Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach
Heart failure is still a global health problem that demands new pharmacological treatments. The Apelin Receptor (APR), a class A (rhodopsin-like) G-Protein Coupled Receptor (GPCR), is one of the cell membrane receptors that potentially become a specific target of heart failure therapy when...
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Universitas Indonesia
2025-01-01
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| Series: | International Journal of Technology |
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| Online Access: | https://ijtech.eng.ui.ac.id/article/view/7351 |
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| author | Muhamad Rizqy Fadhillah Wawaimuli Arozal Muhammad Habiburrahman Somasundaram Arumugam Heri Wibowo Suci Widya Primadhani Aryo Tedjo Surya Dwira Nurul Gusti Khatimah |
| author_facet | Muhamad Rizqy Fadhillah Wawaimuli Arozal Muhammad Habiburrahman Somasundaram Arumugam Heri Wibowo Suci Widya Primadhani Aryo Tedjo Surya Dwira Nurul Gusti Khatimah |
| author_sort | Muhamad Rizqy Fadhillah |
| collection | DOAJ |
| description | Heart failure is still a global health problem that demands new pharmacological treatments. The Apelin Receptor (APR), a class A (rhodopsin-like) G-Protein Coupled Receptor (GPCR), is one of the cell membrane receptors that potentially become a specific target of heart failure therapy when activated. However, no clinically approved drugs target APR. Phytochemical compounds from Indonesian herbs have become readily available for discovering novel apelin agonists. This study investigates bioactive phytochemicals from ten Indonesian medicinal herbs using computer-aided drug design (CADD) to predict ligand-receptor interactions via molecular docking and bioactivity prediction through machine learning. The selected herbs include Andrographis paniculata, Centella asiatica, Zingiber officinale, Curcuma longa, Curcuma domestica, Morinda citrifolia, Guazuma ulmifolia, Orthosiphon stamineus, Moringa oleifera, and Garcinia mangostana. Their pharmacokinetic and physicochemical profiles were also assessed using web-based predictions. Active metabolites were sourced from the Knapsack Database. Molecular docking using Molegro Virtual Docker assessed binding energy, with more negative MolDockScores indicating stronger interactions. Gambogic acid (-155.1 kJ/mol) from Garcinia mangostana and Procyanidin B2 (-154.5 kJ/mol) from Guazuma ulmifolia exhibited stronger binding than the APR agonist, Azelaprag (-149.9 kJ/mol). This study showed that Gambogic acid, Procyanidin B1, and Procyanidin B2 may predict excellent half maximal effectivity (EC50) against apelin receptors, despite their unideal lipophilicity-ligand efficiency (LELP). Gambogic acid demonstrated favorable pharmacokinetic properties: good bioavailability, minimal blood-brain barrier penetration, no cytochrome P450 (CYP) enzyme interactions, and low toxicity. The study concluded that all five selected compounds exhibited strong interactions and bioactivity as APR agonists, supporting the need for further validation through in-vitro studies. |
| format | Article |
| id | doaj-art-23329d533c4e41499f560da6a0ae18a3 |
| institution | Kabale University |
| issn | 2086-9614 2087-2100 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Universitas Indonesia |
| record_format | Article |
| series | International Journal of Technology |
| spelling | doaj-art-23329d533c4e41499f560da6a0ae18a32025-01-31T14:13:03ZengUniversitas IndonesiaInternational Journal of Technology2086-96142087-21002025-01-0116133234710.14716/ijtech.v16i1.73517351Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico ApproachMuhamad Rizqy Fadhillah0Wawaimuli Arozal1Muhammad Habiburrahman2Somasundaram Arumugam3Heri Wibowo4Suci Widya Primadhani5Aryo Tedjo6Surya Dwira7Nurul Gusti Khatimah8Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia, 10430Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia, 10430Faculty of Medicine, Imperial College London, London, UK, SW72AZDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, 700054, IndiaIntegrated Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, indonesia, 10430Public Regional Hospital of Cileungsi, Cileungsi, Bogor, Indonesia, 16820Department of Medicinal Chemistry, Faculty of Medicine, Universitas Indonesia, 10430Department of Medicinal Chemistry, Faculty of Medicine, Universitas Indonesia, 10430Master’s Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia, 10430 Heart failure is still a global health problem that demands new pharmacological treatments. The Apelin Receptor (APR), a class A (rhodopsin-like) G-Protein Coupled Receptor (GPCR), is one of the cell membrane receptors that potentially become a specific target of heart failure therapy when activated. However, no clinically approved drugs target APR. Phytochemical compounds from Indonesian herbs have become readily available for discovering novel apelin agonists. This study investigates bioactive phytochemicals from ten Indonesian medicinal herbs using computer-aided drug design (CADD) to predict ligand-receptor interactions via molecular docking and bioactivity prediction through machine learning. The selected herbs include Andrographis paniculata, Centella asiatica, Zingiber officinale, Curcuma longa, Curcuma domestica, Morinda citrifolia, Guazuma ulmifolia, Orthosiphon stamineus, Moringa oleifera, and Garcinia mangostana. Their pharmacokinetic and physicochemical profiles were also assessed using web-based predictions. Active metabolites were sourced from the Knapsack Database. Molecular docking using Molegro Virtual Docker assessed binding energy, with more negative MolDockScores indicating stronger interactions. Gambogic acid (-155.1 kJ/mol) from Garcinia mangostana and Procyanidin B2 (-154.5 kJ/mol) from Guazuma ulmifolia exhibited stronger binding than the APR agonist, Azelaprag (-149.9 kJ/mol). This study showed that Gambogic acid, Procyanidin B1, and Procyanidin B2 may predict excellent half maximal effectivity (EC50) against apelin receptors, despite their unideal lipophilicity-ligand efficiency (LELP). Gambogic acid demonstrated favorable pharmacokinetic properties: good bioavailability, minimal blood-brain barrier penetration, no cytochrome P450 (CYP) enzyme interactions, and low toxicity. The study concluded that all five selected compounds exhibited strong interactions and bioactivity as APR agonists, supporting the need for further validation through in-vitro studies.https://ijtech.eng.ui.ac.id/article/view/7351apelin receptorapelin receptor agonistheart failureindonesia medicinal herbsin-silico |
| spellingShingle | Muhamad Rizqy Fadhillah Wawaimuli Arozal Muhammad Habiburrahman Somasundaram Arumugam Heri Wibowo Suci Widya Primadhani Aryo Tedjo Surya Dwira Nurul Gusti Khatimah Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach International Journal of Technology apelin receptor apelin receptor agonist heart failure indonesia medicinal herbs in-silico |
| title | Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach |
| title_full | Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach |
| title_fullStr | Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach |
| title_full_unstemmed | Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach |
| title_short | Phytocompounds from Indonesia Medicinal Herbs as Potential Apelin Receptor Agonist for Heart Failure Therapy: An In-silico Approach |
| title_sort | phytocompounds from indonesia medicinal herbs as potential apelin receptor agonist for heart failure therapy an in silico approach |
| topic | apelin receptor apelin receptor agonist heart failure indonesia medicinal herbs in-silico |
| url | https://ijtech.eng.ui.ac.id/article/view/7351 |
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