Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king
There is a growing demand for new diabetes drugs with fewer side effects to replace current medications known for their adverse effects. Inhibition of α-glucosidase responsible for postprandial hyperglycemia among diabetes patients is a promising strategy for managing the disease. This study aims to...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Fungal Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/ffunb.2025.1447609/full |
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| author | Piyush Kumar Sai Anand Kannakazhi Kantari Ranendra Pratap Biswal Prasanth Ghanta Malleswara Dharanikota |
| author_facet | Piyush Kumar Sai Anand Kannakazhi Kantari Ranendra Pratap Biswal Prasanth Ghanta Malleswara Dharanikota |
| author_sort | Piyush Kumar |
| collection | DOAJ |
| description | There is a growing demand for new diabetes drugs with fewer side effects to replace current medications known for their adverse effects. Inhibition of α-glucosidase responsible for postprandial hyperglycemia among diabetes patients is a promising strategy for managing the disease. This study aims to explore and identify novel bioactive metabolites with anti-diabetes potential from Alternaria alternata BRN05, an endophytic fungus isolated from a well-known medicinal plant Swietenia macrophylla King. Ethyl acetate extracts of Alternaria alternata BRN05 grown in full-strength (EFS) and quarter-strength (EQS) media, respectively were evaluated for their α-glucosidase inhibitory activities. Based on IC50 values, EQS exhibited significantly greater inhibitory activity (0.01482 ± 1.809 mg/mL) as compared to EFS (1.16 ± 0.173 mg/mL) as well as acarbose control (0.494 ± 0.009 mg/mL). EFS and EQS were subjected to metabolic profiling using Ultra-High-Performance Liquid Chromatography - Electrospray Ionization - Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-ESI-QTOF-MS). A total of nineteen metabolites from EFS and twenty from EQS were tentatively identified based on MS/MS fragmentation. Molecular docking analysis revealed that twelve among these exhibited greater binding energies than that of acarbose (-6.6 kcal/mol). Molecular Dynamics (MD) simulations of 3’,4’,7-trihydroxyisoflavanone (THF) and alternariol 9-methyl ether (AME) from EQS, exhibiting high binding energies (-7.5 and -7 kcal/mol, respectively), were performed to investigate their interactions with human intestinal α-glucosidase. Results suggest THF possesses strong inhibitory potential, making it a promising candidate for diabetes management. |
| format | Article |
| id | doaj-art-e219dc0f5960434e965a02aca94f3b69 |
| institution | Kabale University |
| issn | 2673-6128 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Fungal Biology |
| spelling | doaj-art-e219dc0f5960434e965a02aca94f3b692025-01-28T13:35:36ZengFrontiers Media S.A.Frontiers in Fungal Biology2673-61282025-01-01610.3389/ffunb.2025.14476091447609Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla kingPiyush Kumar0Sai Anand Kannakazhi Kantari1Ranendra Pratap Biswal2Prasanth Ghanta3Malleswara Dharanikota4Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, IndiaDepartment of Biosciences, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, IndiaResearch Executive Karkinos Healthcare, Navi Mumbai, Maharashtra, IndiaResearch Executive Karkinos Healthcare, Navi Mumbai, Maharashtra, IndiaDepartment of Biosciences, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, IndiaThere is a growing demand for new diabetes drugs with fewer side effects to replace current medications known for their adverse effects. Inhibition of α-glucosidase responsible for postprandial hyperglycemia among diabetes patients is a promising strategy for managing the disease. This study aims to explore and identify novel bioactive metabolites with anti-diabetes potential from Alternaria alternata BRN05, an endophytic fungus isolated from a well-known medicinal plant Swietenia macrophylla King. Ethyl acetate extracts of Alternaria alternata BRN05 grown in full-strength (EFS) and quarter-strength (EQS) media, respectively were evaluated for their α-glucosidase inhibitory activities. Based on IC50 values, EQS exhibited significantly greater inhibitory activity (0.01482 ± 1.809 mg/mL) as compared to EFS (1.16 ± 0.173 mg/mL) as well as acarbose control (0.494 ± 0.009 mg/mL). EFS and EQS were subjected to metabolic profiling using Ultra-High-Performance Liquid Chromatography - Electrospray Ionization - Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-ESI-QTOF-MS). A total of nineteen metabolites from EFS and twenty from EQS were tentatively identified based on MS/MS fragmentation. Molecular docking analysis revealed that twelve among these exhibited greater binding energies than that of acarbose (-6.6 kcal/mol). Molecular Dynamics (MD) simulations of 3’,4’,7-trihydroxyisoflavanone (THF) and alternariol 9-methyl ether (AME) from EQS, exhibiting high binding energies (-7.5 and -7 kcal/mol, respectively), were performed to investigate their interactions with human intestinal α-glucosidase. Results suggest THF possesses strong inhibitory potential, making it a promising candidate for diabetes management.https://www.frontiersin.org/articles/10.3389/ffunb.2025.1447609/fullα-glucosidase inhibitorsAlternaria alternatafull-strength media (FS)quarter-strength media (QS)diabetesultra-high-performance liquid chromatography - electrospray ionization - quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) |
| spellingShingle | Piyush Kumar Sai Anand Kannakazhi Kantari Ranendra Pratap Biswal Prasanth Ghanta Malleswara Dharanikota Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king Frontiers in Fungal Biology α-glucosidase inhibitors Alternaria alternata full-strength media (FS) quarter-strength media (QS) diabetes ultra-high-performance liquid chromatography - electrospray ionization - quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) |
| title | Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king |
| title_full | Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king |
| title_fullStr | Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king |
| title_full_unstemmed | Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king |
| title_short | Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria alternata BRN05 isolated from seeds of Swietenia macrophylla king |
| title_sort | elucidation of α glucosidase inhibitory activity and uhplc esi qtof ms based metabolic profiling of endophytic fungi alternaria alternata brn05 isolated from seeds of swietenia macrophylla king |
| topic | α-glucosidase inhibitors Alternaria alternata full-strength media (FS) quarter-strength media (QS) diabetes ultra-high-performance liquid chromatography - electrospray ionization - quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) |
| url | https://www.frontiersin.org/articles/10.3389/ffunb.2025.1447609/full |
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