Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte
Patients suffering from inflammatory chronic diseases are classically treated with anti-inflammatory drugs but unfortunately are highly susceptible to becoming resistant to their treatment. Finding new drugs is therefore crucial and urgent and research on endophytic fungi is a promising way forward....
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2023-09-01
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author | Rosella Spina Armelle Ropars Sihem Bouazzi Safa Dadi Pascal Lemiere François Dupire Afra Khiralla Sakina Yagi Jean-Pol Frippiat Dominique Laurain-Mattar |
author_facet | Rosella Spina Armelle Ropars Sihem Bouazzi Safa Dadi Pascal Lemiere François Dupire Afra Khiralla Sakina Yagi Jean-Pol Frippiat Dominique Laurain-Mattar |
author_sort | Rosella Spina |
collection | DOAJ |
description | Patients suffering from inflammatory chronic diseases are classically treated with anti-inflammatory drugs but unfortunately are highly susceptible to becoming resistant to their treatment. Finding new drugs is therefore crucial and urgent and research on endophytic fungi is a promising way forward. Endophytic fungi are microorganisms that colonize healthy plants and live within their intercellular tissues. They are able to produce a large variety of secondary metabolites while allowing their host to stay healthy. A number of these molecules are endowed with antioxidant or antimicrobial as well as cytotoxic properties, making them very interesting/promising in the field of human therapy. The aim of our study was to investigate whether extracts from five endophytic fungi isolated from plants are endowed with anti-inflammatory activity. Extracts of the endophytic fungi <i>Alternaria alternata</i> from <i>Calotropis procera</i> leaves and <i>Aspergillus terreus</i> from <i>Trigonella foenum-graecum</i> seeds were able to counteract the lipopolysaccharide (LPS) pro-inflammatory effect on THP-1 cells differentiated into macrophages. Moreover, they were able to induce an anti-inflammatory state, rendering them less sensitive to the LPS pro-inflammatory stimulus. Taken together, these results show that these both endophytic fungi could be interesting alternatives to conventional anti-inflammatory drugs. To gain more detailed knowledge of their chemical richness, phytochemical analysis of the ethyl acetate extracts of the five endophytic fungi studied was performed using HPTLC, GC-MS and LC-MS with the Global Natural Products Social (GNPS) platform and the MolNetEnhancer tool. A large family of metabolites (carboxylic acids and derivatives, steroid derivatives, alkaloids, hydroxyanthraquinones, valerolactones and perylenequinones) were detected. The purification of endophytic fungus extract of <i>Alternaria alternate,</i> which diminished TNF-α production of 66% at 20 µg/mL, incubated one hour before LPS addition, led to the characterization of eight pure compounds. These molecules are altertoxins I, II, III, tricycloalternarenes 3a, 1b, 2b, anthranilic acid, and <i>o</i>-acetamidobenzoic acid. In the future, all these pure compounds will be evaluated for their anti-inflammatory activity, while altertoxin II has been shown in the literature as the most active mycotoxin in terms of anti-inflammatory activity. |
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spelling | doaj.art-3855ecdcea2a4863af9a6a140ae1d4c62023-11-19T12:08:43ZengMDPI AGMolecules1420-30492023-09-012818653110.3390/molecules28186531Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria EndophyteRosella Spina0Armelle Ropars1Sihem Bouazzi2Safa Dadi3Pascal Lemiere4François Dupire5Afra Khiralla6Sakina Yagi7Jean-Pol Frippiat8Dominique Laurain-Mattar9Université de Lorraine, INRAE, LAE, F-54000 Nancy, FranceUniversité de Lorraine, SIMPA, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceUniversité de Lorraine, CNRS, L2CM, F-54000 Nancy, FranceBotany Department, Faculty of Sciences and Technologies, Shendi University, Shendi 11111, SudanDepartment of Botany, Faculty of Science, University of Khartoum, Khartoum 11115, SudanUniversité de Lorraine, SIMPA, F-54000 Nancy, FranceUniversité de Lorraine, INRAE, LAE, F-54000 Nancy, FrancePatients suffering from inflammatory chronic diseases are classically treated with anti-inflammatory drugs but unfortunately are highly susceptible to becoming resistant to their treatment. Finding new drugs is therefore crucial and urgent and research on endophytic fungi is a promising way forward. Endophytic fungi are microorganisms that colonize healthy plants and live within their intercellular tissues. They are able to produce a large variety of secondary metabolites while allowing their host to stay healthy. A number of these molecules are endowed with antioxidant or antimicrobial as well as cytotoxic properties, making them very interesting/promising in the field of human therapy. The aim of our study was to investigate whether extracts from five endophytic fungi isolated from plants are endowed with anti-inflammatory activity. Extracts of the endophytic fungi <i>Alternaria alternata</i> from <i>Calotropis procera</i> leaves and <i>Aspergillus terreus</i> from <i>Trigonella foenum-graecum</i> seeds were able to counteract the lipopolysaccharide (LPS) pro-inflammatory effect on THP-1 cells differentiated into macrophages. Moreover, they were able to induce an anti-inflammatory state, rendering them less sensitive to the LPS pro-inflammatory stimulus. Taken together, these results show that these both endophytic fungi could be interesting alternatives to conventional anti-inflammatory drugs. To gain more detailed knowledge of their chemical richness, phytochemical analysis of the ethyl acetate extracts of the five endophytic fungi studied was performed using HPTLC, GC-MS and LC-MS with the Global Natural Products Social (GNPS) platform and the MolNetEnhancer tool. A large family of metabolites (carboxylic acids and derivatives, steroid derivatives, alkaloids, hydroxyanthraquinones, valerolactones and perylenequinones) were detected. The purification of endophytic fungus extract of <i>Alternaria alternate,</i> which diminished TNF-α production of 66% at 20 µg/mL, incubated one hour before LPS addition, led to the characterization of eight pure compounds. These molecules are altertoxins I, II, III, tricycloalternarenes 3a, 1b, 2b, anthranilic acid, and <i>o</i>-acetamidobenzoic acid. In the future, all these pure compounds will be evaluated for their anti-inflammatory activity, while altertoxin II has been shown in the literature as the most active mycotoxin in terms of anti-inflammatory activity.https://www.mdpi.com/1420-3049/28/18/6531endophytic fungianti-inflammatory activitymolecular networkGNPS<i>Alternaria alternata</i>perylenequinones |
spellingShingle | Rosella Spina Armelle Ropars Sihem Bouazzi Safa Dadi Pascal Lemiere François Dupire Afra Khiralla Sakina Yagi Jean-Pol Frippiat Dominique Laurain-Mattar Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte Molecules endophytic fungi anti-inflammatory activity molecular network GNPS <i>Alternaria alternata</i> perylenequinones |
title | Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte |
title_full | Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte |
title_fullStr | Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte |
title_full_unstemmed | Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte |
title_short | Screening of Anti-Inflammatory Activity and Metabolomics Analysis of Endophytic Fungal Extracts; Identification and Characterization of Perylenequinones and Terpenoids from the Interesting Active Alternaria Endophyte |
title_sort | screening of anti inflammatory activity and metabolomics analysis of endophytic fungal extracts identification and characterization of perylenequinones and terpenoids from the interesting active alternaria endophyte |
topic | endophytic fungi anti-inflammatory activity molecular network GNPS <i>Alternaria alternata</i> perylenequinones |
url | https://www.mdpi.com/1420-3049/28/18/6531 |
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