Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane

Abstract

Background:Clostridium difficile infection (CDI) has been widely reported in human and animals around the world over the past few decades. The high relapse rate and increasing drug resistance of CDI make the discovery of new agents against C. difficile fairly urgent. This study aims to investigate the antibacterial activity against C. difficile from traditional Chinese herb medicine Cullen corylifolium and confirm its active components.Methods: Phenolic extract from the seeds of C. corylifolium was prepared routinely and the contents of relative flavonoids were determined by High Performance Liquid Chromatography (HPLC). In vitro antibacterial activities of the phenolic extract and its major components were tested. The influence of the major components on cell membrane was investigated with membrane integrity by SEM and propidium iodid uptake assay. Cytotoxicity of the extract and its active compounds on Caco-2 cell line was assessed by CCK-8 kit. The in vivo therapeutic efficacy of IBCL was evaluated on the mice model.Results: Phenolic extract was found to be active against C. difficile with minimum inhibitory concentrations (MIC) of 8 μg/mL. As the major component of the extract, IBCL was the most active compound against C. difficile. The MIC of IBCL and 4MBCL were 4 μg/ml and 4 μg/ml, respectively. Meanwhile, PFPE, IBCL, and 4MBCL showed rapid bactericidal effect against C. difficile in 1 h, which was significant compared to antibiotic vancomycin. Mechanism studies revealed that IBCL can disrupt the integrity of the cell membrane, which may lead to the death of bacteria. PFPE was low cytotoxic against Caco-2 cells, and the cytotoxicity of IBCL and 4MBCL were moderate. Symptoms of CDI were effectively alleviated by IBCL on the mice model and weight loss was reduced. From death rates, IBCL showed better efficacy compared to vancomycin at 50 mg/kg dosage.Conclusion: As the major component of phenolic extract of C. corylifolium seeds, IBCL showed significant antibacterial activity against C. difficile in vitro and rapidly killed the bacteria by disrupting the integrity of the cell membrane. IBCL can significantly prevent weight loss and reduce death caused by CDI on the mice model. Therefore, IBCL may be a promising lead compound or drug candidate for CDI.

Flufenamic Acid, a Promising Agent for the Sensitization of Colistin-Resistant Gram-Negative Bacteria to Colistin

“…Following a 1-h incubation at 37°C in the dark, the OD 450 was measured on a microplate reader (Multiskan FC). FBS containing DMSO (the solvent used for FFA) as a vehicle control was used as a negative control ( 43 ). Three duplicates of every analysis were performed.…”

Advances on resources, biosynthesis pathway, bioavailability, bioactivity, and application of corylifolinin

“…Furthermore, corylifolinin has displayed substantial antibacterial activity against Clostridium difficile, marked by a minimum inhibitory concentration of 4 μg/mL. In contrast to the antibiotic vancomycin, corylifolinin exhibits a swifter bactericidal effect, attributed to its capacity to disrupt the integrity of the bacterial cell membrane (X. M. X. W. Liu et al, 2022).…”

“…W. Liu et al, 2022). In mouse models, corylifolinin has proven effective in ameliorating symptoms of C. difficile infection, reducing weight loss, and improving survival rates, outperforming vancomycin at a dose of 50 mg/kg (X. M. X. W. Liu et al, 2022).…”

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“…It is currently hypothesized that TCM may exert its antibacterial effects through various mechanisms, including the disruption of cell membrane structure to enhance permeability, elimination of plasmids carrying antibiotic resistance genes, modulation of cellular protein synthesis, interference with nucleic acid synthesis, and disruption of genetic code replication. [195][196][197] Yan et al conducted a comprehensive review on the utilization of TCM and its bioactive constituents for the treatment of AD. Their investigation encompassed animal models, pharmacodynamic mechanisms, and clinical studies.…”