (P<0.01). Therefore, curcumin antagonizes cardiomyocyte apoptosis and inhibits inflammatory cell infiltration following myocardial infarction, which may be associated with its inhibitory effects on the expression of NF-κB, and activating effects on the expression of PPAR-γ and Bcl-2 in myocardial cells. Curcumin may be useful in clinical practice for saving more living heart muscle in the area of myocardial infarction and improving cardiac function following the elective opening of obstructed coronary arteries.
