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An O-methylflavone from Artemisia afra kills non-replicating hypoxic Mycobacterium tuberculosis

Ethnopharmacological relevance: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use.

Aim of the study: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium.

Materials and methods: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound.

Results: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc26230 in both log phase growth and metabolically downshifted hypoxic cultures.

Conclusions: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.

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Work Title An O-methylflavone from Artemisia afra kills non-replicating hypoxic Mycobacterium tuberculosis
Access
Open Access
Creators
  1. Joshua J. Kellogg
  2. Maria Natalia Alonso
  3. R. Teal Jordan
  4. Junpei Xiao
  5. Juan Hilario Cafiero
  6. Trevor Bush
  7. Xiaoling Chen
  8. Melissa Towler
  9. Pamela Weathers
  10. Scarlet S. Shell
Keyword
  1. Tuberculosis
  2. Biochemometrics
  3. Metabolomics
  4. Artemisia afra
  5. Infectious disease
  6. Hypoxia
License CC BY-NC-SA 4.0 (Attribution-NonCommercial-ShareAlike)
Work Type Article
Publisher
  1. Journal of Ethnopharmacology
Publication Date July 2, 2024
Publisher Identifier (DOI)
  1. 10.1016/j.jep.2024.118500
Related URLs
  1. https://doi.org/10.1016/j.jep.2024.118500
Deposited February 10, 2025

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Version 1
published

  • Created

    February 10, 2025 10:38 by jjk6146

  • Updated

    February 10, 2025 10:38 by [unknown user]

  • Added Creator Joshua J. Kellogg

    February 10, 2025 10:38 by jjk6146

  • Added Creator Maria Natalia Alonso

    February 10, 2025 10:38 by jjk6146

  • Added Creator R. Teal Jordan

    February 10, 2025 10:38 by jjk6146

  • Added Creator Junpei Xiao

    February 10, 2025 10:38 by jjk6146

  • Added Creator Juan Hilario Cafiero

    February 10, 2025 10:38 by jjk6146

  • Added Creator Trevor Bush

    February 10, 2025 10:38 by jjk6146

  • Added Creator Xiaoling Chen

    February 10, 2025 10:38 by jjk6146

  • Added Creator Melissa Towler

    February 10, 2025 10:38 by jjk6146

  • Added Creator Pamela Weathers

    February 10, 2025 10:38 by jjk6146

  • Added Creator Scarlet S. Shell

    February 10, 2025 10:38 by jjk6146

  • Updated Work Title, Keyword, Publisher, and 4 more Show Changes

    February 10, 2025 10:38 by jjk6146

    Work Title
    • An O-methylflavone from <i>Artemisia afra</i> kills non-replicating hypoxic <i>Mycobacterium tuberculosis</i>
    • An O-methylflavone from Artemisia afra kills non-replicating hypoxic Mycobacterium tuberculosis
    Keyword
    • Mycobacterium Tuberculosis, Artemisia, Non Replicating, Mycobacterium Tuberculosis (M. Tb), Antitubercular Activity, Extract, Tuberculosis, Transcriptomics, Diseases, Medicinal Plant, Mycobacterium Tuberculosis Strains, Biochemometrics, Active Compounds, Fever, Southern Africa, Artemisinin, Phytochemical, Fractionation, Phase Growth, Illness, Mechanistic Understanding, Mode Of Action, Methoxy, Log Phase, Transcriptome Analysis, Current Therapies, Phytochemicals, Artemisia Annua, Annua, Chromatographic Fractionation, Methoxyphenyl, Debilitating Disease, Emerging Drugs, Gene Expression Profiling, Gene Expression Assay
    Publisher
    • Journal of Ethnopharmacology
    Publisher Identifier (DOI)
    • 10.1016/j.jep.2024.118500
    Related URLs
    • https://doi.org/10.1016/j.jep.2024.118500
    Description
    • <p>Ethnopharmacological relevance: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use. Aim of the study: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium. Materials and methods: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound. Results: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc<sup>2</sup>6230 in both log phase growth and metabolically downshifted hypoxic cultures. Conclusions: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.</p>
    Publication Date
    • 2024-10-28
  • Updated

    February 10, 2025 10:38 by jjk6146

  • Updated

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Joshua J. Kellogg

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Maria Natalia Alonso

    February 10, 2025 10:38 by jjk6146

  • Updated Creator R. Teal Jordan

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Junpei Xiao

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Juan Hilario Cafiero

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Trevor Bush

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Xiaoling Chen

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Melissa Towler

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Pamela Weathers

    February 10, 2025 10:38 by jjk6146

  • Updated Creator Scarlet S. Shell

    February 10, 2025 10:38 by jjk6146

  • Added 1-s2.0-S0378874124007992-mmc1.xlsx

    February 10, 2025 10:39 by jjk6146

  • Added 1-s2.0-S0378874124007992-mmc2.docx

    February 10, 2025 10:39 by jjk6146

  • Added Kellogg et al_2024_An O-methylflavone from iArtemisia afra-i kills non-replicating hypoxic.pdf

    February 10, 2025 10:39 by jjk6146

  • Updated License Show Changes

    February 10, 2025 10:39 by jjk6146

    License
    • https://creativecommons.org/licenses/by-nc-sa/4.0/
  • Published

    February 10, 2025 10:39 by jjk6146

  • Updated

    February 10, 2025 21:04 by [unknown user]

  • Updated Keyword, Description, Publication Date Show Changes

    April 04, 2025 14:20 by avs5190

    Keyword
    • Mycobacterium Tuberculosis, Artemisia, Non Replicating, Mycobacterium Tuberculosis (M. Tb), Antitubercular Activity, Extract, Tuberculosis, Transcriptomics, Diseases, Medicinal Plant, Mycobacterium Tuberculosis Strains, Biochemometrics, Active Compounds, Fever, Southern Africa, Artemisinin, Phytochemical, Fractionation, Phase Growth, Illness, Mechanistic Understanding, Mode Of Action, Methoxy, Log Phase, Transcriptome Analysis, Current Therapies, Phytochemicals, Artemisia Annua, Annua, Chromatographic Fractionation, Methoxyphenyl, Debilitating Disease, Emerging Drugs, Gene Expression Profiling, Gene Expression Assay
    • Tuberculosis, Biochemometrics, Metabolomics, Artemisia afra, Infectious disease, Hypoxia
    Description
    • <p>Ethnopharmacological relevance: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use. Aim of the study: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium. Materials and methods: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound. Results: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc<sup>2</sup>6230 in both log phase growth and metabolically downshifted hypoxic cultures. Conclusions: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.</p>
    • <p>Ethnopharmacological relevance: African wormwood (_Artemisia afra_ Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of _A. afra_ may have contributed to its traditional medicinal use.
    • Aim of the study: Tuberculosis, caused by _Mycobacterium tuberculosis_ (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of _A. afra_ against Mtb, we sought to determine the mechanisms by which _A. afra_ inhibits and kills this bacterium.
    • Materials and methods: We used transcriptomics to investigate the impact of _Artemisia_ spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of _A. afra_ extracts and identify an active compound.
    • Results: Transcriptomic analysis revealed that _A. afra_ exerts different effects on Mtb compared to _A. annua_ or artemisinin, suggesting that _A. afra_ possesses other phytochemicals with unique modes of action. A biochemometric study of _A. afra_ resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc<sup>2</sup>6230 in both log phase growth and metabolically downshifted hypoxic cultures.
    • Conclusions: The present study demonstrated that an O-methylflavone constituent of _Artemisia afra_ explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of _A. afra_ and highlights the need for further study of this traditional medicinal plant and its active compounds.</p>
    Publication Date
    • 2024-10-28
    • 2024-07-02