In Silico Study of Bioactive Compounds from Acalypha indica L. Interacting with the COX-2 Receptor as Potential Anti-Inflammatory Candidates

Lisa Savitri, Kharisul Ihsan, Rochmad Krissanjaya, Elfred Rinaldo Kasimo

Abstract


Acalypha indica L. is a medicinal herb traditionally used across Asia for treating inflammation-related conditions. Although several studies report anti-inflammatory activity in its extracts, little is known about the molecular interaction of its individual phytochemicals with cyclooxygenase-2 (COX-2)—a validated therapeutic target for inflammatory diseases. This study fills this gap by performing a comprehensive in silico analysis of 20 major bioactive compounds of A. indica using molecular docking, binding interaction profiling, and ADMET predictions. Docking against the COX-2 receptor (PDB: 3LN1) using AutoDock Vina revealed that rutin (-10.4 kcal/mol), kaempferol-3-O-rutinoside (-10.1 kcal/mol), quercetin (-9.6 kcal/mol), and luteolin (-9.3 kcal/mol) demonstrated strong predicted affinity and stable interactions with key residues Arg120, Tyr355, and Tyr385, comparable to celecoxib (-10.8 kcal/mol). ADMET profiling showed that aglycone flavonoids possessed more favorable drug-likeness properties than glycosides. These results suggest that A. indica contains multiple promising lead compounds for future COX-2 inhibition studies and highlight the molecular mechanisms supporting its ethnomedicinal use as an anti-inflammatory agent.


Keywords


Acalypha indic; COX-2; molecular docking; anti-inflammatory; flavonoids

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References


Abdelhameed, R. F. A., Habib, E. S., Elgawad, A. M. A., Hassan, S. M., Fayez, S. M., Kamel, M. S., & Mohamed, T. K. (2020). Molecular docking and pharmacokinetic profiling of natural flavonoids as potential COX-2 inhibitors. Journal of Molecular Structure, 1208, 127889. https://doi.org/10.1016/j.molstruc.2020.127889

Benkovi?, E. T., Zorc, J. J., Štefani?, M., ?anadi Jureši?, G., & Mlinari?, M. (2020). Phytosterols and inflammation modulation. Nutrients, 12(4), 1131. https://doi.org/10.3390/nu12041131

Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases. International Journal of Molecular Sciences, 19(2), 70. https://doi.org/10.3390/ijms19020470

Choudhary, N., & Sekhon, B. S. (2022). Natural flavonoids as COX-2 inhibitors: Mechanistic insights from molecular docking studies. Phytomedicine Plus, 2(4), 100292. https://doi.org/10.1016/j.phyplu.2022.100292

Ekins, S., Mestres, J., & Testa, B. (2007). In silico pharmacology for drug discovery: Applications and limitations. Journal of Medicinal Chemistry, 50(25), 6547–6560. https://doi.org/10.1021/jm070562m

Gasperotti, M., Passamonti, S., Tramer, F., Masuero, D., Guella, G., Mattivi, F., & Vrhovsek, U. (2015). Flavonoid metabolism and absorption in humans: A review. Food & Function, 6(3), 756–764. https://doi.org/10.1039/C4FO00969F

Ghosh, A., Das, B., Rout, J., Paul, S., & Bera, D. (2023). Phytochemical composition and pharmacological properties of Acalypha indica: An updated review. Journal of Ethnopharmacology, 310, 116458. https://doi.org/10.1016/j.jep.2023.116458

Khan, F., Hassan, M., Khan, N., Rehman, S., & Alharbi, M. (2021). Structural insights into COX-2 interactions and inhibitor specificity. Bioorganic Chemistry, 114, 105095. https://doi.org/10.1016/j.bioorg.2021.105095

Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and scoring in virtual screening: Methods and applications. Journal of Medicinal Chemistry, 47(17), 4151–4160. https://doi.org/10.1021/jm030369b

Kurumbail, R. G., Stevens, A. M., Gierse, J. K., McDonald, J. J., Stegeman, R. A., Pak, J. Y., Pratt, W. S., Srivastava, K. K., Marnett, L. J., Seibert, K., Isakson, P. C., & Stallings, W. C. (1996). Structural basis for selective inhibition of COX-2 by anti-inflammatory agents. Nature, 384(6610), 644–648. https://doi.org/10.1038/384644a0

Lee, J., Park, J., Kim, H., Lee, S., & Kang, K. (2010). Anti-inflammatory activity of flavonoids via COX-2 and NF-?B inhibition. Archives of Pharmacal Research, 33, 1701–1707. https://doi.org/10.1007/s12272-010-1108-y

Manach, C., Scalbert, A., Morand, C., Rémésy, C., & Jiménez, L. (2005). Bioavailability of polyphenols and flavonoids in humans. American Journal of Clinical Nutrition, 81(1), 230S–242S. https://doi.org/10.1093/ajcn/81.1.230S

Mukherjee, A., Saha, S., Ghosh, S., Majumder, M., & Das, A. (2022). Natural anti-inflammatory flavonoids as COX-2 inhibitors: A comprehensive evaluation. Biomedicine & Pharmacotherapy, 148, 112718. https://doi.org/10.1016/j.biopha.2022.112718

Nissen, S. E., Yeomans, N. D., Solomon, D. H., Libby, P., Husni, M. E., Karas, R. H., Graham, D. Y., Borer, J. S., Wisniewski, L. M., Menon, V., & Barry, A. R. (2016). Cardiovascular safety of celecoxib, naproxen, or ibuprofen in arthritis patients. New England Journal of Medicine, 375(26), 2519–2529. https://doi.org/10.1056/NEJMoa1611593

Sharma, M. (2024). Ethnomedicinal applications of Acalypha indica in Southeast Asia. Journal of Ethnopharmacology, 312, 116457. https://doi.org/10.1016/j.jep.2023.116457




DOI: https://doi.org/10.14421/biomedich.2026.151.31-37

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Copyright (c) 2026 Lisa Savitri, Kharisul Ihsan, Rochmad Krissanjaya, Elfred Rinaldo Kasimo



Biology, Medicine, & Natural Product Chemistry
ISSN 2089-6514 (paper) - ISSN 2540-9328 (online)
Published by Sunan Kalijaga State Islamic University & Society for Indonesian Biodiversity.

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This work is licensed under a CC BY-NC