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Vol. 35 No. 8 (2023): Vol 35 Issue 8, 2023

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Friedolanostanes from Garcinia benthamii Pierre: in silico Investigation of Anti-inflammatory Activity Targeting the NF-κB p50 Subunit

https://doi.org/10.14233/ajchem.2023.27960
Jasmine U. Ting
Department of Chemistry, De La Salle University, 2401 Taft Avenue, Manila 1004, Philippines
https://orcid.org/0000-0001-5361-2893
Consolacion Y. Ragasa
Department of Chemistry, De La Salle University, 2401 Taft Avenue, Manila 1004, Philippines
https://orcid.org/0000-0002-6687-6940
Romeo B. Lerom
Natural Sciences Department, College of Arts and Sciences, Western Philippines University, Aborlan, 5302, Philippines
https://orcid.org/0000-0001-5398-1453
Chien-Chang Shen
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, 155-1, Li-Nong St., Sec. 2, Taipei, Taiwan
https://orcid.org/0000-0001-9106-0698
Vincent Antonio S. Ng
Department of Chemistry, De La Salle University, 2401 Taft Avenue, Manila 1004, Philippines
https://orcid.org/0009-0005-0772-4217
Maria Carmen S. Tan
Department of Chemistry, De La Salle University, 2401 Taft Avenue, Manila 1004, Philippines
https://orcid.org/0000-0003-4413-5460
Glenn G. Oyong
Molecular Science Unit Laboratory, Center for Natural Science and Environmental Research, De La Salle University, 2401 Taft Avenue, Manila 1004, Philippines
https://orcid.org/0000-0001-8224-9034

Corresponding Author(s) : Glenn G. Oyong

glenn.oyong@dlsu.edu.ph

Asian Journal of Chemistry, Vol. 35 No. 8 (2023): Vol 35 Issue 8, 2023

Abstract

An investigation of the chemical constituents present in the dichloromethane (DCM) extracts of rind, fruit, roots and leaves of Garcinia benthamii Pierre has led to an isolation of a new triterpene (24E)-23-acetoxy-3α-hydroxylanosta-9(11),16,24-trien-26-oic acid (1), squalene and triacylglycerols from the roots; methyl (24E)-3α,9α,23-trihydroxy-17,14-friedolanosta-14,24-dien-26-oate (2), caryophyllene, squalene, a mixture of compound 1, (22Z,24E)-9α-hydroxy-3-oxo-17,14-friedolanosta-14,22,24-trien-26-oic acid (3) and another new triterpene (24E)-9α-hydroxy-3-oxo-17,14-friedolanosta-14,24-dien-26-oic acid (4) derived from pericarp; a combination of compound 3 and the new isolated triterpene methyl (24E)-9α,23-dihydroxy-3-oxo-17,14-friedolanosta-14,24-dien-26-oate (5), triacylglycerols, friedelin, squalene and a mixture of β-sitosterol and stigmasterol accrued from the outer covering of the stalk; compound 2, caryophyllene, α-carotene and chlorophyll a originating from the leaves; compound 2 and a blend of β-sitosterol and stigmasterol from the blooms; δ-tocotrienol, squalene and triacylglycerols from the mesocarp; and triacylglycerols and a composite of stigmasterol and β-sitosterol recovered from the seeds of G. benthamii. The molecular orientation of compound 1 was characterized by comprehensive 1D and 2D NMR examinations while compounds 2-5 were elucidated by 1D NMR spectroscopy since a new triterpene 4 was observed to have a small difference with compound 3 in C-22 and compound 5 was observed to have a difference with the C-3 signal of compound 2. To further examine the possible bioactivities of the friedolanostanes especially the new molecules, the anti-inflammatory potential of these compounds was predicted through docking analysis in Autodock Vina. Four of the identified friedolanostanes (2-5) were found to have higher binding affinities to NF-κB p50 homodimer than the control dexamethasone. Considering all the probable interactions of 9 amino acid residues, (Arg 57, Tyr 60, Glu 63, Lys 244, Pro 246, Lys 275, Arg 308, Gln 309 and Phe 310) perceivable binding mechanisms were observed to actively interact with the compounds either by conventional hydrogen bonding or by van der Waals forces. Further confirmation from the molecular dynamics study revealed that the stability of the protein-ligand complexes with compounds 2-5 had no significant conformational changes in the structure of the p50 homodimer. Hence, this study provided a chemical profile of the DCM extract obtained from the plant and propose a potential anti-inflammatory activity of the friedolanostanes through in silico investigation. Friedolanostanes (2-5) with promising anti-inflammatory activity may be synthesized and subjected to in vitro and in vivo investigation to establish the anti-inflammatory properties.

Keywords

Garcinia benthamii Pierre Garcinia ferrea Pierre Friedolanostanes Anti-inflammatory NF-κB p50
Ting, J. U., Ragasa, C. Y., Lerom, R. B., Shen, C.-C., Ng, V. A. S., Tan, M. C. S., & Oyong, G. G. (2023). Friedolanostanes from Garcinia benthamii Pierre: in silico Investigation of Anti-inflammatory Activity Targeting the NF-κB p50 Subunit. Asian Journal of Chemistry, 35(8), 1799–1809. https://doi.org/10.14233/ajchem.2023.27960
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References
  1. R.E. Coronel, Important and Underutilized Edible Fruits of the Philippines, UPLBFI and DA-BAR (2011).
  2. R.R. Lerom, J. Nat. Stud., 6, 49 (2007).
  3. R.R. Lerom, J. Nat. Stud., 3, 27 (2004).
  4. P.P. Goltenboth and F. Milan, A Guide to the Ecosystems of Palawan, Philippines, VISCA-GTZ Applied Tropical Ecology Program, Times Edition, Singapore (1998).
  5. B. Elya, H.P. He, S. Kosela, M. Hanafi and X.J. Hao, Nat. Prod. Res., 20, 1059 (2006); https://doi.org/10.1080/14786410500462512
  6. P. Amelia, B. Elya and M. Hanafi, Int. J. Pharm. Tech. Res., 7, 254 (2015).
  7. J.M. Joseph and T. Supinya, Afr. J. Biotechnol., 9, 1848 (2010); https://doi.org/10.5897/AJB10.660
  8. D.A. Bui, M.K. Vu, H.D. Nguyen, L.-T.T. Nguyen, S.V. Dang and L.-H.D. Nguyen, Phytochem. Lett., 10, 123 (2014); https://doi.org/10.1016/j.phytol.2014.08.019
  9. M.T. de Santana Souza, J.R. Almeida, A.A. de Souza Araujo, M.C. Duarte, D.P. Gelain, J.C. Moreira, M.R. dos Santos and L.J. Quintans-Júnior, Basic Clin. Pharmacol. Toxicol., 115, 244 (2014); https://doi.org/10.1111/bcpt.12221
  10. V.R. Yadav, S. Prasad, B. Sung, R. Kannappan and B.B. Aggarwal, Toxins, 2, 2428 (2010); https://doi.org/10.3390/toxins2102428
  11. Z.P. Wang, S.X. Cai, D.H. Liu, X. Xu and H. Liang, Acta Pharmacol. Sin., 27, 1474 (2006); https://doi.org/10.1111/j.1745-7254.2006.00442.x
  12. O. Trott and A.J. Olson, J. Comput. Chem., 31, 455 (2010); https://doi.org/10.1002/jcc.21334
  13. D. Schneidman-Duhovny, O. Dror, Y. Inbar, R. Nussinov and H.J. Wolfson, Nucleic Acids Res., 36(Web server), W223 (2008); https://doi.org/10.1093/nar/gkn187
  14. J. Dong, N.N. Wang, Z.J. Yao, L. Zhang, Y, Cheng, D, Ouyang, A,-P, Lu and D.-S. Cao, J. Cheminform., 10, 29 (2018); https://doi.org/10.1186/s13321-018-0283-x
  15. ACD/ChemSketch, version 2010.2.26; Advanced Chemistry Development, Inc.: O.N. Toronto, Canada (2010).
  16. Discovery Studio Visualizer, version 21.1.0.20298; Dassault Systèmes Biovia Corp: France (2020).
  17. R.J. Anderson, Z. Weng, R.K. Campbell and X. Jiang, Proteins, 60, 679 (2005); https://doi.org/10.1002/prot.20530
  18. I.W. Davis, A. Leaver-Fay, V.B. Chen, J.N. Block, G.J. Kapral, X. Wang, L.W. Murray, W.B. Arendall, J. Snoeyink, J.S. Richardson and D.C. Richardson, Nucleic Acids Res., 35(Web Server), W375 (2007); https://doi.org/10.1093/nar/gkm216
  19. A. Kuriata, A.M. Gierut, T. Oleniecki, M.P. Ciemny, A. Kolinski and M. Kurcinski, Nucleic Acids Res., 46(W1), W338 (2018); https://doi.org/10.1093/nar/gky356
  20. N.M. O’Boyle, M. Banck, C.A. James and C. Morley, J. Cheminform., 3, 33 (2011); https://doi.org/10.1186/1758-2946-3-33
  21. B. Bienfait and P. Ertl, J. Cheminform., 5, 24 (2013); https://doi.org/10.1186/1758-2946-5-24
  22. V. Rukachaisirikul, A. Adair, P. Dampawan, W.C. Taylor and P.C. Turner, Phytochemistry, 55, 183 (2000); https://doi.org/10.1016/S0031-9422(00)00191-6
  23. H.D. Nguyen, B.T.D. Trinh, Q.N. Tran, H.D. Nguyen, H.D. Pham, P.E. Hansen, F. Duus, J.D. Connolly and L.H.D. Nguyen, Phytochemistry, 72, 290 (2011); https://doi.org/10.1016/j.phytochem.2010.11.016
  24. C.Y. Ragasa, M.C.S. Tan, D. Fortin and C.C. Shen, J. Appl. Pharm. Sci., 5, 62 (2015); https://doi.org/10.7324/JAPS.2015.50912
  25. C.Y. Ragasa, O.B. Torres, J.M.P. Gutierrez, H.P.B.C. Kristiansen and C.C. Shen, J. Appl. Pharm. Sci., 5, 94 (2015); https://doi.org/10.7324/JAPS.2015.50416
  26. C.Y. Ragasa, D.L. Espineli, E.M. Agoo and R.S. del Fierro, Chin. J. Nat. Med., 11, 264 (2013).
  27. C.Y. Ragasa, V.A.S. Ng, V. Ebajo Jr, D. Fortin, M.M. De Los Reyes and C.C. Shen, Der Pharm. Lett., 6, 453 (2015).
  28. C.Y. Ragasa, V.A.S. Ng, M.M. De Los Reyes, E.H. Mandia, G.G. Oyong and C.C. Shen, Der Pharma Chem., 6, 182 (2014).
  29. J.M.C. Cayme and C.Y. Ragasa, Kimika, 20, 5 (2004); https://doi.org/10.26534/kimika.v20i1.5-12
  30. C.Y. Ragasa and J. de Jesus, Res. J. Pharm. Biol. Chem. Sci., 5, 701 (2014).
  31. E. Arnold, D.M. Himmel and M.G. Rossmann, International Tables for Crystallography: Crystallography of Biological Macromolecules, John Wiley & Sons: Chichester, U.K., edn. 1, vol. F, pp. 520-525 (2001).
  32. D. Eisenberg, R. Lüthy and J.U. Bowie, Methods Enzymol., 277, 396 (1997); https://doi.org/10.1016/S0076-6879(97)77022-8
  33. A. Messaoudi, H. Belguith and J. Ben Hamida, Theor. Biol. Med. Model., 10, 22 (2013); https://doi.org/10.1186/1742-4682-10-22
  34. B.C. Doak, B. Over, F. Giordanetto and J. Kihlberg, Chem. Biol., 21, 1115 (2014); https://doi.org/10.1016/j.chembiol.2014.08.013
  35. M. Varma, Pharmacol. Res., 48, 347 (2003); https://doi.org/10.1016/S1043-6618(03)00158-0
  36. A. Kaps, P. Gwiazdoñ and E. Chodurek, Molecules, 26, 1764 (2021); https://doi.org/10.3390/molecules26061764
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