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In vitro antibacterial activity of nimbolide against Helicobacter pylori

Wylie, Marina R. ; Windham, Ian H. ; Blum, Faith C. ; Wu, Hannah ; Merrell, D. Scott

Journal of ethnopharmacology, 2022-03, Vol.285, p.114828-114828, Article 114828 [Periódico revisado por pares]

Ireland: Elsevier B.V

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  • Título:
    In vitro antibacterial activity of nimbolide against Helicobacter pylori
  • Autor: Wylie, Marina R. ; Windham, Ian H. ; Blum, Faith C. ; Wu, Hannah ; Merrell, D. Scott
  • Assuntos: Anti-Bacterial Agents - pharmacology ; Antibacterial activity ; Azadirachta - chemistry ; Azadirachta indica ; Biofilms ; Drug Discovery ; Glycerides - pharmacology ; Helicobacter Infections - drug therapy ; Helicobacter pylori ; Helicobacter pylori - drug effects ; Humans ; Limonins - pharmacology ; Medicine, Traditional - methods ; Microbial Sensitivity Tests ; Neem oil extract ; Nimbolide ; Phytochemicals - pharmacology ; Plant Extracts - pharmacology ; Plant Leaves ; Terpenes - pharmacology
  • É parte de: Journal of ethnopharmacology, 2022-03, Vol.285, p.114828-114828, Article 114828
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Current address: Lyon College, Batesville, AR 72501, United States
    These authors contributed equally to this work.
    Authors’ contributions
    Current address: Division of Occupational Health and Safety, National Institutes of Health, Bethesda, MD 20892, United States
    Marina Wylie: Formal analysis, Investigation, Writing – Original Draft, Writing – Review & Editing, Visualization. Ian Windham: Conceptualization, Methodology, Investigation, Writing – Original Draft, Writing – Review & Editing, Supervision. Faith Blum: Conceptualization, Methodology, Investigation, Writing – Review & Editing. Hannah Wu: Investigation. D. Scott Merrell: Conceptualization, Writing – Review & Editing, Supervision, Funding acquisition.
  • Descrição: Nimbolide is one of hundreds of phytochemicals that have been identified within the neem tree (Azadirachta indica A. Juss). As an evergreen tree native to the Indian subcontinent, components of the neem tree have been used for millennia in traditional medicine to treat dental, gastrointestinal, urinary tract, and blood-related ailments, ulcers, headaches, heartburn, and diabetes. In modern times, natural oils and extracts from the neem tree have been found to have activities against a variety of microorganisms, including human pathogens. Aim of the study: Helicobacter pylori, a prevalent gastric pathogen, shows increasing levels of antibiotic resistance. Thus, there is an increasing demand for novel therapeutics to treat chronic infections. The in vitro activity of neem oil extract against H. pylori was previously characterized and found to be bactericidal. Given the numerous phytochemicals found in neem oil extract, the present study was designed to define and characterize specific compounds showing bactericidal activity against H. pylori. Azadirachtin, gedunin, and nimbolide, which are all common in neem extracts, were tested for antimicrobial activity; the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for nine strains of H. pylori. The specific properties of nimbolide were further characterized against H. pylori strain G27. Bactericidal kinetics, reversibility, effectiveness at low pH, and activity under bacteriostatic conditions were examined. The hemolytic activity of nimbolide was also measured. Finally, neem oil extract and nimbolide effectiveness against H. pylori biofilms were examined in comparison to common antibiotics used to treat H. pylori infection. Nimbolide, but not azadirachtin or gedunin, was effective against H. pylori; MICs and MBCs against the nine tested strains ranged between 1.25–5 μg/mL and 2.5–10 μg/mL, respectively. Additionally, neem oil extract and nimbolide were both effective against H. pylori biofilms. Nimbolide exhibited no significant hemolytic activity at biologically relevant concentrations. The bactericidal activity of nimbolide was time- and dose-dependent, independent of active H. pylori growth, and synergistic with low pH. Furthermore, nimbolide-mediated H. pylori cell death was irreversible after exposure to high nimbolide concentrations (80 μg/mL, after 2 h of exposure time and 40 μg/mL after 8 h of exposure). Nimbolide has significant bactericidal activity against H. pylori, killing both free living bacterial cells as well as cells within a biofilm. Furthermore, the lack of hemolytic activity, synergistic activity at low pH and bactericidal properties even against bacteria in a state of growth arrest are all ideal pharmacological and biologically relevant properties for a potential new agent. This study underscores the potential of neem oil extract or nimbolide to be used as a future treatment for H. pylori infection. [Display omitted] •Nimbolide has significant bactericidal activity against Helicobacter pylori.•This activity is synergistic with low pH and independent of growth state.•Nimbolide results in a post-antibiotic effect and is non-hemolytic.•Neem oil extract and nimbolide kill cells within established H. pylori biofilms.
  • Editor: Ireland: Elsevier B.V
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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