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Synergistic antibacterial activity of Phyllanthus emblica fruits and its phytocompounds with ampicillin: a computational and experimental study

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Abstract

Phyllanthus emblica L. (syn. Emblica officinalis), popularly known as amla, Indian gooseberry, or the King of Rasyana, is a member of Phyllanthaceae family and is traditionally used in Ayurveda as an immunity booster. The present study aimed to investigate the synergistic interaction of Phyllanthus emblica (FPE) fruits and its selected phytocompounds with ampicillin against selected bacteria. Further, an in silico technique was used to find if major phytocompounds of FPE could bind to proteins responsible for antibiotic resistance in bacterial pathogens and enhance the bioactivity of ampicillin. FPE and all the selected phytocompounds were found to have synergistic antibacterial activity with ampicillin against tested bacteria in different combinations. However, ellagic acid and quercetin interactions with ampicillin resulted in maximum bioactivity enhancement of 32–128 folds and 16–277 folds, respectively. In silico analysis revealed strong ellagic acid, quercetin, and rutin binding with penicillin-binding protein (PBP-) 3, further supported by MD simulations. Ellagic acid and quercetin also fulfill Lipinski’s rule, showing similar toxicity characteristics to ampicillin. FPE showed synergistic interaction with ampicillin, possibly due to the presence of phytocompounds such as gallic acid, ellagic acid, quercetin, and rutin. Molecular docking and MD simulations showed the strong interaction of ellagic acid and quercetin with PBP-3 protein. Therefore, these compounds can be explored as potential non-toxic drug candidates to combat bacterial antimicrobial resistance.

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Acknowledgements

The authors are thankful to Shoolini University of Biotechnology and Management Sciences, Solan (HP), for providing the support.

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Authors and Affiliations

  1. Faculty of Applied Sciences and Biotechnology, Shoolini University of Biotechnology and Management Sciences, PO Sultanpur, Distt. Solan-173229 HP, Bajhol, India

    Rakshandha Saini, Anuradha Sourirajan & Kamal Dev

  2. University Institute of Biotechnology, Chandigarh University, Gharuan, Mohali, Punjab, 140413, India

    Vikas Kumar

  3. Department of Botany, Bioinformatics and Climate Change Impacts Management, University School of Science, Gujarat University, Ahmedabad, Gujarat, 380009, India

    Chirag N. Patel

  4. Biotechnology Research Center, Technology Innovation Institute, Masdar, Abu Dhabi, 9639, United Arab Emirates

    Chirag N. Patel

  5. Department of Pharmacology and Toxicology, Wright State University, Dayton, OH, 45435, USA

    Kamal Dev

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  1. Rakshandha Saini
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  2. Vikas Kumar
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  4. Anuradha Sourirajan
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Contributions

R.S. performed all the experiments and wrote the manuscript draft; V.K. contributed to the molecular docking, interpretation of results, and manuscript editing. C.N.P. performed MD simulations and interpretation of results; A.S. and K.D. supervised the study, interpretation of results, and final editing of the manuscript. All authors reviewed and approved the submission. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Vikas Kumar or Kamal Dev.

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Saini, R., Kumar, V., Patel, C.N. et al. Synergistic antibacterial activity of Phyllanthus emblica fruits and its phytocompounds with ampicillin: a computational and experimental study. Naunyn-Schmiedeberg's Arch Pharmacol 397, 857–871 (2024). https://doi.org/10.1007/s00210-023-02624-0

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