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Antioxidant and Antidiabetic Activities, and UHPLC-ESI-QTOF-MS-Based Metabolite Profiling of an Endophytic Fungus Nigrospora sphaerica BRN 01 Isolated from Bauhinia purpurea L

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Abstract

Diabetes-associated postprandial hyperglycemia is a major risk factor in cardiovascular disease. Since enzyme α-glucosidase is primarily responsible for glucose release during digestion, inhibiting it mitigates post-meal spike in blood glucose level. Metabolites from endophytic fungi could be potential natural inhibitors of this enzyme. Endophytic fungi isolated from Bauhinia purpurea L. were screened for their potential antioxidant and antidiabetic activities. Ethyl acetate extract of Nigrospora sphaerica BRN 01 (NEE) displayed high antioxidant activity with an IC50 value of 9.72 ± 0.91 µg/ml for DPPH assay and ferric reducing antioxidant power (FRAP) of 1595 ± 0.23 µmol AAE g−1 DW. NEE also showed high degree of inhibition of α-glucosidase activity with an IC50 value of 0.020 ± 0.001 mg/ml, significantly greater than the standard drug acarbose (0.494 ± 0.009 mg/ml). Metabolite profiling of NEE was carried using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) and 21 metabolites identified based on the MS/MS fragmentation patterns. Docking analysis of all 21 identified metabolites was carried out. Of these, 6 showed binding energies higher than acarbose (− 6.6 kcal/mol). Based on the analysis of interactions of feruloyl glucose with active site residues of the enzyme, it could be a potential α-glucosidase inhibitor. Metabolites of Nigrospora sphaerica BRN 01, therefore, could be potential lead molecules for design and development of antidiabetic drugs.

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References

  1. IDF Diabetes Atlas | Tenth Edition. (n.d.). Retrieved from https://diabetesatlas.org/

  2. Hossain, U., Das, A. K., Ghosh, S., & Sil, P. C. (2020). An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications. Food and Chemical Toxicology, 145, 111738. https://doi.org/10.1016/J.FCT.2020.111738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Riyaphan, J., Pham, D. C., Leong, M. K., & Weng, C. F. (2021). In silico approaches to identify polyphenol compounds as α-glucosidase and α-amylase inhibitors against type-II diabetes. Biomolecules, 11(12), 1877. https://doi.org/10.3390/BIOM11121877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Akmal, M., & Wadhwa, R. (2022). Alpha glucosidase inhibitors. NCBI Bookshelf. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557848/

  5. Smith, D. L., Orlandella, R. M., Allison, D. B., & Norian, L. A. (2021). Diabetes medications as potential calorie restriction mimetics—A focus on the alpha-glucosidase inhibitor acarbose. GeroScience, 43(3), 1123–1133. https://doi.org/10.1007/S11357-020-00278-X/FIGURES/1

    Article  CAS  PubMed  Google Scholar 

  6. Uuh Narvaez, J. J., & Segura Campos, M. R. (2022). Combination therapy of bioactive compounds with acarbose: A proposal to control hyperglycemia in type 2 diabetes. Journal of Food Biochemistry, e14268. https://doi.org/10.1111/JFBC.14268

  7. Dirir, A. M., Daou, M., Yousef, A. F., & Yousef, L. F. (2021). A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes. Phytochemistry Reviews, 21(4), 1049–1079. https://doi.org/10.1007/S11101-021-09773-1

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wen, J., Okyere, S. K., Wang, S., Wang, J., Xie, L., Ran, Y., & Hu, Y. (2022). Endophytic fungi: An effective alternative source of plant-derived bioactive compounds for pharmacological studies. Journal of Fungi, 8(2), 205. https://doi.org/10.3390/JOF8020205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Benjamim, J., da Costa, K., Santos, A., & Santos, A. (2021). Chemical, botanical and pharmacological aspects of the Leguminosae. Pharmacognosy Reviews, 14(28), 106–120. https://doi.org/10.5530/phrev.2020.14.15

    Article  CAS  Google Scholar 

  10. Xu, T., Song, Z., Hou, Y., Liu, S., Li, X., Yang, Q., & Wu, S. (2022). Secondary metabolites of the genus Nigrospora from terrestrial and marine habitats: Chemical diversity and biological activity. Fitoterapia, 161, 105254. https://doi.org/10.1016/J.FITOTE.2022.105254

    Article  CAS  PubMed  Google Scholar 

  11. Suryanarayanan, T. S., Kumaresan, V., & Johnson, J. A. (1998). Foliar fungal endophytes from two species of the mangrove Rhizophora. Canadian Journal of Microbiologyicrobiology, 44(10), 1003–1006. https://doi.org/10.1139/W98-087

    Article  CAS  Google Scholar 

  12. Sharma, D., Pramanik, A., & Agrawal, P. K. (2016). Evaluation of bioactive secondary metabolites from endophytic fungus Pestalotiopsis neglecta BAB-5510 isolated from leaves of Cupressus torulosa D.Don. 3 Biotech, 6(2). https://doi.org/10.1007/S13205-016-0518-3

  13. Kumar, S., Stecher, G., Li, M., Knyaz, C., & Tamura, K. (2018). MEGA X: Molecular evolutionary genetics analysis across computing platforms. Molecular biology and evolution, 35(6), 1547–1549. https://doi.org/10.1093/MOLBEV/MSY096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tamura, K., Nei, M., & Kumar, S. (2004). Prospects for inferring very large phylogenies by using the neighbor-joining method. Proceedings of the National Academy of Sciences of the United States of America, 101(30), 11030–11035. https://doi.org/10.1073/PNAS.0404206101/ASSET/D0B973E3-6167-4566-B866-7A0FB0A0057B/ASSETS/GRAPHIC/ZPQ0300455080006.JPEG

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bulut, O., Akın, D., Sönmez, Ç., Öktem, A., Yücel, M., & Öktem, H. A. (2019). Phenolic compounds, carotenoids, and antioxidant capacities of a thermo-tolerant Scenedesmus sp. (Chlorophyta) extracted with different solvents. Journal of Applied Phycology, 31(3), 1675–1683. https://doi.org/10.1007/S10811-018-1726-5/TABLES/4

    Article  CAS  Google Scholar 

  16. Khor, B.-K., Jeng-YeouChear, N., Azizi, J., Khaw, K.-Y., Khor, B.-K., Chear, N., & Chemical, K.-Y. (2021). Chemical composition, antioxidant and cytoprotective potentials of Carica papaya leaf extracts: A comparison of supercritical fluid and conventional extraction methods. Molecules, 26(5), 1489. https://doi.org/10.3390/MOLECULES26051489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bhatia, A., Singh, B., Arora, R., & Arora, S. (2019). In vitro evaluation of the α-glucosidase inhibitory potential of methanolic extracts of traditionally used antidiabetic plants. BMC Complementary and Alternative Medicine, 19(1). https://doi.org/10.1186/s12906-019-2482-z

  18. Biswal, R. P., Dandamudi, R. B., Patnana, D. P., Pandey, M., & Vutukuri, V. N. R. K. (2022). Metabolic fingerprinting of Ganoderma spp using UHPLC-ESI-QTOF-MS and its chemometric analysis. Phytochemistry, 199, 113169. https://doi.org/10.1016/J.PHYTOCHEM.2022.113169

    Article  CAS  PubMed  Google Scholar 

  19. Sim, L., Quezada-Calvillo, R., Sterchi, E. E., Nichols, B. L., & Rose, D. R. (2008). Human intestinal maltase–glucoamylase: Crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. Journal of Molecular Biology, 375(3), 782–792. https://doi.org/10.1016/J.JMB.2007.10.069

    Article  CAS  PubMed  Google Scholar 

  20. Seeliger, D., & De Groot, B. L. (2010). Conformational transitions upon ligand binding: Holo-structure prediction from apo conformations. PLoS Computational Biology, 6(1). https://doi.org/10.1371/JOURNAL.PCBI.1000634

  21. Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/JCC.21334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ghanta, P., Sinha, S., Doble, M., & Ramaiah, B. (2020). Potential of pyrroquinazoline alkaloids from Adhatoda vasica Nees. as inhibitors of 5-LOX – a computational and an in-vitro study. https://doi.org/10.1080/07391102.2020.1848635, 40(6), 2785–2796. https://doi.org/10.1080/07391102.2020.1848635

  23. Hyun, T. K., Kim, H. C., & Kim, J. S. (2014). Antioxidant and antidiabetic activity of Thymus quinquecostatus Celak. Industrial Crops & Products, Complete(52), 611–616. https://doi.org/10.1016/J.INDCROP.2013.11.039

  24. Giacco, F., & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation research, 107(9), 1058. https://doi.org/10.1161/CIRCRESAHA.110.223545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Erenler, R., Telci, I., Ulutas, M., Demirtas, I., Gul, F., Elmastas, M., & Kayir, O. (2015). Chemical constituents, quantitative analysis and antioxidant activities of Echinacea purpurea (L.) Moench and Echinacea pallida (Nutt.) Nutt. Journal of Food Biochemistry, 39(5), 622–630. https://doi.org/10.1111/JFBC.12168

    Article  CAS  Google Scholar 

  26. Erenler, R., Sen, O., Aksit, H., Demirtas, I., Yaglioglu, A. S., Elmastas, M., & Telci, I. (2016). Isolation and identification of chemical constituents from Origanum majorana and investigation of antiproliferative and antioxidant activities. Journal of the Science of Food and Agriculture, 96(3), 822–836. https://doi.org/10.1002/JSFA.7155

    Article  CAS  PubMed  Google Scholar 

  27. Visavadiya, N. P., Soni, B., & Dalwadi, N. (2009). Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models. International Journal of Food Sciences and Nutrition, 60(SUPPL. 2), 135–149. https://doi.org/10.1080/09637480902877998

    Article  CAS  PubMed  Google Scholar 

  28. Rigane, G., Ghazghazi, H., Aouadhi, C., Ben Salem, R., & Nasr, Z. (2017). Phenolic content, antioxidant capacity and antimicrobial activity of leaf extracts from Pistacia atlantica. Natural Product Research, 31(6), 696–699. https://doi.org/10.1080/14786419.2016.1212035

    Article  CAS  PubMed  Google Scholar 

  29. Nadeem, M., Mumtaz, M. W., Danish, M., Rashid, U., Mukhtar, H., & Irfan, A. (2020). Antidiabetic functionality of Vitex negundo L. leaves based on UHPLC-QTOF-MS/MS based bioactives profiling and molecular docking insights. Industrial Crops and Products, 152, 112445. https://doi.org/10.1016/J.INDCROP.2020.112445

    Article  CAS  Google Scholar 

  30. Supaphon, P., & Preedanon, S. (2019). Evaluation of in vitro alpha-glucosidase inhibitory, antimicrobial, and cytotoxic activities of secondary metabolites from the endophytic fungus, Nigrospora sphaerica, isolated from Helianthus annuus. Annals of Microbiology, 69(13), 1397–1406. https://doi.org/10.1007/S13213-019-01523-1/TABLES/3

    Article  CAS  Google Scholar 

  31. Sharaf, M. H., Abdelaziz, A. M., Kalaba, M. H., Radwan, A. A., & Hashem, A. H. (2022). Antimicrobial, antioxidant, cytotoxic activities and phytochemical analysis of fungal endophytes isolated from Ocimum Basilicum. Applied Biochemistry and Biotechnology, 194(3), 1271–1289. https://doi.org/10.1007/S12010-021-03702-W/FIGURES/6

    Article  CAS  PubMed  Google Scholar 

  32. Robert, J. -, & Yardley, V. (2009). Drugs for neglected diseases initiative (DNDi). Swiss Tropical Institute (STI), Tanja Wenzler, Swiss Tropical Institute (STI): Reto Brun.

    Google Scholar 

  33. Ruttkies, C., Schymanski, E. L., Wolf, S., Hollender, J., & Neumann, S. (2016). MetFrag relaunched: Incorporating strategies beyond in silico fragmentation. Journal of Cheminformatics, 8(1). https://doi.org/10.1186/S13321-016-0115-9

  34. Nadeem, M., Mumtaz, M. W., Danish, M., Rashid, U., Mukhtar, H., & Irfan, A. (2020). Antidiabetic functionality of Vitex negundo L. leaves based on UHPLC-QTOF-MS/MS based bioactives profiling and molecular docking insights. Industrial Crops and Products, 152(April), 112445. https://doi.org/10.1016/j.indcrop.2020.112445

    Article  CAS  Google Scholar 

  35. Tanaka, T., Tanaka, T., & Tanaka, M. (2011). Potential cancer chemopreventive activity of protocatechuic acid. Journal of Experimental and Clinical Medicine, 3(1), 27–33. https://doi.org/10.1016/J.JECM.2010.12.005

    Article  CAS  Google Scholar 

  36. Adefegha, S. A., Oboh, G., Ejakpovi, I. I., & Oyeleye, S. I. (2015). Antioxidant and antidiabetic effects of gallic and protocatechuic acids: A structure–function perspective. Comparative Clinical Pathology, 24(6), 1579–1585. https://doi.org/10.1007/S00580-015-2119-7/FIGURES/7

    Article  CAS  Google Scholar 

  37. Kramberger, K., Barlič-Maganja, D., Bandelj, D., BarucaArbeiter, A., Peeters, K., MiklavčičVišnjevec, A., & Pražnikar, Z. J. (2020). HPLC-DAD-ESI-QTOF-MS determination of bioactive compounds and antioxidant activity comparison of the hydroalcoholic and water extracts from two Helichrysum italicum species. Metabolites, 10(10), 1–25. https://doi.org/10.3390/METABO10100403

    Article  Google Scholar 

  38. Chen, S., Liu, Z., Li, H., Xia, G., Lu, Y., He, L., & She, Z. (2015). β-Resorcylic acid derivatives with α-glucosidase inhibitory activity from Lasiodiplodia sp. ZJ-HQ1, an endophytic fungus in the medicinal plant Acanthus ilicifolius. Phytochemistry Letters, 13, 141–146. https://doi.org/10.1016/j.phytol.2015.05.019

    Article  CAS  Google Scholar 

  39. Huang, D. Y., Nong, X. H., Zhang, Y. Q., Xu, W., Sun, L. Y., Zhang, T., … Han, C. R. (2021). Two new 2,5-diketopiperazine derivatives from mangrove-derived endophytic fungus Nigrospora camelliae-sinensis S30. https://doi.org/10.1080/14786419.2021.1878168. https://doi.org/10.1080/14786419.2021.1878168

  40. Zhang, F., Li, B., Wen, Y., Liu, Y., Liu, R., Liu, J., & Jiang, Y. (2022). An integrated strategy for the comprehensive profiling of the chemical constituents of Aspongopus chinensis using UPLC-QTOF-MS combined with molecular networking. Pharmaceutical Biology, 60(1), 1349. https://doi.org/10.1080/13880209.2022.2096078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lan, H. C., Li, S. Z., Li, K., & Liu, E. H. (2021). In vitro human intestinal microbiota biotransformation of nobiletin using liquid chromatography–mass spectrometry analysis and background subtraction strategy. Journal of Separation Science, 44(10), 2046–2053. https://doi.org/10.1002/JSSC.202001150

    Article  CAS  PubMed  Google Scholar 

  42. Zhang, H., Deng, Z., Guo, Z., Tu, X., Wang, J., & Zou, K. (2014). Pestalafuranones F-J, Five new furanone analogues from the endophytic fungus Nigrospora sp. BM-2. Molecules, 19(1), 819–825. https://doi.org/10.3390/MOLECULES19010819

    Article  PubMed  PubMed Central  Google Scholar 

  43. Shen, Y., Liu, X., Yang, Y., Li, J., Ma, N., & Li, B. (2015). In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry. Biomedical Chromatography, 29(1), 129–137. https://doi.org/10.1002/BMC.3249

    Article  CAS  PubMed  Google Scholar 

  44. Zhang, X., Jia, Y., Ma, Y., Cheng, G., & Cai, S. (2018). Phenolic Composition, antioxidant properties, and inhibition toward digestive enzymes with molecular docking analysis of different fractions from Prinsepia utilis Royle fruits. Molecules, 23(12), 3373. https://doi.org/10.3390/MOLECULES23123373

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are ever grateful to the Founder Chancellor, Sri Sathya Sai Institute of Higher Learning (SSSIHL), Bhagawan Sri Sathya Sai Baba, for constant guidance and support. The authors are thankful to SSSIHL and UGC-SAP for providing financial support to carry out this work. The authors are grateful to Central Research Instrumentation Facility (CRIF), SSSIHL, for providing all necessary facilities. The authors wish to thank V. N. Ravi Kishore Vutukuri for the help provided in optimizing mass spectrometry protocols.

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  1. Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Brindavan Campus, Bengaluru, 560067, Karnataka, India

    Sai Anand Kannakazhi Kantari, Piyush Kumar, Malleswara Dharanikota & Ashok Agraharam

  2. Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam Campus, Puttaparthi, 515134, Andhra Pradesh, India

    Ranendra Pratap Biswal

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Contributions

Sai Anand Kannakazhi Kantari—development of methodologies and conducting investigations; data analysis and data presentation and writing the original draft.

Ranendra Pratap Biswal—development of methodology for LC–MS analysis.

Piyush Kumar—participated in conducting investigations.

Malleswara Dharanikota—providing some resources.

Ashok Agraharam—conception or design of the work, writing (review and editing), supervision.

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Correspondence to Ashok Agraharam.

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Kantari, S.A.K., Biswal, R.P., Kumar, P. et al. Antioxidant and Antidiabetic Activities, and UHPLC-ESI-QTOF-MS-Based Metabolite Profiling of an Endophytic Fungus Nigrospora sphaerica BRN 01 Isolated from Bauhinia purpurea L. Appl Biochem Biotechnol 195, 7465–7482 (2023). https://doi.org/10.1007/s12010-023-04452-7

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