CENTELLA ASIATICA AS A MULTI-TARGET ANTISTRESS AGENT : AN IN SILICO STUDY
DOI:
https://doi.org/10.31004/jkt.v7i1.28472Keywords:
PHBS, Penyuluhan Kesehatan, PerilakuAbstract
Stres kronis yang berlebihan dapat mengganggu regulasi sumbu hipotalamus–pituitari–adrenal (HPA axis) dan berkontribusi terhadap berbagai gangguan kesehatan. Pendekatan terapi yang menargetkan satu protein seringkali kurang efektif karena kompleksitas sistem ini. Centella asiatica diketahui memiliki efek menenangkan dan mengandung senyawa bioaktif yang berpotensi sebagai agen multitarget. Penelitian ini bertujuan untuk mengevaluasi potensi asiatic acid dan madecassic acid sebagai agen antistres multitarget melalui interaksi dengan CRHR1 dan glukokortikoid reseptor (GR). Studi dilakukan secara in silico meliputi analisis ADME menggunakan SwissADME, prediksi aktivitas biologis dengan PASS, serta molecular docking menggunakan AutoDock Vina. Visualisasi interaksi dilakukan dengan Discovery Studio. Hasil docking menunjukkan bahwa kedua senyawa memiliki afinitas sedang terhadap CRHR1 (−7,7 kcal/mol), dengan asiatic acid menunjukkan interaksi yang lebih stabil dibandingkan madecassic acid. Pada GR, kedua senyawa menunjukkan afinitas yang lebih rendah (−4,5 dan −2,2 kcal/mol), meskipun asiatic acid masih mempertahankan interaksi dengan residu penting. Analisis PASS juga menunjukkan potensi aktivitas antiinflamasi dan modulasi faktor transkripsi. Asiatic acid memiliki potensi lebih tinggi sebagai agen antistres multitarget dibandingkan madecassic acid, terutama melalui interaksi dengan CRHR1 dan kemungkinan modulasi GR, meskipun diperlukan validasi eksperimental lebih lanjut.References
Alotiby, A. (2024). Immunology of Stress: A Review Article. Journal of Clinical Medicine, 13(21), 6394. https://doi.org/10.3390/jcm13216394
Bandopadhyay, S., Mandal, S., Ghorai, M., Jha, N. K., Kumar, M., Radha, Ghosh, A., Proćków, J., Pérez De La Lastra, J. M., & Dey, A. (2023). Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: A review. Journal of Cellular and Molecular Medicine, 27(5), 593–608. https://doi.org/10.1111/jcmm.17635
Battaglia, S., Fazio, C. D., Borgomaneri, S., & Avenanti, A. (2025). Cortisol Imbalance and Fear Learning in PTSD: Therapeutic Approaches to Control Abnormal Fear Responses. Current Neuropharmacology, 23(7), 835–846. https://doi.org/10.2174/1570159X23666250123142526
Bobba-Alves, N., Juster, R.-P., & Picard, M. (2022). The energetic cost of allostasis and allostatic load. Psychoneuroendocrinology, 146, 105951. https://doi.org/10.1016/j.psyneuen.2022.105951
Caruso, A., Gaetano, A., & Scaccianoce, S. (2022). Corticotropin-Releasing Hormone: Biology and Therapeutic Opportunities. Biology, 11(12), 1785. https://doi.org/10.3390/biology11121785
De Kloet, E. R., & Meijer, O. C. (2024). Glucocorticoid hormone as regulator and readout of resilience. Current Opinion in Behavioral Sciences, 59, 101439. https://doi.org/10.1016/j.cobeha.2024.101439
French, J. A., Fite, J. E., Jensen, H., Oparowski, K., Rukstalis, M. R., Fix, H., Jones, B., Maxwell, H., Pacer, M., Power, M. L., & Schulkin, J. (2007). Treatment with CRH‐1 antagonist antalarmin reduces behavioral and endocrine responses to social stressors in marmosets ( Callithrix kuhlii ). American Journal of Primatology, 69(8), 877–889. https://doi.org/10.1002/ajp.20385
Gjerstad, J. K., Lightman, S. L., & Spiga, F. (2018). Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility. Stress, 21(5), 403–416. https://doi.org/10.1080/10253890.2018.1470238
Göver, T., & Slezak, M. (2024). Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders. Pharmacological Reports, 76(6), 1333–1345. https://doi.org/10.1007/s43440-024-00654-w
Hassamal, S. (2023). Chronic stress, neuroinflammation, and depression: An overview of pathophysiological mechanisms and emerging anti-inflammatories. Frontiers in Psychiatry, 14, 1130989. https://doi.org/10.3389/fpsyt.2023.1130989
Herman, J. P., Nawreen, N., Smail, M. A., & Cotella, E. M. (2020). Brain mechanisms of HPA axis regulation: Neurocircuitry and feedback in context Richard Kvetnansky lecture. Stress, 23(6), 617–632. https://doi.org/10.1080/10253890.2020.1859475
Hernayanti, H., Lestari, S., Saryono, S., & Lestari, P. (2021). Anti-inflammatory Test of Centella Asiatica Extract on Rat Induced by Cadmium. Molekul, 16(3), 202. https://doi.org/10.20884/1.jm.2021.16.3.775
Jiang, J., Han, R., Ren, H., Yao, Y., & Jiang, W. (2025). A review of neuroprotective properties of Centella asiatica (L.) Urb. And its therapeutic effects. Annals of Medicine, 57(1), 2559122. https://doi.org/10.1080/07853890.2025.2559122
Jimeno, B., & Zimmer, C. (2022). Glucocorticoid receptor expression as an integrative measure to assess glucocorticoid plasticity and efficiency in evolutionary endocrinology: A perspective. Hormones and Behavior, 145, 105240. https://doi.org/10.1016/j.yhbeh.2022.105240
Juszczyk, G., Mikulska, J., Kasperek, K., Pietrzak, D., Mrozek, W., & Herbet, M. (2021). Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment. Antioxidants, 10(9), 1439. https://doi.org/10.3390/antiox10091439
Kageyama, K., Iwasaki, Y., & Daimon, M. (2021). Hypothalamic Regulation of Corticotropin-Releasing Factor under Stress and Stress Resilience. International Journal of Molecular Sciences, 22(22), 12242. https://doi.org/10.3390/ijms222212242
Khotimah, H., Ali, M., Sumitro, S. B., & Widodo, M. A. (2015). Decreasing α-synuclein aggregation by methanolic extract of Centella asiatica in zebrafish Parkinson’s model. Asian Pacific Journal of Tropical Biomedicine, 5(11), 948–954. https://doi.org/10.1016/j.apjtb.2015.07.024
Kim, H., Lim, T., Ha, G. E., Lee, J.-Y., Kim, J.-W., Chang, N., Kim, S. H., Kim, K. H., Lee, J., Cho, Y., Kim, B. W., Abrahamsson, A., Kim, S. H., Kim, H.-J., Park, S., Lee, S. J., Park, J., Cheong, E., Kim, B. M., & Cho, H.-S. (2023). Structure-based drug discovery of a corticotropin-releasing hormone receptor 1 antagonist using an X-ray free-electron laser. Experimental & Molecular Medicine, 55(9), 2039–2050. https://doi.org/10.1038/s12276-023-01082-1
Kivimäki, M., Bartolomucci, A., & Kawachi, I. (2023). The multiple roles of life stress in metabolic disorders. Nature Reviews Endocrinology, 19(1), 10–27. https://doi.org/10.1038/s41574-022-00746-8
Kralj, S., Jukič, M., & Bren, U. (2023). Molecular Filters in Medicinal Chemistry. Encyclopedia, 3(2), 501–511. https://doi.org/10.3390/encyclopedia3020035
Kwako, L. E., Spagnolo, P. A., Schwandt, M. L., Thorsell, A., George, D. T., Momenan, R., Rio, D. E., Huestis, M., Anizan, S., Concheiro, M., Sinha, R., & Heilig, M. (2015). The Corticotropin Releasing Hormone-1 (CRH1) Receptor Antagonist Pexacerfont in Alcohol Dependence: A Randomized Controlled Experimental Medicine Study. Neuropsychopharmacology, 40(5), 1053–1063. https://doi.org/10.1038/npp.2014.306
Ma, Y.-N., Yang, C.-J., Zhang, C.-C., Sun, Y.-X., Yao, X.-D., Liu, X., Li, X.-X., Wang, H.-L., Wang, H., Wang, T., Wang, X.-D., Zhang, C., Su, Y.-A., Li, J.-T., & Si, T.-M. (2025). Prefrontal parvalbumin interneurons mediate CRHR1-dependent early-life stress-induced cognitive deficits in adolescent male mice. Molecular Psychiatry, 30(6), 2407–2426. https://doi.org/10.1038/s41380-024-02845-6
Mahon, P. B., Zandi, P. P., Potash, J. B., Nestadt, G., & Wand, G. S. (2013). Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults. Psychopharmacology, 227(2), 231–241. https://doi.org/10.1007/s00213-012-2956-x
Murthy, T. P. K., Joshi, T., Gunnan, S., Kulkarni, N., V, P., Kumar, S. B., & Gowrishankar, B. S. (2021). In silico analysis of Phyllanthus amarus phytochemicals as potent drugs against SARS-CoV-2 main protease. Current Research in Green and Sustainable Chemistry, 4, 100159. https://doi.org/10.1016/j.crgsc.2021.100159
Odhiambo, D. O., Omosa, L. K., Njagi, E. C., Kithure, J. G., & Wekesa, E. N. (2025). In-silico pharmacokinetics ADME/Tox analysis of phytochemicals from genus Dracaena for their therapeutic potential. Scientific African, 29, e02796. https://doi.org/10.1016/j.sciaf.2025.e02796
Ortiz, R., Kluwe, B., Lazarus, S., Teruel, M. N., & Joseph, J. J. (2022). Cortisol and cardiometabolic disease: A target for advancing health equity. Trends in Endocrinology & Metabolism, 33(11), 786–797. https://doi.org/10.1016/j.tem.2022.08.002
Pagán-Busigó, J. E., López-Carrasquillo, J., Appleyard, C. B., & Torres-Reverón, A. (2022). Beyond depression and anxiety; a systematic review about the role of corticotropin-releasing hormone antagonists in diseases of the pelvic and abdominal organs. PLOS ONE, 17(3), e0264909. https://doi.org/10.1371/journal.pone.0264909
Paust, H.-J., Loeper, S., Else, T., Bamberger, A.-M., Papadopoulos, G., Pankoke, D., Saeger, W., & Bamberger, C. (2006). Expression of the Glucocorticoid Receptor in the Human Adrenal Cortex. Experimental and Clinical Endocrinology & Diabetes, 114(01), 6–10. https://doi.org/10.1055/s-2005-873007
Rasiah, N. P., Loewen, S. P., & Bains, J. S. (2023). Windows into stress: A glimpse at emerging roles for CRHPVN neurons. Physiological Reviews, 103(2), 1667–1691. https://doi.org/10.1152/physrev.00056.2021
Regazzo, D., Mondin, A., Scaroni, C., Occhi, G., & Barbot, M. (2022). The Role of Glucocorticoid Receptor in the Pathophysiology of Pituitary Corticotroph Adenomas. International Journal of Molecular Sciences, 23(12), 6469. https://doi.org/10.3390/ijms23126469
Ritter, P., Salman, R., Ryabushkina, Y., & Bondar, N. (2025). Chronic Stress Segregates Mice into Distinct Behavioral Phenotypes Based on Glucocorticoid Sensitivity. International Journal of Molecular Sciences, 26(23), 11436. https://doi.org/10.3390/ijms262311436
Sheng, J. A., Bales, N. J., Myers, S. A., Bautista, A. I., Roueinfar, M., Hale, T. M., & Handa, R. J. (2021). The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions. Frontiers in Behavioral Neuroscience, 14, 601939. https://doi.org/10.3389/fnbeh.2020.601939
Su, C., Huang, T., Zhang, M., Zhang, Y., Zeng, Y., & Chen, X. (2025). Glucocorticoid receptor signaling in the brain and its involvement in cognitive function. Neural Regeneration Research, 20(9), 2520–2537. https://doi.org/10.4103/NRR.NRR-D-24-00355
Sun, B., Wu, L., Wu, Y., Zhang, C., Qin, L., Hayashi, M., Kudo, M., Gao, M., & Liu, T. (2020). Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review. Frontiers in Pharmacology, 11, 568032. https://doi.org/10.3389/fphar.2020.568032
Wekesa, E. N., Kimani, N. M., Kituyi, S. N., Omosa, L. K., & Santos, C. B. R. (2023). Therapeutic potential of the genus Zanthoxylum phytochemicals: A theoretical ADME/Tox analysis. South African Journal of Botany, 162, 129–141. https://doi.org/10.1016/j.sajb.2023.09.009
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Dheka Sapti Iskandar, Putri Kusuma Pandin, , I Gusti Ngurah Agung Wiwekananda
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work’s authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
