Network Pharmacology Approach to Understanding the Antidiabetic Effects of Pineapple Peel Hexane Extract

Authors

  • Christa Hana Angle Pendong Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, Indonesia
  • Elly Juliana Suoth Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, Indonesia
  • Fatimawali Fatimawali Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, Indonesia
  • Trina Ekawati Tallei Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, Indonesia; Department of Biology, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia

DOI:

https://doi.org/10.60084/mp.v2i1.162

Keywords:

Network Pharmacology, Pineapple peel, Type 2 Diabetes Melitus, MAPK1

Abstract

The increased interest in exploring alternative treatments for type 2 diabetes mellitus is accompanied by a rise in the prevalence of type 2 diabetes mellitus. Pineapple peel is one of the by-products of pineapple fruit and is known to possess potential for anti-diabetic activity. In this study, the n-hexane extract of pineapple peel was analyzed using network pharmacology methods to ascertain its potential in treating type 2 diabetes mellitus. The GC-MS analysis of the n-hexane extract of pineapple peel revealed the presence of 42 compounds, with 8 of them considered safe as they met the Lipinski Rule of Five criteria for drug-likeness and were classified as safe with toxicity levels in classes IV and V. The pineapple peel extract targeted 55 proteins related to type 2 diabetes mellitus (DMT2), potentially affecting DMT2 through the AGE-RAGE pathway in diabetes complications and insulin resistance. Network pharmacology analysis identified five genes targeted by pineapple peel, namely MAPK1, JAK2, MAPK8, PRKCD, and PPARA. Among these genes, MAPK1 exhibited a higher overall score than the others. Apart from its role in diabetes, MAPK1 is also implicated in cancer.

Downloads

Download data is not yet available.

References

  1. Tan, S. Y., Mei Wong, J. L., Sim, Y. J., Wong, S. S., Mohamed Elhassan, S. A., Tan, S. H., Ling Lim, G. P., Rong Tay, N. W., Annan, N. C., Bhattamisra, S. K., and Candasamy, M. (2019). Type 1 and 2 Diabetes Mellitus: A Review on Current Treatment Approach and Gene Therapy As Potential Intervention, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Vol. 13, No. 1, 364–372. doi:10.1016/j.dsx.2018.10.008.
  2. International Diabetes Federation. (2021). IDF Diabetes Atlas (10th ed.), International Diabetes Federation.
  3. Maulana, A., Faisal, F. R., Noviandy, T. R., Rizkia, T., Idroes, G. M., Tallei, T. E., El-Shazly, M., and Idroes, R. (2023). Machine Learning Approach for Diabetes Detection Using Fine-Tuned XGBoost Algorithm, Infolitika Journal of Data Science, Vol. 1, No. 1, 1–7. doi:10.60084/ijds.v1i1.72.
  4. Selvaraj, D. J. (2018). Identification of New Antidiabetic Agents Targeting GLUT4 Protein Using In Silico Analysis, International Journal of Green Pharmacy, Vol. 12, No. 04. doi:10.22377/ijgp.v12i04.2269.
  5. Lestari, L., and Zulkarnain, Z. (2021). Diabetes Melitus: Review Etiologi, Patofisiologi, Gejala, Penyebab, Cara Pemeriksaan, Cara Pengobatan dan Cara Pencegahan, Prosiding Seminar Nasional Biologi (Vol. 7), 237–241.
  6. Hamzah, D. F. (2019). Analisis Penggunaan Obat Herbal Pasien Diabetes Mellitus Tipe Ii Di Kota Langsa, JUMANTIK (Jurnal Ilmiah Penelitian Kesehatan), Vol. 4, No. 2, 168–177.
  7. Purba, E. C. (2020). Kelor (Moringa oleifera Lam.): Pemanfaatan dan Bioaktifitas, Pro-Life, Vol. 7, No. 1, 1–12. doi:10.33541/jpvol6Iss2pp102.
  8. Abas, A. H., Tallei, T. E., Idroes, R., and Fatimawali, F. (2023). Ficus minahassae (Teijsm. & de Vriese) Miq.: A Fig Full of Health Benefits from North Sulawesi, Indonesia: A Mini Review, Malacca Pharmaceutics, Vol. 1, No. 1, 1–7. doi:10.60084/mp.v1i1.24.
  9. Hopkins, A. L. (2007). Network Pharmacology, Nature Biotechnology, Vol. 25, No. 10, 1110–1111. doi:10.1038/nbt1007-1110.
  10. Syahruni, R., Umar, A. H., Rahman, H. N., and Kusuma, W. A. (2023). Exploration of Annona muricata (Annonaceae) in the Treatment of Hyperlipidemia through Network Pharmacology and Molecular Docking, Sains Malaysiana, Vol. 52, No. 3, 899–939. doi:10.17576/jsm-2023-5203-17.
  11. Tang, Y., Su, H., Wang, H., Lu, F., Nie, K., Wang, Z., Huang, W., and Dong, H. (2021). The Effect and Mechanism of Jiao-Tai-Wan in the Treatment of Diabetes Mellitus with Depression Based on Network Pharmacology and Experimental Analysis, Molecular Medicine, Vol. 27, No. 1, 154. doi:10.1186/s10020-021-00414-z.
  12. Firzannida, F., Bagaskara, S., Savira, S. S., Fadnurrahim, A., and 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, Vol. 27, No. 2, 87. doi:10.22146/ijbiotech.70699.
  13. Raihan, A., Illahi, A. K., Rokhimah, S., Elisa, T. P. P., and Maliza, R. (2023). Identification of Bioactive Solutions of Corn Silk (Zea mays L.) Extract and Biological Activity Test By Bioinformatics, Jurnal Biologi Tropis, Vol. 23, No. 1, 245–250. doi:10.29303/jbt.v23i1.5846.
  14. Fatimawali, Tallei, T. E., Kepel, B. J., Bodhi, W., Manampiring, A. E., and Nainu, F. (2023). Molecular Insight into the Pharmacological Potential of Clerodendrum minahassae Leaf Extract for Type-2 Diabetes Management Using the Network Pharmacology Approach, Medicina, Vol. 59, No. 11, 1899. doi:10.3390/medicina59111899.
  15. Tania, A. D., Kalalo, M. J., Kepel, B. J., Niode, N. J., Kusumawaty, D., and Idroes, R. (2022). Evaluation of the Potential for Immunomodulatory and Anti-inflammatory Properties of Phytoconstituents Derived from Pineapple [Ananas comosus (L.) Merr.] Peel Extract Using an In Silico Approach, Philippine Journal of Science, Vol. 151, No. 1, 397–410.
  16. Apolinário, P. P., Zanchetta, F. C., Breder, J. S. C., Adams, G., Consonni, S. R., Gillis, R., Saad, M. J. A., and Lima, M. H. M. (2023). Anti-Inflammatory, Procollagen, and Wound Repair Properties of Topical Insulin Gel, Brazilian Journal of Medical and Biological Research, Vol. 56. doi:10.1590/1414-431x2023e12640.
  17. Sireesh, D., Dhamodharan, U., Ezhilarasi, K., Vijay, V., and Ramkumar, K. M. (2018). Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent onset Type 2 Diabetes Mellitus, Scientific Reports, Vol. 8, No. 1, 5126. doi:10.1038/s41598-018-22913-6.
  18. Harkin, C., Cobice, D., Watt, J., Kurth, M. J., Brockbank, S., Bolton, S., Johnston, F., Strzelecka, A., Lamont, J. V., Moore, T., Fitzgerald, P., and Ruddock, M. W. (2023). Analysis of Reactive Aldehydes in Urine and Plasma of Type-2 Diabetes Mellitus Patients through Liquid Chromatography-Mass Spectrometry: Reactive Aldehydes As Potential Markers of Diabetic Nephropathy, Frontiers in Nutrition, Vol. 9. doi:10.3389/fnut.2022.997015.
  19. Tanase, D. M., Gosav, E. M., Costea, C. F., Ciocoiu, M., Lacatusu, C. M., Maranduca, M. A., Ouatu, A., and Floria, M. (2020). The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD), Journal of Diabetes Research, Vol. 2020, 1–16. doi:10.1155/2020/3920196.
  20. Evans, T. S., and Chen, B. (2022). Linking the Network Centrality Measures Closeness and Degree, Communications Physics, Vol. 5, No. 1, 172. doi:10.1038/s42005-022-00949-5.
  21. Zhang, J., and Luo, Y. (2017). Degree Centrality, Betweenness Centrality, and Closeness Centrality in Social Network, Proceedings of the 2017 2nd International Conference on Modelling, Simulation and Applied Mathematics (MSAM2017), Atlantis Press, Paris, France. doi:10.2991/msam-17.2017.68.
  22. Xie, T., Chen, X., Chen, W., Huang, S., Peng, X., Tian, L., Wu, X., and Huang, Y. (2021). Curcumin is a Potential Adjuvant to Alleviates Diabetic Retinal Injury via Reducing Oxidative Stress and Maintaining Nrf2 Pathway Homeostasis, Frontiers in Pharmacology, Vol. 12. doi:10.3389/fphar.2021.796565.
  23. Tallei, T. E., Fatimawali, Adam, A. A., Ekatanti, D., Celik, I., Fatriani, R., Nainu, F., Kusuma, W. A., Rabaan, A. A., and Idroes, R. (2024). Molecular Insights into the Anti-Inflammatory Activity of Fermented Pineapple Juice Using Multimodal Computational Studies, Archiv Der Pharmazie, Vol. 357, No. 1. doi:10.1002/ardp.202300422.
  24. Sukmanadi, M., Sudjarwo, S. A., and Effendi, M. H. (2020). Molecular Mechanism of Capsaicin from (Capsicum Annuum L.) on Expression of MAPK1 and AKT1 Protein as Candidate of Anticancer Drugs: In silico Study, Pharmacognosy Journal, Vol. 12, No. 4, 916–919. doi:10.5530/pj.2020.12.130.
  25. Gurzov, E. N., Stanley, W. J., Pappas, E. G., Thomas, H. E., and Gough, D. J. (2016). The Pathway in Obesity and Diabetes, The FEBS Journal, Vol. 283, No. 16, 3002–3015. doi:10.1111/febs.13709.
  26. Hayashi, Y., Toyomasu, Y., Saravanaperumal, S. A., Bardsley, M. R., Smestad, J. A., Lorincz, A., Eisenman, S. T., Cipriani, G., Nelson Holte, M. H., Al Khazal, F. J., Syed, S. A., Gajdos, G. B., Choi, K. M., Stoltz, G. J., Miller, K. E., Kendrick, M. L., Rubin, B. P., Gibbons, S. J., Bharucha, A. E., Linden, D. R., Maher, L. J., Farrugia, G., and Ordog, T. (2017). Hyperglycemia Increases Interstitial Cells of Cajal via MAPK1 and MAPK3 Signaling to ETV1 and KIT, Leading to Rapid Gastric Emptying, Gastroenterology, Vol. 153, No. 2, 521-535.e20. doi:10.1053/j.gastro.2017.04.020.
  27. Ganugula, R., Nuthalapati, N. K., Dwivedi, S., Zou, D., Arora, M., Friend, R., Sheikh-Hamad, D., Basu, R., and Kumar, M. N. V. R. (2023). Nanocurcumin Combined with Insulin Alleviates Diabetic Kidney Disease through P38/P53 Signaling Axis, Journal of Controlled Release, Vol. 353, 621–633. doi:10.1016/j.jconrel.2022.12.012.
  28. Lee, D., Shin, Y., Roh, J. S., Ahn, J., Jeoong, S., Shin, S. S., and Yoon, M. (2020). Lemon Balm Extract ALS-L1023 Regulates Obesity and Improves Insulin Sensitivity via Activation of Hepatic PPARα in High-Fat Diet-Fed Obese C57BL/6J Mice, International Journal of Molecular Sciences, Vol. 21, No. 12, 4256. doi:10.3390/ijms21124256.

Downloads

Published

2024-03-29

How to Cite

Pendong, C. H. A., Suoth, E. J., Fatimawali, F., & Tallei, T. E. (2024). Network Pharmacology Approach to Understanding the Antidiabetic Effects of Pineapple Peel Hexane Extract. Malacca Pharmaceutics, 2(1), 24–32. https://doi.org/10.60084/mp.v2i1.162

Issue

Section

Article