Article Sidebar

Submitted
September 25, 2023
Accepted
February 12, 2024
Published
July 31, 2024
Download
PDF
Statistic
Read Counter : 139 Download : 121

Downloads

Download data is not yet available.

Main Article Content

Abstract

Background: In Central Sulawesi, Indonesia, Syzygium polyanthum leaves (SPL) have been traditionally used by society to reduce high blood pressure. However, the molecular mechanism behind this effect still remains unclear.
Objective: This study aims to explore the antihypertensive molecular mechanisms of SPL using a network pharmacology approach.
Method: Previous studies have investigated some bioactive compounds contained in SPL. Those studies identified 57 bioactive compounds, of which 31 were filtered for further analysis. Target proteins from SPL and disease were identified using GeneCards. Then, 62 selected target proteins which overlapped through Venn diagrams would be analyzed using Cytoscape software to produce compounds-target proteins’ network. Protein-protein interactions were assessed using STRING and visualized by Cytoscape. GO Function and KEGG Pathways were obtained using ShinyGo.
Results: The results of this study revealed pathways associated with hypertension through the cellular senescence pathway with target proteins mTOR, ERK (also known as MAPK), p53, CycD, and IL6. The chemical constituents associated with these target proteins are hydroxychavicol, farnesol, naphthalene, phloretin, pyrogallol, and decanal, which were identified as compounds closely related to the target protein of hypertension.
Conclusion: The bioactive compounds in SPL play a significant role in regulating hypertension by influencing various target genes, particularly those associated with cellular senescence.
Keywords: Antihypertensive, bay leaf, cellular senescence, network pharmacology, Syzygium polyanthum

Keywords

Antihypertensive bay leaf cellular senescence network pharmacology Syzygium polyanthum

Article Details

License
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish in the Jurnal Ilmiah Farmasi agree to the following terms:

  1. Authors retain copyright and grant Jurnal Ilmiah Farmasi right of first publication with the work simultaneously licensed under a Creative Commons Attribution Licence that allows others to adapt (remix, transform, and build) upon the work non-commercially with an acknowledgement of the work's authorship and initial publication in Jurnal Ilmiah Farmasi.
  2. Authors are permitted to share (copy and redistribute) the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in Jurnal Ilmiah Farmasi.
Crossref
Scopus
Google Scholar
Europe PMC

References

  1. Ahmed, W., White, I.R., Wilkinson, M., Johnson, C.F., Rattray, N., Kishore, A.K., Goodacre, R., Smith, C.J., & Fowler, S.J. (2021). Breath and Plasma Metabolomics To Assess Inflammation In Acute Stroke. Scientific Reports, 11(1), 1–14. https://doi.org/10.1038/s41598-021-01268-5
  2. Blowey, D.L. (2016). Diuretics In The Treatment of Hypertension. Pediatric Nephrology, 31(12), 2223–2233. https://doi.org/10.1007/s00467-016-3334-4
  3. Buckpitt, A., Kephalopoulos, S., Koistinen, K., Kotzias, D., Morawska, L., & Sagunski, H. (2010). Naphthalene. In: WHO Guidelines for Indoor Air Quality: Selected Pollutants, in: Geneva: World Health Organization. 4.
  4. Chamarthi, B., Williams, G.H., Ricchiuti, V., Srikumar, N., Hopkins, P.N., Luther, J.M., Jeunemaitre, X., & Thomas, A. (2011). Inflammation and Hypertension: The Interplay of Interleukin-6, Dietary Sodium, and the Renin–Angiotensin System in Humans. American Journal of Hypertension, 24(10), 1143–1148. https://doi.org/10.1038/ajh.2011.113
  5. Chang, M.C., Uang, B.J., Tsai, C.Y., Wu, H.L., Lin, B.R., Lee, C.S., Chen, Y.J., Chang, C.H., Tsai, Y.L., Kao, C.J., & Jeng, J.H. (2007). Hydroxychavicol, A Novel Betel Leaf Component, Inhibits Platelet Aggregation By Suppression of Cyclooxygenase, Thromboxane Production and Calcium Mobilization. British Journal of Pharmacology, 152, 73–82. https://doi.org/10.1038/sj.bjp.0707367
  6. Chaudhuri, J., Chowdhury, A.A., Biswas, N., Manna, A., Chatterjee, S., Mukherjee, T., Chaudhuri, U., Jaisankar, P., & Bandyopadhyay, S. (2014). Superoxide Activates mTOR-eIF4E-Bax Route To Induce Enhanced Apoptosis In Leukemic Cells. Apoptosis 19(1), 135–148. https://doi.org/10.1007/s10495-013-0904-9
  7. Cheng, W.-H., Lu, P.-J., Hsiao, M., Hsiao, C.-H., Ho, W.-Y., Cheng, P.-W., Lin, C.-T., Hong, L.-Z., & Tseng, C.-J. (2012). Renin Activates PI3K-Akt-eNOS Signalling Through The Angiotensin AT 1 and Mas Receptors To Modulate Central Blood Pressure Control In The Nucleus Tractus Solitarii. British Journal of Pharmacology, 166, 2024–2035. https://doi.org/10.1111/j.1476-5381.2012.01832.x
  8. Di Palo, K.E., Barone, N.J. (2020). Hypertension and Heart Failure: Prevention, Targets, and Treatment. Heart Failure Clinics, 16(1), 99–106. https://doi.org/10.1016/j.hfc.2019.09.001
  9. Fan, H., Lu, F., Yang, A., Dong, Y., Liu, P., & Wang, Y. (2019). A Review on the Nonpharmacological Therapy of Traditional Chinese Medicine with Antihypertensive Effects. Evidence-based Complement. Evidence-based Complementary and Alternative Medicine, 2019, 1–7. https://doi.org/10.1155/2019/1317842
  10. Ge, S.X., Jung, D., Jung, D., & Yao, R. (2020). ShinyGO: A Graphical Gene-Set Enrichment Tool For Animals and Plants. Bioinformatics, 36(8), 2628–2629. https://doi.org/10.1093/bioinformatics/btz931
  11. Harun, N.H., Rasdi, N.A., Salleh, R.M., Safuan, S., Wan Ahmad, W.A.N., & Fuad, W.E.M. (2021). Subacute Toxicity Evaluation of Methanolic Extract of Syzygium polyanthum in Rats. Tropical Life Sciences Research, 32(2), 65–81. https://doi.org/10.21315/tlsr2021.32.2.5
  12. Ismail, A., & Wan Ahmad, W.A.N. (2019). Syzygium polyanthum (Wight) Walp: A Potential Phytomedicine. Pharmacognosy Journal, 11(2), 429–438. https://doi.org/10.5530/pj.2019.11.67
  13. Ismail, A., & Wan Ahmad, W.A.N. (2017). Autonomic Receptors and Nitric‑Oxide Involvements in Mediating Vasorelaxation Effect Induced by Syzygium polyanthum Leaves Extract. Pharmacognosy Research, 9, 9–14. https://doi.org/10.4103/pr.pr
  14. Ismail, A., & Wan Ahmad, W.A.N. (2016). Vasorelaxation Effect of Syzygium polyanthum (wight) walp. Leaves Extract On Isolated Thoracic Aorta Rings of Normal and Hypertensive Rats. IIUM Medical Journal Malaysia, 15, 102. https://doi.org/10.31436/imjm.v15i1.1264
  15. Jiménez, E., & Montiel, M. (2005). Activation of MAP Kinase by Muscarinic Cholinergic Receptors Induces Cell Proliferation and Protein Synthesis in Human Breast Cancer Cells. Journal of Cellular Physiology, 204(2), 678–686. https://doi.org/10.1002/jcp.20326
  16. Kanehisa, M., Furumichi, M., Sato, Y., Ishiguro-Watanabe, M., & Tanabe, M. (2021). KEGG: Integrating Viruses and Cellular Organisms. Nucleic Acids Research, 49, 545–551. https://doi.org/10.1093/nar/gkaa970
  17. Kearney, P.M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P.K., & He, J. (2005). Global Burden of Hypertension: Analysis of Worldwide Data. Lancet, 365(9455), 217–223. https://doi.org/10.1016/s0140-6736(05)17741-1
  18. Luo, T. ting, Lu, Y., Yan, S. kai, Xiao, X., Rong, X. lu, & Guo, J. (2020). Network Pharmacology in Research of Chinese Medicine Formula: Methodology, Application and Prospective. Chinese Journal of Integrative Medicine, 26(1), 72–80. https://doi.org/10.1007/s11655-019-3064-0
  19. Luo, W., & Brouwer, C. (2013). Pathview: An R/Bioconductor Package For Pathway-Based Data Integration and Visualization. Bioinformatics, 29(14), 1830–1831. https://doi.org/10.1093/bioinformatics/btt285
  20. McCarthy, C.G., Wenceslau, C.F., Webb, R.C., & Joe, B. (2019). Novel Contributors and Mechanisms of Cellular Senescence in Hypertension-Associated Premature Vascular Aging. American Journal of Hypertension, 32(8), 709–719. https://doi.org/10.1093/ajh/hpz052
  21. Menezes, I.A.C., Barreto, C.M.N., Antoniolli, Â.R., Santos, M.R.V, & Sousa, D.P.D. (2010). Hypotensive Activity of Terpenes Found in Essential Oils. Z Naturforsch C J Biosci, 65(9-10), 562–566.
  22. Mohammed, T., Singh, M., Tiu, J.G., & Kim, A.S. (2022). Etiology and Management of Dyslipidemia in Patients With Cancer. Frontiers in Cardiovascular Medicine, 9, 1–13. https://doi.org/10.3389/fcvm.2022.892335
  23. Nakhate, K.T., Badwaik, H., Choudhary, R., Sakure, K., Agrawal, Y.O., Sharma, C., Ojha, S., & Goyal, S.N. (2022). Therapeutic Potential and Pharmaceutical Development of a Multitargeted Flavonoid Phloretin. Nutrients, 14, 1–24.
  24. Park, W.H. (2016). Pyrogallol Induces The Death of Human Pulmonary Fibroblast Cells Through ROS Increase and GSH Depletion. International Journal of Oncology, 49(2), 785–792. https://doi.org/10.3892/ijo.2016.3543
  25. Pistoia, F., Sacco, S., Degan, D., Tiseo, C., Ornello, R., & Carolei, A. (2016). Hypertension and Stroke: Epidemiological Aspects and Clinical Evaluation. High Blood Press. High Blood Pressure and Cardiovascular Prevention, 23(1), 1–10. https://doi.org/10.1007/s40292-015-0115-2
  26. Ramseyer, V.D., & Garvin, J.L. (2013). Tumor Necrosis Factor-α: Regulation of Renal Function and Blood Pressure. American Journal of Physiology - Renal Physiology, 304(10), 1231–1242. https://doi.org/10.1152/ajprenal.00557.2012
  27. Roger, I., Milara, J., Belhadj, N., & Cortijo, J. (2021). Senescence Alterations in Pulmonary Hypertension. Cells, 10(12), 1–24. https://doi.org/10.3390/cells10123456
  28. Rouzaud-Laborde, C., Lafitte, P., Balardy, L., Czosnyka, Z., & Schmidt, E.A. (2018). ICP and Antihypertensive Drugs. Acta Neurochirurgica, Supplementum, 126, 163–165. https://doi.org/10.1007/978-3-319-65798-1_34
  29. Silva, E.A.P., Carvalho, J.S., dos Santos, D.M., Oliveira, A.M.S., de Souza Araújo, A.A., Serafini, M.R., Oliveira Santos, L.A.B., Batista, M.V. d. A., Viana Santos, M.R., Siqueira Quintans, J. de S., Quintans-Júnior, L.J., & Barreto, A.S. (2021). Cardiovascular Effects of Farnesol and Its β-cyclodextrin Complex In Normotensive and Hypertensive Rats. European Journal of Pharmacology, 901, 1–11. https://doi.org/10.1016/j.ejphar.2021.174060
  30. Stannus, O., Jones, G., Cicuttini, F., Parameswaran, V., Quinn, S., Burgess, J., & Ding, C. (2010). Circulating Levels of IL-6 and TNF-α Are Associated With Knee Radiographic Osteoarthritis and Knee Cartilage Loss In Older Adults. Osteoarthritis and Cartilage, 18(11), 1441–1447. https://doi.org/10.1016/j.joca.2010.08.016
  31. Takase, H., Sugiura, T., Ohte, N., & Dohi, Y. (2015). Urinary Albumin as a Marker of Future Blood Pressure and Hypertension in the General Population. Medicine (United States), 94(6), 1–7. https://doi.org/10.1097/MD.0000000000000511
  32. Tan, R., Li, J., Peng, X., Zhu, L., Cai, L., Wang, T., Su, Y., Irani, K., & Hu, Q. (2013). GAPDH Is Critical For Superior Efficacy of Female Bone Marrow-Derived Mesenchymal Stem Cells On Pulmonary Hypertension. Cardiovascular Research, 100(1), 19–27. https://doi.org/10.1093/cvr/cvt165
  33. Ventura, H.O., & Lavie, C.J. (2019). Editorial: Epidemiology and Managing Aspects of Hypertension. Current Opinion in Cardiology, 34(4), 329–330. https://doi.org/10.1097/HCO.0000000000000631
  34. Wenzel, U.O., Bode, M., Köhl, J., & Ehmke, H. (2017). A Pathogenic Role of Complement In Arterial Hypertension and Hypertensive End Organ Damage. American Journal of Physiology - Heart and Circulatory Physiology, 312(3), 349–354. https://doi.org/10.1152/ajpheart.00759.2016
  35. Widyawati, T., Yusoff, N.A., Bello, I., Asmawi, M.Z., & Ahmad, M. (2022). Bioactivity-Guided Fractionation and Identification of Antidiabetic Compound of Syzygium polyanthum (Wight.)’s Leaf Extract in Streptozotocin-Induced Diabetic Rat Model. Molecules, 27(20), 1–15. https://doi.org/10.3390/molecules27206814