Analysis of Antidiabetic Potential of Palmitic Acid Compounds Through In Silico Activation
Abstract
Diabetes Mellitus is a condition where the body's sugar level exceeds the blood's normal limit. Type 2 Diabetes Mellitus is the most common type of diabetes and is a chronic disease caused by insulin resistance and beta-cell dysfunction, resulting in decreased insulin sensitivity. The management of diabetes Mellitus is in the form of oral hypoglycemic drugs. Still, these drugs have side effects such as gastrointestinal disturbances, nausea, vomiting, hypoglycemia, macrovascular disorders, microvascular disorders, etc. So, it is necessary to seek alternative drugs to increase insulin sensitivity to lower blood sugar levels which are safer using herbal plants. One of the suspected plants that can be an alternative medicine to reduce excess blood sugar levels is the dandang gendis plant (Clinacanthus nutans). The dandang gendis plant (Clinacanthus nutans) contains palmitic acid, which can reduce excess blood sugar levels in the blood. This study aims to determine the potential of palmitic acid compounds from the Dandang gendis plant as an in silico AMPK protein activator. Methods: Qualitative descriptive method using molecular docking in silico method to determine the affinity and interaction with palmitic acid compounds in the dandang gendis plant in activating AMPK protein. Docking between palmitic acid and AMPK produces an energy value (∆Gbind) of -5.3 kcal/mol. docking of metformin resulted in the lowest energy value (∆Gbind) of 5.1 kcal/mol. The bond produced by palmitic acid docking has a fairly strong affinity for the AMPK protein of -5.3 kcal/mol. So palmitic acid, an ingredient in the dandang gendis plant (Clinacanthus nutans) has the potential as an antidiabetic.
References
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Murugesu, S., Khatib, A., Ahmed, Q. U., Ibrahim, Z., Uzir, B. F., Benchoula, K., et al. (2019). Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos. Toxicology Reports, 6, 1148–1154. https://doi.org/10.1016/j.toxrep.2019.10.020
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Nerkar, A. G., Kudale, S. A., Joshi, P. P., & Chikhale, H. U. (2012). In silico screening, synthesis and pharmacological evaluation of novel quinazolinones as NMDA receptor inhibitors for anticonvulsant activity. International Journal of Pharmacy and Pharmaceutical Sciences, 4(3), 449–453.
Panggabean, F. K., Triastuti, E., & Yunita, E. P. (2014). Uji Aktivitas Peningkatan Sensitivitas Insulin Ekstrak Biji Jintan Hitam (Nigella sativa) melalui Pengukuran Konsentrasi Tirosin Terfosforilasi Insulin Reseptor Substrat-1 (terhadap Tikus Wistar Model Diabetes Mellitus Tipe 2). Majalah Kesehatan, 1(1), 53-59.
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Siswandono. (2015). Kimia Medisinal Jilid Satu (2nd edition). Surabaya: Universitas Airlangga.
Tian, S., Wang, J., Li, Y., Li, D., Xu, L., & Hou, T. (2015). The application of in silico drug-likeness predictions in pharmaceutical research. Advanced Drug Delivery Reviews, 86, 2-10. https://doi.org/10.1016/j.addr.2015.01.009
World Health Organization. (2016). Diabetes. https://www.who.int/diabetes/country-profiles/idn_en.pdf
Xiao, B., Sanders, M. J., Carmena, D., Bright, N. J., Haire, L. F., Underwood, E., et al. (2013). Structural basis of AMPK regulation by small molecule activators. Nature Communications, 4, 3017. https://doi.org/10.1038/ncomms4017
Alam, A., Ferdosh, S., Ghafoor, K., Hakim, A., Juraimi, A. S., Khatib, A., et al. (2016). Clinacanthus nutans: A review of the medicinal uses, pharmacology and phytochemistry. Asian Pacific Journal of Tropical Medicine, 9(4), 402–409. https://doi.org/10.1016/j.apjtm.2016.03.011
Baber, J. C., Thompson, D. C., Cross, J. B., & Humblet, C. (2009). GARD: A generally applicable replacement for RMSD. Journal of Chemical Information and Modeling, 49(8), 1889–1900. https://doi.org/10.1021/ci9001074
de Beer, S., Vermeulen, N., & Oostenbrink, C. (2010). The Role of Water Molecules in Computational Drug Design. Current Topics in Medicinal Chemistry, 10(1), 55–66. https://doi.org/10.2174/156802610790232288
Bellou, V., Belbasis, L., Tzoulaki, I., & Evangelou, E. (2018). Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS ONE, 13(3), 1–27. https://doi.org/10.1371/journal.pone.0194127
Cahyaningsih, D. T. & Muwahhid, S. L. (2021). KKN UNS COVID-19: Upaya Pencegahan COVID-19 di Dukuh Wirocanan RT 3/4, Kertonatan, Kartasura, Sukoharjo. Proceedings National Conference PKM Center, 1(1), 23-29.
Calabrese, M. F., Rajamohan, F., Harris, M. S., Caspers, N. L., Magyar, R., Withka, J. M., et al. (2014). Structural basis for AMPK activation: Natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms. Structure, 22(8), 1161–1172. https://doi.org/10.1016/j.str.2014.06.009
Carling, D. (2005). AMP-activated protein kinase: Balancing the scales. Biochimie, 87(1), 87–91. https://doi.org/10.1016/j.biochi.2004.10.017
Dewinta, N. R., Mukono, I. S., & Mustika, A. (2020). Pengaruh Pemberian Ekstrak Dandang Gendis (Clinacanthus nutans) Terhadap Kadar Glukosa Darah pada Tikus Wistar Model Diabetes Melitus. Jurnal Medik Veteriner, 3(1), 76-81. https://doi.org/10.20473/jmv.vol3.iss1.2020.76-81
Ekins, S., Mestres, J., & Testa, B. (2007). In silico Pharmacology for Drug Discovery: Applications to Targets and Beyond. British Journal of Pharmacology, 152(1), 21-37. https://doi.org/10.1038/sj.bjp.0707306
Ekins, S., Nikolsky, Y., & Nikolskaya, T. (2005). Techniques: Application of systems biology to absorption, distribution, metabolism, excretion and toxicity. Trends in Pharmacological Sciences, 26(4), 202–209. https://doi.org/10.1016/j.tips.2005.02.006
Ferdian, P. R. (2016). Potensi senyawa asam lemak rantai pendek sebagai aktivator langusung AMPK secara in silico untuk terapi sindrom metabolik. Thesis. Bogor: IPB University.
Hardie, D. G. (2008). AMPK: A key regulator of energy balance in the single cell and the whole organism. International Journal of Obesity, 32(Suppl 4), S7–S12. https://doi.org/10.1038/ijo.2008.116
Hardie, D. G. (2015). AMPK: Positive and negative regulation, and its role in whole-body energy homeostasis. Current Opinion in Cell Biology, 33, 1–7. https://doi.org/10.1016/j.ceb.2014.09.004
Imam, M. U., Ismail, M., George, A., Chinnappan, S. M., & Yusof, A. (2019). Aqueous leaf extract of Clinacanthus nutans improved metabolic indices and sorbitol-related complications in type II diabetic rats (T2D). Food Science and Nutrition, 7(4), 1482–1493. https://doi.org/10.1002/fsn3.988
Ismail, N. Z., Md Toha, Z., Muhamad, M., Kamal, N. N. M., Zain, N. N. M., & Arsad, H. (2020). Antioxidant Effects, Antiproliferative Effects, and Molecular Docking of Clinacanthus nutans Leaf Extracts. Molecules, 25(9), 2067. https://doi.org/10.3390/molecules25092067
Janani, C. & Kumari, B. D. R. (2015). PPAR gamma gene - A review’, Diabetes and Metabolic Syndrome, 9(1), 46–50. https://doi.org/10.1016/j.dsx.2014.09.015
Joshi, T., Singh, A. K., Haratipour, P., Sah, A. N., Pandey, A. K., Naseri, R., et al. (2019). Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications. Journal of Cellular Physiology, 234(10), 17212–17231. https://doi.org/10.1002/jcp.28528
Kurnia, K. A., Harimurti, S., Yung, H. K., Baraheng, A., Alimin, M. A. S., Dagang, N. S. M., et al. (2019). Understanding the effect of pH on the solubility of Gamavuton-0 in the aqueous solution: Experimental and COSMO-RS modelling. Journal of Molecular Liquids, 296, 111845. https://doi.org/10.1016/j.molliq.2019.111845
Lim, C. T., Kola, B., & Korbonits, M. (2010). AMPK as a mediator of hormonal signalling. Journal of Molecular Endocrinology, 44(2), 87–97. https://doi.org/10.1677/jme-09-0063
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advanced Drug Delivery Reviews, 64, 4-17. https://doi.org/10.1016/j.addr.2012.09.019
Müller-Wieland, D. & Kommission Labordiagnostik in der Diabetologie der Deutschen Diabetes Gesellschaft (DDG) und der Deutschen Gesellschaft für Klinische Chemie und Laboratoriumsmedizin (DGKL). (2019). Definition, Classification and Diagnosis of Diabetes Mellitus. Der Diabetologe, 15(2), 128–134. https://doi.org/10.1007/s11428-019-0460-1
Murugesu, S., Khatib, A., Ahmed, Q. U., Ibrahim, Z., Uzir, B. F., Benchoula, K., et al. (2019). Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos. Toxicology Reports, 6, 1148–1154. https://doi.org/10.1016/j.toxrep.2019.10.020
Nandipati, K. C., Subramanian, S., & Agrawal, D. K. (2017). Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance. Molecular and Cellular Biochemistry, 426, 27–45. https://doi.org/10.1007/s11010-016-2878-8
Nerkar, A. G., Kudale, S. A., Joshi, P. P., & Chikhale, H. U. (2012). In silico screening, synthesis and pharmacological evaluation of novel quinazolinones as NMDA receptor inhibitors for anticonvulsant activity. International Journal of Pharmacy and Pharmaceutical Sciences, 4(3), 449–453.
Panggabean, F. K., Triastuti, E., & Yunita, E. P. (2014). Uji Aktivitas Peningkatan Sensitivitas Insulin Ekstrak Biji Jintan Hitam (Nigella sativa) melalui Pengukuran Konsentrasi Tirosin Terfosforilasi Insulin Reseptor Substrat-1 (terhadap Tikus Wistar Model Diabetes Mellitus Tipe 2). Majalah Kesehatan, 1(1), 53-59.
Putra, R. J. S., Achmad, A., & Rachma, H. P. (2017). Kejadian Efek Samping Potensial Terapi Obat Anti Diabetes Pada Pasien Diabetes Melitus Berdasarkan Algoritme Naranjo. Pharmaceutical Journal of Indonesia, 2(2), 45–50.
Siswandono. (2015). Kimia Medisinal Jilid Satu (2nd edition). Surabaya: Universitas Airlangga.
Tian, S., Wang, J., Li, Y., Li, D., Xu, L., & Hou, T. (2015). The application of in silico drug-likeness predictions in pharmaceutical research. Advanced Drug Delivery Reviews, 86, 2-10. https://doi.org/10.1016/j.addr.2015.01.009
World Health Organization. (2016). Diabetes. https://www.who.int/diabetes/country-profiles/idn_en.pdf
Xiao, B., Sanders, M. J., Carmena, D., Bright, N. J., Haire, L. F., Underwood, E., et al. (2013). Structural basis of AMPK regulation by small molecule activators. Nature Communications, 4, 3017. https://doi.org/10.1038/ncomms4017
Published
2022-12-05
How to Cite
SALSABILA, Ardellya Elfidaa; SUSANTI, Nurlaili; ULHAQ, Zulvikar Syambani.
Analysis of Antidiabetic Potential of Palmitic Acid Compounds Through In Silico Activation.
Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR), [S.l.], v. 2, p. 21-30, dec. 2022.
ISSN 2827-7848.
Available at: <http://conferences.uin-malang.ac.id/index.php/planar/article/view/1849>. Date accessed: 23 apr. 2024.
doi: https://doi.org/10.18860/planar.v2i0.1849.
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