Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Xi-Wang, Yang, Ya-Jun, Qin, Zhe, Li, Shi-Hong, Bai, Li-Xia, Ge, Wen-Bo, Li, Jian-Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356235/
https://www.ncbi.nlm.nih.gov/pubmed/35942219
http://dx.doi.org/10.3389/fphar.2022.914188
_version_ 1784763472887676928
author Liu, Xi-Wang
Yang, Ya-Jun
Qin, Zhe
Li, Shi-Hong
Bai, Li-Xia
Ge, Wen-Bo
Li, Jian-Yong
author_facet Liu, Xi-Wang
Yang, Ya-Jun
Qin, Zhe
Li, Shi-Hong
Bai, Li-Xia
Ge, Wen-Bo
Li, Jian-Yong
author_sort Liu, Xi-Wang
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9356235
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-93562352022-08-07 Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane Liu, Xi-Wang Yang, Ya-Jun Qin, Zhe Li, Shi-Hong Bai, Li-Xia Ge, Wen-Bo Li, Jian-Yong Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9356235/ /pubmed/35942219 http://dx.doi.org/10.3389/fphar.2022.914188 Text en Copyright © 2022 Liu, Yang, Qin, Li, Bai, Ge and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Liu, Xi-Wang
Yang, Ya-Jun
Qin, Zhe
Li, Shi-Hong
Bai, Li-Xia
Ge, Wen-Bo
Li, Jian-Yong
Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane
title Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane
title_full Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane
title_fullStr Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane
title_full_unstemmed Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane
title_short Isobavachalcone From Cullen corylifolium Presents Significant Antibacterial Activity Against Clostridium difficile Through Disruption of the Cell Membrane
title_sort isobavachalcone from cullen corylifolium presents significant antibacterial activity against clostridium difficile through disruption of the cell membrane
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356235/
https://www.ncbi.nlm.nih.gov/pubmed/35942219
http://dx.doi.org/10.3389/fphar.2022.914188
work_keys_str_mv AT liuxiwang isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane
AT yangyajun isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane
AT qinzhe isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane
AT lishihong isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane
AT bailixia isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane
AT gewenbo isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane
AT lijianyong isobavachalconefromcullencorylifoliumpresentssignificantantibacterialactivityagainstclostridiumdifficilethroughdisruptionofthecellmembrane