International Journal of

ADVANCED AND APPLIED SCIENCES

EISSN: 2313-3724, Print ISSN: 2313-626X

Frequency: 12

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 Volume 12, Issue 8 (August 2025), Pages: 90-100

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 Original Research Paper

Therapeutic potential of Moringa oleifera-derived isothiocyanates: Targeting adenosine A1 receptors in heart failure management

 Author(s): 

 Roaa M. Alreemi *

 Affiliation(s):

 Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia

 Full text

    Full Text - PDF

 * Corresponding Author. 

   Corresponding author's ORCID profile:  https://orcid.org/0000-0002-9062-5674

 Digital Object Identifier (DOI)

  https://doi.org/10.21833/ijaas.2025.08.009

 Abstract

Isothiocyanates (ITCs) are bioactive compounds found in various plants, including  Moringa oleifera, and are known for their health benefits, such as anticancer and anti-inflammatory effects. This study examines the interactions between four  Moringa oleifera-derived isothiocyanates (MITCs) and adenosine A1 receptors (A1R), which are important in cardiovascular, neurological, and other physiological functions. The SuperPred server was used for target prediction and confirmed a high binding probability of all MITC derivatives with A1R. Molecular docking analysis identified MITC-1 as the most promising compound based on its strong binding score. Further molecular dynamics (MD) simulations over 100 nanoseconds showed that the MITC-1–A1R complex had high binding affinity and remained stable, suggesting its potential as an A1R antagonist. Additionally, ADMET analysis indicated favorable drug-like properties for these compounds. These findings highlight the therapeutic potential of  Moringa oleifera-derived ITCs in treating heart failure and other A1R-related disorders, providing a basis for future laboratory and clinical research.

 © 2025 The Authors. Published by IASE.

 This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

 Keywords

 Isothiocyanates, Moringa oleifera, Adenosine A1 receptor, Molecular docking, Therapeutic potential

 Article history

 Received 13 October 2024, Received in revised form 12 February 2025, Accepted 11 July 2025

 Funding

This work was funded by the University of Jeddah, Jeddah, Saudi Arabia, under Grant No. (UJ-23-RSP-7). The author thanks the University of Jeddah for their technical and financial support. 

 Acknowledgment

No Acknowledgment. 

 Compliance with ethical standards

 Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

 Citation:

 Alreemi RM (2025). Therapeutic potential of Moringa oleifera-derived isothiocyanates: Targeting adenosine A1 receptors in heart failure management. International Journal of Advanced and Applied Sciences, 12(8): 90-100

  Permanent Link to this page

 Figures

  Fig. 1  Fig. 2  Fig. 3  Fig. 4  Fig. 5  Fig. 6  Fig. 7 

 Tables

  Table 1  Table 2  Table 3  Table 4

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 References (34)

  1. Alia F, Putri M, Anggraeni N, and Syamsunarno MRAA (2022). The potency of  Moringa oleifera Lam: As protective agent in cardiac damage and vascular dysfunction. Frontiers in Pharmacology, 12: 724439.  https://doi.org/10.3389/fphar.2021.724439    [Google Scholar] PMid:35140601 PMCid:PMC8818947
  2. Bahreyni A, Saeedi N, Al-Asady AM, Soleimani A, Ghorbani E, Khazaei M, Alaei M, Hanaei R, Ryzhikov M, Avan A, and Hassanian SM (2024). Therapeutic potency of A1 adenosine receptor antagonists in the treatment of cardiovascular diseases, current status and perspectives. Molecular Biology Reports, 51: 358.  https://doi.org/10.1007/s11033-024-09246-6    [Google Scholar] PMid:38400849
  3. Bai Y, Wang X, Zhao S, Ma C, Cui J, and Zheng Y (2015). Sulforaphane protects against cardiovascular disease via Nrf2 activation. Oxidative Medicine and Cellular Longevity, 2015: 407580.  https://doi.org/10.1155/2015/407580    [Google Scholar] PMid:26583056 PMCid:PMC4637098
  4. Basheer R, Strecker RE, Thakkar MM, and McCarley RW (2004). Adenosine and sleep–wake regulation. Progress in Neurobiology, 73(6): 379-396.  https://doi.org/10.1016/j.pneurobio.2004.06.004    [Google Scholar] PMid:15313333
  5. Borea PA, Gessi S, Merighi S, Vincenzi F, and Varani K (2018). Pharmacology of adenosine receptors: The state of the art. Physiological Reviews, 98(3): 1591-1625.  https://doi.org/10.1152/physrev.00049.2017    [Google Scholar] PMid:29848236
  6. Chen JF, Eltzschig HK, and Fredholm BB (2013). Adenosine receptors as drug targets—what are the challenges? Nature Reviews Drug Discovery, 12: 265-286.  https://doi.org/10.1038/nrd3955    [Google Scholar] PMid:23535933 PMCid:PMC3930074
  7. Cheng RK, Segala E, Robertson N, Deflorian F, Doré AS, Errey JC, Fiez-Vandal C, Marshall FH, and Cooke RM (2017). Structures of human A1 and A2A adenosine receptors with xanthines reveal determinants of selectivity. Structure, 25(8): 1275-1285.e4.  https://doi.org/10.1016/j.str.2017.06.012    [Google Scholar] PMid:28712806
  8. Dhalla AK, Shryock JC, Shreeniwas R, and Belardinelli L (2003). Pharmacology and therapeutic applications of A1 adenosine receptor ligands. Current Topics in Medicinal Chemistry, 3(4): 369-385.  https://doi.org/10.2174/1568026033392246    [Google Scholar] PMid:12570756
  9. Dinkova-Kostova AT and Kostov RV (2012). Glucosinolates and isothiocyanates in health and disease. Trends in Molecular Medicine, 18(6): 337-347.  https://doi.org/10.1016/j.molmed.2012.04.003    [Google Scholar] PMid:22578879
  10. Dunkel M, Günther S, Ahmed J, Wittig B, and Preissner R (2008). SuperPred: Drug classification and target prediction. Nucleic Acids Research, 36(suppl_2): W55-W59.  https://doi.org/10.1093/nar/gkn307    [Google Scholar] PMid:18499712 PMCid:PMC2447784
  11. Giacoppo S, Galuppo M, Montaut S, Iori R, Rollin P, Bramanti P, and Mazzon E (2015). An overview on neuroprotective effects of isothiocyanates for the treatment of neurodegenerative diseases. Fitoterapia, 106: 12-21.  https://doi.org/10.1016/j.fitote.2015.08.001    [Google Scholar] PMid:26254971
  12. Gottlieb SS, Ticho B, Deykin A, Abraham WT, DeNofrio D, Russell SD, Chapman D, Smith W, Goldman S, and Thomas I (2011). Effects of BG9928, an adenosine A1 receptor antagonist, in patients with congestive heart failure. The Journal of Clinical Pharmacology, 51: 899-907.  https://doi.org/10.1177/0091270010375957    [Google Scholar] PMid:20926754
  13. Hocher B (2010). Adenosine A1 receptor antagonists in clinical research and development. Kidney International, 78(5): 438-445.  https://doi.org/10.1038/ki.2010.204    [Google Scholar] PMid:20592713
  14. Ioakimidis L, Thoukydidis L, Mirza A, Naeem S, and Reynisson J (2008). Benchmarking the reliability of QikProp: Correlation between experimental and predicted values. QSAR and Combinatorial Science, 27: 445-456.  https://doi.org/10.1002/qsar.200730051    [Google Scholar]
  15. Jacobson KA and Gao ZG (2006). Adenosine receptors as therapeutic targets. Nature Reviews Drug Discovery, 5: 247-264.  https://doi.org/10.1038/nrd1983    [Google Scholar] PMid:16518376 PMCid:PMC3463109
  16. Jaja-Chimedza A, Graf BL, Simmler C, Kim Y, Kuhn P, Pauli GF, and Raskin I (2017). Biochemical characterization and anti-inflammatory properties of an isothiocyanate-enriched moringa ( Moringa oleifera) seed extract. PLOS ONE, 12(8): e0182658.  https://doi.org/10.1371/journal.pone.0182658    [Google Scholar] PMid:28792522 PMCid:PMC5549737
  17. Kamal RM, Abdull Razis AF, Mohd Sukri NS, Perimal EK, Ahmad H, Patrick R, Djedaini-Pilard F, Mazzon E, and Rigaud S (2022). Beneficial health effects of glucosinolates-derived isothiocyanates on cardiovascular and neurodegenerative diseases. Molecules, 27(3): 624.  https://doi.org/10.3390/molecules27030624    [Google Scholar] PMid:35163897 PMCid:PMC8838317
  18. Lopez-Rodriguez NA, Gaytán-Martínez M, de la Luz Reyes-Vega M, and Loarca-Piña G (2020). Glucosinolates and isothiocyanates from  Moringa oleifera: Chemical and biological approaches. Plant Foods for Human Nutrition, 75: 447-457.  https://doi.org/10.1007/s11130-020-00851-x    [Google Scholar] PMid:32909179
  19. Mastuo T, Miyata Y, Yuno T, Mukae Y, Otsubo A, Mitsunari K, Ohba K, and Sakai H (2020). Molecular mechanisms of the anti-cancer effects of isothiocyanates from cruciferous vegetables in bladder cancer. Molecules, 25(3): 575.  https://doi.org/10.3390/molecules25030575    [Google Scholar] PMid:32013065 PMCid:PMC7037050
  20. Na G, He C, Zhang S, Tian S, Bao Y, and Shan Y (2023). Dietary isothiocyanates: Novel insights into the potential for cancer prevention and therapy. International Journal of Molecular Sciences, 24(3): 1962.  https://doi.org/10.3390/ijms24031962    [Google Scholar] PMid:36768284 PMCid:PMC9916827
  21. Nguyen AT, Tran QL, Baltos JA, McNeill SM, Nguyen DT, and May LT (2023). Small molecule allosteric modulation of the adenosine A1 receptor. Frontiers in Endocrinology, 14: 1184360.  https://doi.org/10.3389/fendo.2023.1184360    [Google Scholar] PMid:37435481 PMCid:PMC10331460
  22. Olayanju JB, Bozic D, Naidoo U, and Sadik OA (2024). A comparative review of key isothiocyanates and their health benefits. Nutrients, 16(6): 757.  https://doi.org/10.3390/nu16060757    [Google Scholar] PMid:38542669 PMCid:PMC10974736
  23. Sahin N, Orhan C, Erten F, Tuzcu M, Defo Deeh PB, Ozercan IH, Juturu V, and Kazim S (2019). Effects of allyl isothiocyanate on insulin resistance, oxidative stress status, and transcription factors in high‐fat diet/streptozotocin‐induced type 2 diabetes mellitus in rats. Journal of Biochemical and Molecular Toxicology, 33: e22328.  https://doi.org/10.1002/jbt.22328    [Google Scholar] PMid:30927557
  24. Schenone S, Brullo C, Musumeci F, Bruno O, and Botta M (2010). A1 receptors ligands: Past, present and future trends. Current Topics in Medicinal Chemistry, 10(9): 878-901.  https://doi.org/10.2174/156802610791268729    [Google Scholar] PMid:20370661
  25. Schrödinger LLC (2024a). Schrödinger Release 2024‑3: Glide. Schrödinger, LLC, New York, USA. 
  26. Schrödinger LLC (2024b). Schrödinger Release 2024‑3: LigPrep. Schrödinger, LLC, New York, USA. 
  27. Schrödinger LLC (2024c). Schrödinger Release 2024‑3: Protein Preparation Wizard. Schrödinger, LLC, New York, USA. 
  28. Schrödinger LLC (2024d). Schrödinger Release 2024‑3: QikProp. Schrödinger, LLC, New York, USA.
  29. Sheth S, Brito R, Mukherjea D, Rybak LP, and Ramkumar V (2014). Adenosine receptors: Expression, function and regulation. International Journal of Molecular Sciences, 15(2): 2024-2052.  https://doi.org/10.3390/ijms15022024    [Google Scholar] PMid:24477263 PMCid:PMC3958836
  30. Tawfik HE, Schnermann J, Oldenburg PJ, and Mustafa SJ (2005). Role of A1 adenosine receptors in regulation of vascular tone. American Journal of Physiology-Heart and Circulatory Physiology, 288(3): H1411-H1416.  https://doi.org/10.1152/ajpheart.00684.2004    [Google Scholar] PMid:15539423
  31. Thai BS, Chia LY, Nguyen AT, Qin C, Ritchie RH, Hutchinson DS, Kompa A, White PJ, and May LT (2024). Targeting G protein‐coupled receptors for heart failure treatment. British Journal of Pharmacology, 181(14): 2270-2286.  https://doi.org/10.1111/bph.16099    [Google Scholar] PMid:37095602
  32. Vallon V, Miracle C, and Thomson S (2008). Adenosine and kidney function: Potential implications in patients with heart failure. European Journal of Heart Failure, 10: 176-187.  https://doi.org/10.1016/j.ejheart.2008.01.010    [Google Scholar] PMid:18242127 PMCid:PMC3151609
  33. Vincenzi F, Pasquini S, Contri C, Cappello M, Nigro M, Travagli A, Merighi S, Gessi S, Borea PA, and Varani K (2023). Pharmacology of adenosine receptors: Recent advancements. Biomolecules, 13(9): 1387.  https://doi.org/10.3390/biom13091387    [Google Scholar] PMid:37759787 PMCid:PMC10527030
  34. Waterman C, Cheng DM, Rojas-Silva P, Poulev A, Dreifus J, Lila MA, and Raskin I (2014). Stable, water extractable isothiocyanates from  Moringa oleifera leaves attenuate inflammation  in vitro. Phytochemistry, 103: 114-122.  https://doi.org/10.1016/j.phytochem.2014.03.028    [Google Scholar] PMid:24731259 PMCid:PMC4071966