Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods

Abstract The rise of multidrug-resistant (MDR) microorganisms, particularly Escherichia coli, poses a significant threat to global public health, necessitating the development of alternative treatments. This study investigates the antibacterial properties of methanolic Punica granatum (pomegranate)...

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Main Authors: Faria Tasnim, Md. Eram Hosen, Al Riyad Hasan, Md. Taohid Hasan, Md. Mizanur Rahaman, Md. Motaher Hossain, Md. Abdulla Al Jubayed, Md. Aktaruzzaman, Mansour Altayyar, Endalamaw Yihune, Md. Tarikul Islam, Magdi E. A. Zaki
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02065-0
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author Faria Tasnim
Md. Eram Hosen
Al Riyad Hasan
Md. Taohid Hasan
Md. Mizanur Rahaman
Md. Motaher Hossain
Md. Abdulla Al Jubayed
Md. Aktaruzzaman
Mansour Altayyar
Endalamaw Yihune
Md. Tarikul Islam
Magdi E. A. Zaki
author_facet Faria Tasnim
Md. Eram Hosen
Al Riyad Hasan
Md. Taohid Hasan
Md. Mizanur Rahaman
Md. Motaher Hossain
Md. Abdulla Al Jubayed
Md. Aktaruzzaman
Mansour Altayyar
Endalamaw Yihune
Md. Tarikul Islam
Magdi E. A. Zaki
author_sort Faria Tasnim
collection DOAJ
description Abstract The rise of multidrug-resistant (MDR) microorganisms, particularly Escherichia coli, poses a significant threat to global public health, necessitating the development of alternative treatments. This study investigates the antibacterial properties of methanolic Punica granatum (pomegranate) leaf extract (MPGL) against MDR E. coli and explores its potential as a source of natural inhibitors for the CTX-M-9 beta-lactamase enzyme, a key contributor to antibiotic resistance. The disc diffusion assay revealed that MPGL exhibited significant antibacterial activity, with the highest inhibition zone of 16.67 ± 0.29 mm at 100 µg/disc. Additionally, an in silico approach was employed to identify potential inhibitors from P. granatum phytochemicals. Molecular docking studies demonstrated strong binding affinities of Epicatechin, Kaempferol, and Apigenin to the CTX-M-9 beta-lactamase protein (PDB ID: 1YLY), with binding energies of -6.25, -5.23, and − 5.21 kcal/mol, respectively. These compounds also showed favorable pharmacokinetic and toxicity profiles in ADMET analysis, indicating their potential as safe and effective therapeutic agents. Molecular dynamics simulations further confirmed the stability of these compounds in complex with the target protein over a 100 ns trajectory, with Epicatechin showing the most stable interactions. The study highlights the promising antibacterial activity of P. granatum leaf extract and identifies Epicatechin, Kaempferol, and Apigenin as potential lead compounds for developing novel therapies against MDR E. coli. These findings underscore the potential of plant-based compounds in combating antibiotic resistance and provide a foundation for further research into phytopharmaceuticals as alternative treatments for bacterial infections.
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publishDate 2025-05-01
publisher Nature Portfolio
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spelling doaj-art-b9fc54ea776d4ccea5ab6f44fea8c3b32025-08-20T03:48:19ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-02065-0Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methodsFaria Tasnim0Md. Eram Hosen1Al Riyad Hasan2Md. Taohid Hasan3Md. Mizanur Rahaman4Md. Motaher Hossain5Md. Abdulla Al Jubayed6Md. Aktaruzzaman7Mansour Altayyar8Endalamaw Yihune9Md. Tarikul Islam10Magdi E. A. Zaki11Department of Genetic Engineering and Biotechnology, University of RajshahiDepartment of Microbiology, Shaheed Shamsuzzoha Institute of Biosciences, Affiliated with University of RajshahiDepartment of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, University of RajshahiBiomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook UniversityDepartment of Microbiology, Rajshahi Institute of Biosciences, Affiliated with University of RajshahiDepartment of Microbiology, Rajshahi Institute of Biosciences, Affiliated with University of RajshahiBiomedical Sciences and Molecular Biology, College of Medicine and Dentistry, James Cook UniversityDepartment of Basic Medical Sciences, College of Medicine, University of JeddahDepartment of Biology, College of Science, Bahir Dar UniversityDepartment of Genetic Engineering and Biotechnology, Jashore University of Science and TechnologyDepartment of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University RiyadhAbstract The rise of multidrug-resistant (MDR) microorganisms, particularly Escherichia coli, poses a significant threat to global public health, necessitating the development of alternative treatments. This study investigates the antibacterial properties of methanolic Punica granatum (pomegranate) leaf extract (MPGL) against MDR E. coli and explores its potential as a source of natural inhibitors for the CTX-M-9 beta-lactamase enzyme, a key contributor to antibiotic resistance. The disc diffusion assay revealed that MPGL exhibited significant antibacterial activity, with the highest inhibition zone of 16.67 ± 0.29 mm at 100 µg/disc. Additionally, an in silico approach was employed to identify potential inhibitors from P. granatum phytochemicals. Molecular docking studies demonstrated strong binding affinities of Epicatechin, Kaempferol, and Apigenin to the CTX-M-9 beta-lactamase protein (PDB ID: 1YLY), with binding energies of -6.25, -5.23, and − 5.21 kcal/mol, respectively. These compounds also showed favorable pharmacokinetic and toxicity profiles in ADMET analysis, indicating their potential as safe and effective therapeutic agents. Molecular dynamics simulations further confirmed the stability of these compounds in complex with the target protein over a 100 ns trajectory, with Epicatechin showing the most stable interactions. The study highlights the promising antibacterial activity of P. granatum leaf extract and identifies Epicatechin, Kaempferol, and Apigenin as potential lead compounds for developing novel therapies against MDR E. coli. These findings underscore the potential of plant-based compounds in combating antibiotic resistance and provide a foundation for further research into phytopharmaceuticals as alternative treatments for bacterial infections.https://doi.org/10.1038/s41598-025-02065-0Antibacterial activityPunica granatumADMETMolecular DockingMolecular dynamics simulationCTX-M-9 beta-lactamase
spellingShingle Faria Tasnim
Md. Eram Hosen
Al Riyad Hasan
Md. Taohid Hasan
Md. Mizanur Rahaman
Md. Motaher Hossain
Md. Abdulla Al Jubayed
Md. Aktaruzzaman
Mansour Altayyar
Endalamaw Yihune
Md. Tarikul Islam
Magdi E. A. Zaki
Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
Scientific Reports
Antibacterial activity
Punica granatum
ADMET
Molecular Docking
Molecular dynamics simulation
CTX-M-9 beta-lactamase
title Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
title_full Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
title_fullStr Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
title_full_unstemmed Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
title_short Punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
title_sort punica granatum leaf extract as a natural antibacterial agent explored by experimental and computational methods
topic Antibacterial activity
Punica granatum
ADMET
Molecular Docking
Molecular dynamics simulation
CTX-M-9 beta-lactamase
url https://doi.org/10.1038/s41598-025-02065-0
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