Integrating The Network Pharmacology and Molecular Docking to Uncover The Potential Mechanism Of Rutin In Fighting Diabetes Mellitus
Keywords:
Rutin, antidiabetic, network pharmacology, molecular docking, virtual screening
Abstract
Introduction: Rutin is a flavonol glycoside that is known to have blood sugar reducing activity. However, its molecular mechanism in reducing blood sugar level remains unclear. This study was employed to elucidate the pharmacological mechanism of rutin as antidiabetic agent. Methods: Potential target of rutin was screened in relevant databases to construct a compound-target network. Network pharmacology was utilized to identify targets associated with disease, gene ontology and KEGG pathways and confirmed its potential binding affinity using Autodock 4.2 assisted by ADT interface. Result: The result highlighted mTor, PIK3R1, and NFKB1R as a potential target of Rutin through network pharmacology. This target involved in the insulin signaling pathways, insulin resistance, type 2 diabetes mellitus, B receptor signaling pathways, AGE-RAGE signaling pathway in diabetic complications and pancreatic cancer. All docking protocols were valid with RMSD value for TNF-a, NF-KB, PI3K were 0.72 Å, 0.67 Å, and 0.54 Å, respectively. The molecular docking has confirmed the potential mechanism of rutin as antidiabetic agent by stably bound with these proteins with estimated free binding energy values of -8.54 kcal/mol (NF-KB), -8.01 kcal/mol (PI3K), and -6.22 kcal/mol (TNF-a). Conclusion: The study has given insight into the molecular mechanism of rutin in the management of DM by stably bound with NF-KB, TNF-a, and PI3K. However, further laboratory experimental research is needed, particularly in vitro and in vivo assay
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References
REFERENCES
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Firzannida, Bagaskara, S., Savira, S. S., Fadnurrahim, A., & Rofida, S. (2022). Network pharmacology of black cumin (Nigella sativa L.) as a candidate of OMAI in colorectal cancer: in silico study. Indonesian Journal of Biotechnology, 27(2), 87–98. https://doi.org/10.22146/ijbiotech.70699
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Peraldi, P., Hotamisligil, G. S., Buurman, W. A., White, M. F., & Spiegelman, B. M. (1996). Tumor necrosis factor (TNF)-β inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. Journal of Biological Chemistry, 271(22), 13018–13022. https://doi.org/10.1074/jbc.271.22.13018
Prakash, T., & Ramachandra, N. B. (2022). Prioritizing Candidate Genes for Type 2 Diabetes Mellitus using Integrated Network and Pathway Analysis. Avicenna Journal of Medical Biotechnology, 14(3), 239–246. https://doi.org/https://doi.org/10.18502/ajmb.v14i3.9831
Rahman, H., Peng, S., Hu, X., Chen, C., & Rahman, R. (2020). A Network-Based Bioinformatics Approach to Identify Molecular Biomarkers for Type 2 Diabetes that Are Linked to the Progression of Neurological Diseases. International Journal of Enviromental Research and Public Health, February, 1–25. https://doi.org/10.3390/ijerph17031035
Raza, W., Guo, J., Qadir, M. I., & Bai, B. (2022). qPCR Analysis Reveals Association of Differential Expression of SRR , NFKB1 , and PDE4B Genes With Type 2 Diabetes Mellitus. 12(January), 1–14. https://doi.org/10.3389/fendo.2021.774696
Romeo, G., Liu, W. H., Asnaghi, V., Kern, T. S., & Lorenzi, M. (2002). Activation of nuclear factor-κB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes, 51(7), 2241–2248. https://doi.org/10.2337/diabetes.51.7.2241
Tsay, A., & Wang, J. (2023). The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity. august, 1–20. https://doi.org/Tsay, A., & Wang, J. (2023). The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity. 1–20.
Yarahmadi, A., Azarpira, N., & Mostafavi-pour, Z. (2022). Role of mTOR Complex 1 Signaling Pathway in the Pathogenesis of Diabetes Complications; A Mini Review. 10(3), 181–187. https://doi.org/M., Yarahmadi, A., Azarpira, N., & Mostafavi-pour, Z. (2022). Role of mTOR Complex 1 Signaling Pathway in the Pathogenesis of Diabetes Complications; A Mini Review. 10(3), 181–187. https://doi.org/10
Aghaei-Zarch, S. M. (2024). Crosstalk between MiRNAs/lncRNAs and PI3K/AKT signaling pathway in diabetes mellitus: Mechanistic and therapeutic perspectives. Non-Coding RNA Research, 9(2), 486–507. https://doi.org/10.1016/j.ncrna.2024.01.005
Al-Ishaq, R. K., Abotaleb, M., Kubatka, P., Kajo, K., & Büsselberg, D. (2019). Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules, 9(9). https://doi.org/10.3390/biom9090430
Ari Nugroho, F., Mayang Saputri Ginting, R., & Diana, N. (2015). Kadar NF- Kβ Pankreas Tikus Model Type 2 Diabetes Mellitus dengan Pemberian Tepung Susu Sapi. Indonesian Journal of Human Nutrition, 2(2), 91–100. https://doi.org/10.21776/ub.ijhn.2015.002.02.4
Chandra, J., Zhivotovsky, B., Zaitsev, S., Juntti-berggren, L., Berggren, P., & Orrenius, S. (2001). in Diabetes. 50(February).
Choi, S. S., Park, H. R., & Lee, K. A. (2021). A comparative study of rutin and rutin glycoside: Antioxidant activity, anti-inflammatory effect, effect on platelet aggregation and blood coagulation. Antioxidants, 10(11). https://doi.org/10.3390/antiox10111696
Firzannida, Bagaskara, S., Savira, S. S., Fadnurrahim, A., & Rofida, S. (2022). Network pharmacology of black cumin (Nigella sativa L.) as a candidate of OMAI in colorectal cancer: in silico study. Indonesian Journal of Biotechnology, 27(2), 87–98. https://doi.org/10.22146/ijbiotech.70699
Fox, M., & Mott, H. R. (2020). Class IA PI3K regulatory subunits : p110-independent roles and structures. 0(June), 1397–1417. https://doi.org/Fox, M., & Mott, H. R. (2020). Class IA PI3K regulatory subunits : p110-independent roles and structures. 0(June), 1397–1417.
Frimayanti, N., Lukman, A., & Nathania, L. (2021). Studi molecular docking senyawa 1,5-benzothiazepine sebagai inhibitor dengue DEN-2 NS2B/NS3 serine protease. Chempublish Journal, 6(1), 54–62. https://doi.org/10.22437/chp.v6i1.12980
Ghorbani, A. (2017). Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine and Pharmacotherapy, 96(August), 305–312. https://doi.org/10.1016/j.biopha.2017.10.001
Granata, S., Mercuri, S., Troise, D., & Gesualdo, L. (2023). post-transplant diabetes mellitus : a link still debated in kidney transplantation. May. https://doi.org/10.3389/fmed.2023.1168967
Han, J., Hou, J., Liu, Y., Liu, P., Zhao, T., & Wang, X. (2022). Using Network Pharmacology to Explore the Mechanism of Panax notoginseng in the Treatment of Myocardial Fibrosis. Journal of Diabetes Research, 2022. https://doi.org/10.1155/2022/8895950
Ibrahim, M. M., Khedr, M. M., Morsy, M. H., Badae, N. M., & Elatrebi, S. (2022). A comparative study of the cardioprotective effect of Metformin, Sitagliptin and Dapagliflozin on Isoprenaline induced myocardial infarction in non-diabetic rats. Bulletin of the National Research Centre, 46(1), 1–9. https://doi.org/10.1186/s42269-022-00812-1
Ihya, Z., Irfandi, R., Rijal, S., Yani, A., Arafah, M., & Rompegading, A. B. (2024). Literature Review: Network Pharmacology as a New Approach and Trend in Medicine. Universitas Puangrimaggalatung, Jl. Sultan Hasanuddin, 1(1), 1–8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300680/bin/f13-01-9780323911726.jpg
Lee, S. P. G., Chae, H., Lee, H., & Hoang, T. (2020). Glucose-lowering effect of Gryllus bimaculatus powder on streptozotocin-induced diabetes through the AKT / mTOR pathway. 8(May 2019), 402–409. https://doi.org/10.1002/fsn3.1323
Limanto, A., Simamora, A., Santoso, A. W., & Timotius, K. H. (2019). Antioxidant, α-Glucosidase Inhibitory Activity and Molecular Docking Study of Gallic Acid, Quercetin and Rutin: A Comparative Study. Molecular and Cellular Biomedical Sciences, 3(2), 67. https://doi.org/10.21705/mcbs.v3i2.60
Liu, Y., Zheng, Y., Zhou, Y., Liu, Y., Xie, M., Meng, W., & An, M. (2020). The expression and significance of mTORC1 in diabetic retinopathy. 1–7. https://doi.org/Liu, Y., Zheng, Y., Zhou, Y., Liu, Y., Xie, M., Meng, W., & An, M. (2020). The expression and significance of mTORC1 in diabetic retinopathy. 1–7.
Madkour, D., Ahmed, M., Elkirdasy, A., Orabi, S., & Mousa, A. (2024). Rutin: Chemical properties, Pharmacokinetic properties and Biological activities. Matrouh Journal of Veterinary Medicine, 4(1), 26–34. https://doi.org/10.21608/mjvm.2024.341806
Peraldi, P., Hotamisligil, G. S., Buurman, W. A., White, M. F., & Spiegelman, B. M. (1996). Tumor necrosis factor (TNF)-β inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. Journal of Biological Chemistry, 271(22), 13018–13022. https://doi.org/10.1074/jbc.271.22.13018
Prakash, T., & Ramachandra, N. B. (2022). Prioritizing Candidate Genes for Type 2 Diabetes Mellitus using Integrated Network and Pathway Analysis. Avicenna Journal of Medical Biotechnology, 14(3), 239–246. https://doi.org/https://doi.org/10.18502/ajmb.v14i3.9831
Rahman, H., Peng, S., Hu, X., Chen, C., & Rahman, R. (2020). A Network-Based Bioinformatics Approach to Identify Molecular Biomarkers for Type 2 Diabetes that Are Linked to the Progression of Neurological Diseases. International Journal of Enviromental Research and Public Health, February, 1–25. https://doi.org/10.3390/ijerph17031035
Raza, W., Guo, J., Qadir, M. I., & Bai, B. (2022). qPCR Analysis Reveals Association of Differential Expression of SRR , NFKB1 , and PDE4B Genes With Type 2 Diabetes Mellitus. 12(January), 1–14. https://doi.org/10.3389/fendo.2021.774696
Romeo, G., Liu, W. H., Asnaghi, V., Kern, T. S., & Lorenzi, M. (2002). Activation of nuclear factor-κB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes, 51(7), 2241–2248. https://doi.org/10.2337/diabetes.51.7.2241
Tsay, A., & Wang, J. (2023). The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity. august, 1–20. https://doi.org/Tsay, A., & Wang, J. (2023). The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity. 1–20.
Yarahmadi, A., Azarpira, N., & Mostafavi-pour, Z. (2022). Role of mTOR Complex 1 Signaling Pathway in the Pathogenesis of Diabetes Complications; A Mini Review. 10(3), 181–187. https://doi.org/M., Yarahmadi, A., Azarpira, N., & Mostafavi-pour, Z. (2022). Role of mTOR Complex 1 Signaling Pathway in the Pathogenesis of Diabetes Complications; A Mini Review. 10(3), 181–187. https://doi.org/10
Published
2024-08-05
How to Cite
Putri, S. A. P., Maharani, A. R. G., Luthfiana, D., Nweze, L. C., Setiawansyah, A., Susanti, G., & Doloking, H. (2024). Integrating The Network Pharmacology and Molecular Docking to Uncover The Potential Mechanism Of Rutin In Fighting Diabetes Mellitus. Ad-Dawaa’ Journal of Pharmaceutical Sciences, 7(1), 39-52. https://doi.org/10.24252/djps.v7i1.49701
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