Evaluating the anti-inflammatory potential of Mesua ferrea linn. stem bark through network pharmacology approach

Jyothsna Kalyana Sundaram; Manjunatha Hanumanthappa; Shivananada Kandagalla; Sharath Belenahalli Shekarappa; Pavan Gollapalli; Umme Hani

doi:10.7324/JABB.2023.11521

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Abstract

Mesua ferrea Linn. (MF) is a medicinal plant whose stem bark has historically been used to treat skin disorders, gastrointestinal, and anti-inflammatory conditions. Although the MF stem bark’s contribution to inflammation was assessed, its exact mode of action remained unknown. This study aimed to investigate the pharmacological mechanisms of MF against inflammation utilizing network pharmacology, molecular docking, and molecular dynamics (MD) simulation. An integrated network pharmacology approach was used to predict the pharmacological basis and potential mechanisms by which these ingredients may treat and prevent inflammation. This approach included target identification, network construction, topological analysis, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, molecular docking, and MD simulation. Utilizing the pre- Absorption, Distribution, Metabolism, Elimination, and Toxicity tool, the drug-likeness of the phytoconstituents was evaluated. Protein-protein interaction network and protein interaction network was constructed. The results indicated that androgen receptor, Estrogen Receptor alpha, CYP19A1, retinoic acid receptor alpha, nuclear factor erythroid 2-related factor 2, thyrotropin receptor, nuclear factor kappa B subunit 1, and Albumin are crucial proteins engaged directly or indirectly in inflammatory pathways and illnesses. Finally, the targets are validated by molecular docking and MD simulation. MF may be effective for alleviating inflammatory conditions and the mechanism of action is characterized by multi-compound, multi-target, and multi-pathways. Thus, our study provides certain evidence for the development and utilization of medicinal plants.

Keyword: Mesua ferrea Network pharmacology Gene ontology Molecular docking MD simulation

Citation:

Sundaram JK, Hanumanthappa M, Kandagalla S, Shekarappa SB, Gollapalli P, Hani U. Evaluating the anti-inflammatory potential of Mesua ferrea linn. stem bark through network pharmacology approach. J App Biol. 2023. Online First. http://doi.org/10.7324/JABB.2023.11521

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

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Reference

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2. Noor F, Qamar MT, Ashfaq UA, Albutti A, Alwashmi AS, Aljasir MA. Network pharmacology approach for medicinal plants: Review and assessment. Pharmaceuticals 2022;15:572. https://doi.org/10.3390/ph15050572
3. Dong Y, Zhao Q, Wang Y. Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy. Sci Rep 2021;111:19496. https://doi.org/10.1038/s41598-021-98925-6
4. Saeidnia S, Manayi A, Abdollahi M. The pros and cons of the in-silico pharmaco-toxicology in drug discovery and development. Int J Pharmacol 2013;9:176-81. https://doi.org/10.3923/ijp.2013.176.181
5. Rahman SM, Shabnom S, Quader MA, Hossain MA. Phytochemical study on the ethylacetate extract of the leaves of Mesua ferrea Linn. Indones J Chem 2010;8:242-4. https://doi.org/10.22146/ijc.21637
6. Asif M, Jafari SF, Iqbal Z, Revadigar V, Oon CE, Majid AS, et al. Ethnobotanical and Phytopharmacological attributes of Mesua ferrea: A mini review. J Appl Pharm Sci 2017;7:242-51.
7. Keawsa-Ard S, Liawruangrath B, Kongtaweelert S. Bioactive compounds from Mesua ferrea stems. Chiang Mai J Sci 2015;42:186-96.
8. Chahar MK, Kumar DS, Lokesh T, Manohara KP. In-vivo antioxidant and immunomodulatory activity of mesuol isolated from Mesua ferrea L. seed oil. Int Immunopharmacol 2012;13:386-91. https://doi.org/10.1016/j.intimp.2012.05.006
9. Chanda S, Rakholiya K, Parekh J. Indian medicinal herb: Antimicrobial efficacy of Mesua ferrea L. seed extracted in different solvents against infection causing pathogenic strains. J Acute Dis 2013;2:277-81. https://doi.org/10.1016/S2221-6189(13)60143-2
10. Mazumder R, Dastidar SG, Basu SP, Mazumder A, Singh SK. Antibacterial potentiality of Mesua ferrea Linn. flowers. Phyther Res 2004;18:824-6. https://doi.org/10.1002/ptr.1572
11. Prathima R, Manjunatha H, Krishna V, Kandagalla S, Sharath BS. Studies on anti-inflammatory effect of Mesua ferrea Linn. in acute and chronic inflammation of experimental animals. Int J Pharm Sci Res 2018;9:517-25.
12. Asif M, Shafaei A, Majid AS, Ezzat MO, Dahham SS, Ahamed MB, et al. Mesua ferrea stem bark extract induces apoptosis and inhibits metastasis in human colorectal carcinoma HCT 116 cells, through modulation of multiple cell signalling pathways. Chin J Nat Med 2017;15:505-14. https://doi.org/10.1016/S1875-5364(17)30076-6
13. Chaithanya KK, Gopalakrishnan VK, Hagos Z, Nagaraju B, Kamalakararao K, Kebede H, et al. In vitro and in vivo anti-inflammatory activities of Mesua ferrea Linn. Int J Pharmacogn Phytochem Res 2018;10:103-11. https://doi.org/10.25258/phyto.v10i03.11940
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22. Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61. https://doi.org/10.1002/jcc.21334
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28. Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for traditional Chinese medicine: review and assessment. Front
Pharmacol 2019;10:123. https://doi.org/10.12968/vetn.2019.10.3.123
29. Dirajlal-Fargo S, Kulkarni M, Bowman E, Shan L, Sattar A, Funderburg N, et al. Serum albumin is associated with higher inflammation and carotid atherosclerosis in treated human immunodeficiency virus infection. Open Forum Infect Dis 2018;5:ofy291. https://doi.org/10.1093/ofid/ofy291
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Sundaram J K [PubMed] [Google Scholar ]

Hanumanthappa M [PubMed] [Google Scholar ]

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By article title

1. Vodovotz Y, Constantine G, Rubin J, Csete M, Voit EO, An G. Mechanistic simulations of inflammation: Current state and future prospects. Math Biosci 2009;217:1-10. https://doi.org/10.1016/j.mbs.2008.07.013

2. Noor F, Qamar MT, Ashfaq UA, Albutti A, Alwashmi AS, Aljasir MA. Network pharmacology approach for medicinal plants: Review and assessment. Pharmaceuticals 2022;15:572. https://doi.org/10.3390/ph15050572

3. Dong Y, Zhao Q, Wang Y. Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy. Sci Rep 2021;111:19496. https://doi.org/10.1038/s41598-021-98925-6

4. Saeidnia S, Manayi A, Abdollahi M. The pros and cons of the in-silico pharmaco-toxicology in drug discovery and development. Int J Pharmacol 2013;9:176-81. https://doi.org/10.3923/ijp.2013.176.181

5. Rahman SM, Shabnom S, Quader MA, Hossain MA. Phytochemical study on the ethylacetate extract of the leaves of Mesua ferrea Linn. Indones J Chem 2010;8:242-4. https://doi.org/10.22146/ijc.21637

6. Asif M, Jafari SF, Iqbal Z, Revadigar V, Oon CE, Majid AS, et al. Ethnobotanical and Phytopharmacological attributes of Mesua ferrea: A mini review. J Appl Pharm Sci 2017;7:242-51.

7. Keawsa-Ard S, Liawruangrath B, Kongtaweelert S. Bioactive compounds from Mesua ferrea stems. Chiang Mai J Sci 2015;42:186-96.

8. Chahar MK, Kumar DS, Lokesh T, Manohara KP. In-vivo antioxidant and immunomodulatory activity of mesuol isolated from Mesua ferrea L. seed oil. Int Immunopharmacol 2012;13:386-91. https://doi.org/10.1016/j.intimp.2012.05.006

9. Chanda S, Rakholiya K, Parekh J. Indian medicinal herb: Antimicrobial efficacy of Mesua ferrea L. seed extracted in different solvents against infection causing pathogenic strains. J Acute Dis 2013;2:277-81. https://doi.org/10.1016/S2221-6189(13)60143-2

10. Mazumder R, Dastidar SG, Basu SP, Mazumder A, Singh SK. Antibacterial potentiality of Mesua ferrea Linn. flowers. Phyther Res 2004;18:824-6. https://doi.org/10.1002/ptr.1572

11. Prathima R, Manjunatha H, Krishna V, Kandagalla S, Sharath BS. Studies on anti-inflammatory effect of Mesua ferrea Linn. in acute and chronic inflammation of experimental animals. Int J Pharm Sci Res 2018;9:517-25.

12. Asif M, Shafaei A, Majid AS, Ezzat MO, Dahham SS, Ahamed MB, et al. Mesua ferrea stem bark extract induces apoptosis and inhibits metastasis in human colorectal carcinoma HCT 116 cells, through modulation of multiple cell signalling pathways. Chin J Nat Med 2017;15:505-14. https://doi.org/10.1016/S1875-5364(17)30076-6

13. Chaithanya KK, Gopalakrishnan VK, Hagos Z, Nagaraju B, Kamalakararao K, Kebede H, et al. In vitro and in vivo anti-inflammatory activities of Mesua ferrea Linn. Int J Pharmacogn Phytochem Res 2018;10:103-11. https://doi.org/10.25258/phyto.v10i03.11940

14. Singh S, Gray AI, Waterman PG. Mesuabixanthone-A and mesuabixanthone-B: Novel bis-xanthones from the stem bark of Mesua ferrea (Guttiferae). Nat Prod Lett 2006;3:53-8. https://doi.org/10.1080/10575639308043837

15. Islam R, Ahmed I, Sikder AA, Haque MR, Al-Mansur A, Ahmed M, et al. Chemical investigation of Mesua nagassarium (Burm. f.) kosterm. J Basic Appl Sci 2014;10:124-8. https://doi.org/10.6000/1927-5129.2014.10.17

16. Gaulton A, Hersey A, Nowotka ML, Bento AP, Chambers J, Mendez D, et al. The ChEMBL database in 2017. Nucleic Acids Res 2017;45:D945-54. https://doi.org/10.1093/nar/gkw1074

17. Filimonov DA, Lagunin AA, Gloriozova TA, Rudik AV, Druzhilovskii DS, Pogodin PV, et al. Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chem Heterocycl Compd 2014;50:444-57. https://doi.org/10.1007/s10593-014-1496-1

18. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-504. https://doi.org/10.1101/gr.1239303

19. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: Protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013;41:D808-15. https://doi.org/10.1093/nar/gks1094

20. Assenov Y, Ramírez F, Schelhorn SE, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinformatics 2008;24:282-4. https://doi.org/10.1093/bioinformatics/btm554

21. Ge SX, Jung D, Yao R. ShinyGO: A graphical gene-set enrichment tool for animals and plants. Bioinformatics 2020;36:2628-9. https://doi.org/10.1093/bioinformatics/btz931

22. Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61. https://doi.org/10.1002/jcc.21334

23. Laskowski RA, Swindells MB. LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 2011;51:2778-86. https://doi.org/10.1021/ci200227u

24. Hess B, Bekker H, Berendsen HJ, Fraaije JG. LINCS: A linear constraint solver for molecular simulations. J Comput Chem 1997;18:1463-72. https://doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H

25. Jin Z, Wang Y, Yu XF, Tan QQ, Liang SS, Li T, et al. Structure-based virtual screening of influenza virus RNA polymerase inhibitors from natural compounds: Molecular dynamics simulation and MM-GBSA calculation. Comput Biol Chem 2020;85:107241. https://doi.org/10.1016/j.compbiolchem.2020.107241

26. Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Biol 2002;9:646-52. https://doi.org/10.1038/nsb0902-646

27. Hedin U, Matic LP. Recent advances in therapeutic targeting of inflammation in atherosclerosis. J Vasc Surg 2019;69:944-51. https://doi.org/10.1016/j.jvs.2018.10.051

28. Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for traditional Chinese medicine: review and assessment. Front

Pharmacol 2019;10:123. https://doi.org/10.12968/vetn.2019.10.3.123

29. Dirajlal-Fargo S, Kulkarni M, Bowman E, Shan L, Sattar A, Funderburg N, et al. Serum albumin is associated with higher inflammation and carotid atherosclerosis in treated human immunodeficiency virus infection. Open Forum Infect Dis 2018;5:ofy291. https://doi.org/10.1093/ofid/ofy291

30. Cai Z, Liu J, Bian H, Cai J. Albiflorin alleviates ovalbumin (OVA)- induced pulmonary inflammation in asthmatic mice. Am J Transl Res 2019;11:7300-9.

31. Van Ancum JM, Tuttle CS, Koopman R, Pijnappels M, Meskers CG, Paul SK, et al. Albumin and C-reactive protein relate to functional and body composition parameters in patients admitted to geriatric rehabilitation after acute hospitalization: Findings from the RESORT cohort. Eur Geriatr Med 2022;13:623-32. https://doi.org/10.1007/s41999-022-00625-5

32. Artigas A, Wernerman J, Arroyo V, Vincent JL, Levy M. Role of albumin in diseases associated with severe systemic inflammation: Pathophysiologic and clinical evidence in sepsis and in decompensated cirrhosis. J Crit Care 2016;33:62-70. https://doi.org/10.1016/j.jcrc.2015.12.019

33. Ahmed SM, Luo L, Namani A, Wang XJ, Tang X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 2017;1863:585-97. https://doi.org/10.1016/j.bbadis.2016.11.005

34. He F, Ru X, Wen T. NRF2, a transcription factor for stress response and beyond. Int J Mol Sci 2020;21:4777. https://doi.org/10.3390/ijms21134777

35. Cuadrado A, Manda G, Hassan A, Alcaraz MJ, Barbas C, Daiber A, et al. Transcription factor NRF2 as a therapeutic target for chronic diseases: A systems medicine approach. Pharmacol Rev 2018;70:348-83. https://doi.org/10.1124/pr.117.014753

36. Sha LK, Sha W, Kuchler L, Daiber A, Giegerich AK, Weigert A, et al. Loss of Nrf2 in bone marrow-derived macrophages impairs antigen-driven CD8(+) T cell function by limiting GSH and CYS availability. Free Radic Biol Med 2015;83:77-88. https://doi.org/10.1016/j.freeradbiomed.2015.02.004

37. Osburn WO, Yates MS, Dolan PD, Chen S, Liby KT, Sporn MB, et al. Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice. Toxicol Sci 2008;104:218-27. https://doi.org/10.1093/toxsci/kfn079

38. Sorisky A, Gagnon A. Freedom of expression beyond the thyroid: The thyroid-stimulating hormone receptor in the adipocyte. OA Biochemistry 2014;2:2.

39. Diana T, Kahaly GJ. Thyroid stimulating hormone receptor antibodies in thyroid eye disease-methodology and clinical applications. Ophthalmic Plast Reconstr Surg 2018;34:S13-9. https://doi.org/10.1097/IOP.0000000000001053

40. Somma D, Kok FO, Kerrigan D, Wells CA, Carmody RJ. Defining the role of nuclear factor (NF)-κB p105 subunit in human macrophage by transcriptomic analysis of NFKB1 knockout THP1 cells. Front Immunol 2021;12:669906. https://doi.org/10.3389/fimmu.2021.669906

41. Saccani A, Schioppa T, Porta C, Biswas SK, Nebuloni M, Vago L, et al. p50 nuclear factor-κB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res 2006;66:11432-40. https://doi.org/10.1158/0008-5472.CAN-06-1867

42. Bohuslav J, Kravchenko VV, Parry GC, Erlich JH, Gerondakis S, Mackman N, et al. Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. J Clin Invest 1998;102:1645-52. https://doi.org/10.1172/JCI3877

43. Lai JJ, Chang P, Lai KP, Chen L, Chang C. The role of androgen and androgen receptor in skin-related disorders. Arch Dermatol Res 2012;304:499-510. https://doi.org/10.1007/s00403-012-1265-x

44. Lai JJ, Lai KP, Zeng W, Chuang KH, Altuwaijri S, Chang C. Androgen receptor influences on body defense system via modulation of innate and adaptive immune systems: Lessons from conditional AR knockout mice. Am J Pathol 2012;181:1504-12. https://doi.org/10.1016/j.ajpath.2012.07.008

45. Mohammad I, Starskaia I, Nagy T, Guo J, Yatkin E, Väänänen K, et al. Estrogen receptor α contributes to T cell-mediated autoimmune inflammation by promoting T cell activation and proliferation. Sci Signal 2018;11:eaap9415. https://doi.org/10.1126/scisignal.aap9415

46. Zisakis A, Katsetos CD, Vasiliou AD, Karachalios T, Li S. Expression of retinoic acid receptor (RAR) α protein in the synovial membrane from patients with osteoarthritis and rheumatoid arthritis. Int J Biomed Sci 2007;3:46-9.

47. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 2013;38:729-41. https://doi.org/10.1016/j.immuni.2013.03.003

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