Punica Granatum Rind Extract: Antibiotic Potentiator and Efflux Pump Inhibitor of Multidrug Resistant Klebsiella Pneumoniae Clinical Isolates

Abstract

Objective: With a rise in multidrug resistant (MDR) bacterial isolates, search for antibiotics or compounds that could act synergistically with them is a significant area of research. Efflux-mediated resistance, in particular, is a great hurdle that needs to be overcome. In an effort to identify such synergistic compounds and potential efflux pump inhibitors (EPI), we analyzed the rind of Punica granatum (pomegranate) against MDR clinical Klebsiella pneumoniae isolates.Methods: Sequential fractionation of P. granatum rind ethanol (PGR) extract was carried out to obtain hexane, butanol and water fractions. Antibacterial activity of the plant extracts was confirmed, and synergistic interaction with antibiotics was determined by the checkerboard assay. Gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify the phytochemical constituents of the hexane extract. To study EPI activity of the extracts, norfloxacin accumulation assay was carried out.Results: PGR ethanol extract was found to have synergistic activity with ciprofloxacin, levofloxacin, ceftazidime, cefoxitin, meropenem, and gentamicin resulting in fold decrease of minimum inhibitory concentration (MIC) ranging from 2 to 32 fold. The hexane fraction was found to have maximum synergistic activity resulting in a 32-fold reduction of ciprofloxacin MIC followed by butanol and water fractions. The PGR ethanol extract was also found to have efflux inhibition activity by the norfloxacin accumulation assay. Of the sequential fractions, the butanol fraction had maximum efflux inhibition activity.Conclusion: Therefore, our study shows that PGR extract can potentiate the effect of antibiotics on MDR bacteria, and the mode of action is likely to be due to EPI.

Evaluation and Comparison of Antibacterial Efficacy of Herbal Extracts in Combination with Antibiotics on Periodontal pathobionts: An in vitro Microbiological Study

“…The outcome of combining two drugs can be synergistic, additive, or antagonistic depending on the interaction between drugs. Various in vitro experiments have established the fact that a combination of plant extracts and antibiotics possess a synergistic effect, which results in a significant decrease in levels of MIC for the antibiotics [48,49]. One of the main objectives of the current study was to estimate and establish the combined antibacterial activity of plant extracts with antibiotics against clinical strains of periodontal disease causing bacteria.…”

Antimicrobial Activity and Interactions of Toddalia asiatica Isolated Coumarins with Two Known Drugs

“…A number of phytochemicals have proven therapeutic potential as antimicrobial compounds and have also been shown to increase the susceptibility of the organism to various drugs [28,29,31]. In the current study, interaction in antimicrobial activity between two isolated compounds 1 and 3, and in combination with antimicrobial agents, gentamycin and fluconazole was evident.…”

“…A fourfold reduction in the MIC of gentamicin when combined with the phytochemicals, protocatechuic acid, quercetin, caffeic acid on one hand and by the same factor for sulfadiazine in combination with the same compounds on another, in their action against Pseudomonas aeruginosa have been revealed [28]. A 34-fold reduction of MIC of Klebsiella pneumoniae resistant in combination tests involving ethanol extract of Punica granatum rind with ciprofloxacin was demonstrated by Rafiq and coworkers [29]. Allicin, a phytochemical present in garlic, has been shown to work synergistically in combination with β-lactam antibiotics against Staphylococcus spp.…”

Anti-cancer Effects of Pomegranate Seed Oil on Esophageal Cancer Cell Line (KYSE-30)

“…Pomegranate juice and pomegranate oil have antioxidant and anti-inflammatory properties (9,11,16,44). Clinical studies have shown that pomegranate can prevent cancer cell growth in the skin, breast, and prostate (18,45,46). Several in vitro studies have also shown the therapeutic effects of pomegranate extracts on various cancer cells such as breast cancer (MB-MDA and MCF-7), oral cancer (CAL-27 and KB), colon cancer (HT-29), and lung cancer (19)(20)(21)47).…”

“…Pomegranate seed oil includes a high content of unsaturated fatty acids (e.g., linolenic, oleic acid, starchy acid, palmitic acid, punicic acid), which targets breast cancer cells and kills them usefully (11,16). It also contains antioxidant, anti-carcinogenic, antibacterial, and anti-inflammatory components, which can prevent and treat several cancers, such as colon, lung, and prostate cancer (11,(17)(18)(19)(20)(21).…”