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The Antimicrobial Potential of the Neem Tree Azadirachta indica.

ABSTRACT: Azadirachta indica (A. Juss), also known as the neem tree, has been used for millennia as a traditional remedy for a multitude of human ailments. Also recognized around the world as a broad-spectrum pesticide and fertilizer, neem has applications in agriculture and beyond. Currently, the extensive antimicrobial activities of A. indica are being explored through research in the fields of dentistry, food safety, bacteriology, mycology, virology, and parasitology. Herein, some of the most recent studies that demonstrate the potential of neem as a previously untapped source of novel therapeutics are summarized as they relate to the aforementioned research topics. Additionally, the capacity of neem extracts and compounds to act against drug-resistant and biofilm-forming organisms, both of which represent large groups of pathogens for which there are limited treatment options, are highlighted. Updated information on the phytochemistry and safety of neem-derived products are discussed as well. Although there is a growing body of exciting evidence that supports the use of A. indica as an antimicrobial, additional studies are clearly needed to determine the specific mechanisms of action, clinical efficacy, and in vivo safety of neem as a treatment for human pathogens of interest. Moreover, the various ongoing studies and the diverse properties of neem discussed herein may serve as a guide for the discovery of new antimicrobials that may exist in other herbal panaceas across the globe.

SUBMITTER: Wylie MR

PROVIDER: S-EPMC9195866 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The Antimicrobial Potential of the Neem Tree Azadirachta indica.

Wylie Marina R MR Merrell D Scott DS

Frontiers in pharmacology 20220530

Azadirachta indica (A. Juss), also known as the neem tree, has been used for millennia as a traditional remedy for a multitude of human ailments. Also recognized around the world as a broad-spectrum pesticide and fertilizer, neem has applications in agriculture and beyond. Currently, the extensive antimicrobial activities of A. indica are being explored through research in the fields of dentistry, food safety, bacteriology, mycology, virology, and parasitology. Herein, some of the ...[more]

PMID: 35712721

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Project description:BackgroundAntibiotic resistances of pathogens and breast cancer warrant the search for new alternative strategies. Phytoextracts can eradicate microbe-borne diseases as well as cancer with lower side effects compared to conventional antibiotics.AimUnripe and ripe Azadirachta indica (neem) seed extracts were explored as potential antibiofilm and anticancer agents in combating multidrug-resistant infectious bacteria as well as anticancer agents against the MDR breast cancer cell lines.MethodsShed-dried neem seeds (both unripe and ripe) were pulverized and extracted using methanol. The chemical components were identified with FTIR and gas chromatography - mass spectrometry. Antibiofilm activity of neem seed extracts were assessed in terms of minimum biofilm inhibitory concentration (MBIC), minimum biofilm eradication concentration (MBEC), and fluorescence microscopic studies on Staphylococcus aureus and Vibrio cholerae. Bacterial cells were studied by fluorescence microscopy using acridine orange/ethidium bromide as the staining agents. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were evaluated to observe the antibacterial activities. Cytotoxicity of the extracts against human blood lymphocytes and the anticancer activity against drug-resistant breast cancer cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and fluorescence-activated cell sorting (FACS) studies.Results4-Ethyl-2-hydroxy-2-cyclopentene-1-one, phthalic acid, and 2-hexyl-tetrahydro thiophane were the major compounds in unripe neem seed, whereas 3,5-dihydroxy-6-methyl-2,3-dihydro-4-H-pyran-4-one and 4-ethylbenzamide were predominant in ripe neem seed. Triazine derivatives were also common for both the extracts. MBIC values of unripe and ripe neem seed extracts for S. aureus are 75 and 100 µg/mL, respectively, and for V. cholerae, they are 100 and 300 µg/mL, respectively. MBEC values of unripe and ripe seed extracts are 500 and 300 µg/mL, respectively for S. aureus and for V. cholerae the values are 700 and 500 µg/mL, respectively. Fluorescence microscopic studies at 16 and 24 h, after bacterial culture, demonstrate enhanced antibiofilm activity for the ripe seed extract than that of the unripe seeds for both the bacteria. MTT assay reveals lower cytotoxicity of both the extracts towards normal blood lymphocytes, and anticancer activity against breast cancer cell line (MDA-MB-231) with superior activity of ripe seed extract. FACS studies further supported higher anticancer activity for ripe seed extract.ConclusionsMethanolic extract of neem seeds could substantially inhibit and eradicate biofilm along with their potent antibacterial and anticancer activities. Both the extracts showed higher antibiofilm and antibacterial activity against S. aureus (gram-positive) than V. cholerae (gram-negative). Moreover, ripe seed extract showed higher antibiofilm and anticancer activity than unripe extracts.

Project description:BackgroundNeem tree serves as a cornucopia for triterpenoids called limonoids that are of profound interest to humans due to their diverse biological activities. However, the biosynthetic pathway that plant employs for the production of limonoids remains unexplored for this wonder tree.ResultsHerein, we report the tracing of limonoid biosynthetic pathway through feeding experiments using 13C isotopologues of glucose in neem cell suspension. Growth and development specific limonoid spectrum of neem seedling and time dependent limonoid biosynthetic characteristics of cell lines were established. Further to understand the role of mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways in limonoid biosynthesis, Ultra Performance Liquid Chromatography (UPLC)- tandem mass spectrometry based structure-fragment relationship developed for limonoids and their isotopologues have been utilized. Analyses of labeled limonoid extract lead to the identification of signature isoprenoid units involved in azadirachtin and other limonoid biosynthesis, which are found to be formed through mevalonate pathway. This was further confirmed by treatment of cell suspension with mevinolin, a specific inhibitor for MVA pathway, which resulted in drastic decrease in limonoid levels whereas their biosynthesis was unaffected with fosmidomycin mediated plastidial methylerythritol 4-phosphate (MEP) pathway inhibition. This was also conspicuous, as the expression level of genes encoding for the rate-limiting enzyme of MVA pathway, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) was comparatively higher to that of deoxyxylulose-phosphate synthase (DXS) of MEP pathway in different tissues and also in the in vitro grown cells. Thus, this study will give a comprehensive understanding of limonoid biosynthetic pathway with differential contribution of MVA and MEP pathways.ConclusionsLimonoid biosynthesis of neem tree and cell lines have been unraveled through comparative quantification of limonoids with that of neem tree and through 13C limonoid isotopologues analysis. The undifferentiated cell lines of neem suspension produced a spectrum of C-seco limonoids, similar to parental tissue, kernel. Azadirachtin, a C-seco limonoid is produced in young tender leaves of plant whereas in the hard mature leaves of tree, ring intact limonoid nimocinol accumulates in high level. Furthermore, mevalonate pathway exclusively contributes for isoprene units of limonoids as evidenced through stable isotope labeling and no complementation of MEP pathway was observed with mevalonate pathway dysfunction, using chemical inhibitors.

Dataset Information

The Antimicrobial Potential of the Neem Tree Azadirachta indica.

Publications

The Antimicrobial Potential of the Neem Tree <i>Azadirachta indica</i>.

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