In Silico Study of Active Compounds in Hibiscus Flower Plant (Hibiscus rosa sinensis L.) on Alpha Glucosidase Receptor (3A4A), DPP-4 Receptor (1X70), and PPAR-γ Receptor (5Y2O) as Potential Antidiabetic
Abstract
The deficiency of insulin hormone or the body's inability to use insulin leads to uncontrolled blood glucose or sugar levels, which is the cause of diabetes mellitus. The ethanol extract of hibiscus flower plant (Hibiscus rosa sinensis L.) has the ability to reduce blood glucose, suppressing hyperglycemia that causes inflammation. This study aims to evaluate the antidiabetic activity against alpha-glucosidase receptor, DPP-4 (1X70), and PPAR-γ (5Y2O), perform physicochemical predictions, and predict the toxicity of compounds in the Hibiscus rosa sinensis L. flower in silico. Several target proteins in the body related to hyperglycemia diseases are alpha-glucosidase (3A4A), DPP-4 (1X70), and PPAR-γ (5Y2O). The SwissADME software, which uses Lipinski’s Rule of Five parameters, was used for physicochemical predictions. The online software ProTox II and pkCSM were used to predict toxicity. This software refers to LD50 and classifies toxicity classes based on GHS, Ames toxicity, skin sensitivity, and hepatotoxicity. The Molegro Virtual Docker software was used to predict the activity of the compounds. The research results show that two compounds—taraxerol acetate and β-sitosterol xyloside—do not meet Lipinski's Rule of Five parameters. Three compounds are classified in toxicity class 5, three compounds in class 4, and three compounds in class 6. The activity prediction results indicate that β-sitosterol xyloside has the lowest Rerank score compared to the original ligand of alpha-glucosidase, DPP-4, and PPAR-γ receptors, as well as compared to its comparator drug. Therefore, β-sitosterol xyloside can be recommended for further research as an antidiabetic drug candidate.
References
Ali, M., Alam, P., Singh, V., Jameel, M., & Sultana, S. (2017). Phytochemical investigations of the leaves and flowers of Hibiscus rosa-sinensis L. Indian Drugs, 54(10), 30–37. https://doi.org/10.53879/id.54.10.11189
Alya, Q. A., Antari, A. L., Prasetyo, A., & Lestari, E. S. (2020). EFEKTIVITAS EKSTRAK BUNGA SEPATU (Hibiscus Rosa Sinensis L.) SEBAGAI HERBAL POTENSIAL ANTI MIKOSIS. JKR(Jurnal Kedokteran Raflesia), 6(2), 251–256.
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(January), 1–13. https://doi.org/10.1038/srep42717
Fakih, T. M., & Dewi, M. L. (2020). Interaksi Molekuler Inhibitor Dipeptidyl Peptidase-Iv ( Dpp-Iv ) Dari Protein Susu Kambing Secara in Silico Sebagai Kandidat Antidiabetes Molecular Interactions of Dipeptidyl Peptidase-Iv ( Dpp-Iv ) Inhibitors From Protein of Goat Milk Through in Silico a. Media Farmasi, 17(1), 13–24.
Huda, M., Bustan, M. N., & Gobel, F. A. (2022). Diabetes Melitus dan Hiperkolesterol Sebagai Faktor Kematian Jemaah Haji Pada Embarkasi Sultan Hasanuddin Makassar. Journal of Muslim Community Health, 3(3), 155–161.
Kesuma, D., Siswandono, S., Purwanto, B. T., & Hardjono, S. (2018). Uji in silico Aktivitas Sitotoksik dan Toksisitas Senyawa Turunan N-(Benzoil)-N’- feniltiourea Sebagai Calon Obat Antikanker. JPSCR : Journal of Pharmaceutical Science and Clinical Research, 3(1), 1. https://doi.org/10.20961/jpscr.v3i1.16266
Kilo, A. La, Aman, L. O., Sabihi, I., & Kilo, J. La. (2019). Studi Potensi Pirazolin Tersubstitusi 1-N Dari Tiosemikarbazon Sebagai Agen Antiamuba Melalui Uji In Silico. Indo. J. Chem. Res., 7(1), 9–24.
Muttaqin, F. Z., Ismail, H., & Muhammad, H. N. (2019). Studi Molecular Docking, Molecular Dynamic, Dan Prediksi Toksisitas Senyawa Turunan Alkaloid Naftiridin Sebagai Inhibitor Protein Kasein Kinase 2-Α Pada Kanker Leukemia. Pharmacoscript, 2(1), 49–64. https://doi.org/10.36423/pharmacoscript.v2i1.241
Narko, T., Permana, B., Prasetiawati, R., Soni, D., & Khairiyah, F. (2017). Molecular docking study of bulb of bawang dayak (Eleutherine palmifolia (L) Merr) compound as anti servical cancer. Jurnal Ilmiah Farmako Bahari, 8(2), 1–14. https://journal.uniga.ac.id/index.php/JFB/article/view/643
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Supandi, Yeni, & Merdekawati, F. (2018). In silico study of pyrazolylaminoquinazoline toxicity by lazar, protox, and admet predictor. Journal of Applied Pharmaceutical Science, 8(9), 119–129. https://doi.org/10.7324/JAPS.2018.8918
Weni, M., Safithri, M., & Seno, D. S. H. (2020). Molecular Docking of Active Compounds Piper crocatum on the A-Glucosidase Enzyme as Antidiabetic. Indonesian Journal of Pharmaceutical Science and Technology, 7(2), 64. https://doi.org/10.24198/ijpst.v7i2.21120
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
