• ELLIN FEBRINA Department of Chemistry, Faculty of Mathematics and Natural Sciences, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
  • RYAN KHUNAM ALAMHARI Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung, 40617, Indonesia
  • RIZKY ABDULAH Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
  • KERI LESTARI Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia, Center of Excelence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jl. Dipatiukur No. 35, Bandung, 40132, Indonesia
  • JUTTI LEVITA Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia
  • UNANG SUPRATMAN Department of Chemistry, Faculty of Mathematics and Natural Sciences, Central Laboratory, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia



Acalypha indica L., Apoptosis, Caspase-3, Molecular docking, Molecular dynamics


Objective: This study investigated the structure-based molecular interactions between phytochemical constituents of Acalypha indica L. and caspase-3.

Methods: Thirty-three phytochemical constituents of A. indica were screened against caspase-3. The X-ray crystal structure of human caspase-3 was retrieved from The molecular interactions of the phytochemicals were studied using the AutoDock 4.2 software and followed by molecular dynamics (MD) simulations using the Amber18 software.

Results: From this study, 25 screened phytochemicals were found to have a better binding mode than the native ligand. Moreover, the binding stability of the top four hits evaluated by MD indicated that the hydrogen bonds in MD were quite different from the molecular docking results due to the massive receptor and ligand movement in the MD simulations. However, with the exception of stigmasterol, all ligands were able to stabilize the protein.

Conclusion: This study suggested that γ-sitosterol acetate, β-sitosterol acetate, and γ-sitosterol might be able to induce caspase-3, thereby activating apoptosis. These high-affinity compounds can bind to caspase-3 more efficiently and were able to stabilize the protein. Therefore, they have the potential to be used as lead compounds in the treatment of cancer.


Download data is not yet available.


Zahidin NS, Saidin S, Zulkifli RM, Muhamad II, Ya’akob H, Nur H. A review of Acalypha indica L. (Euphorbiaceae) as traditional medicinal plant and its therapeutic potential. J Ethnopharmacol. 2017;207:146-73. doi: 10.1016/j.jep.2017.06.019, PMID 28647509.

Savithramma N, Sulochana Ch, Rao KN. Ethnobotanical survey of plants used to treat asthma in Andhra Pradesh, India. J Ethnopharmacol. 2007;113(1):54-61. doi: 10.1016/ j.jep.2007.04.004, PMID 17606346.

Das PR, Akter S, Islam MT, Kabir MH, Haque MM, Khatun Z. A selection of medicinal plants used for treatment of diarrhea by folk medicinal practitioners of Bangladesh. Am–Eurasia J Sustain Agric. 2012;6:153-61.

Mohan C, Dinakar S, Anand T, Elayaraja R, Sathiya Priya B. Phytochemical, GC-MS analysis and antibacterial activity of a medicinal plant Acalypha indica. Int J Pharm Tech Res. 2012;4:1050-4.

Divya N, Thenmozhi S, Sureshkumar B, Selvan M. Antibacterial activity of medicinal plant against wound infected pathogens. Int J Pharm Sci Res. 2014;5:4942-7.

Saha R, Ahmed A. Phytochemical constituents and pharmacological activities of Acalyphus indica Linn: a review. Int J Pharm Sci Res. 2011;2:1900-4.

Ribeiro A, Romeiras MM, Tavares J, Faria MT. Ethnobotanical survey in Canhane village, district of Massingir, Mozambique: medicinal plants and traditional knowledge. J Ethnobiol Ethnomed. 2010;6:33. doi: 10.1186/1746-4269-6-33, PMID 21129187.

Singh AG, Kumar A, Tewari DD. An ethnobotanical survey of medicinal plants used in Terai forest of western Nepal. J Ethnobiol Ethnomed. 2012;8:19. doi: 10.1186/1746-4269-8-19, PMID 22591592.

Jayaprakasam R, Ravi T. Evaluation of anti-arthritic activity of the root extract of Acalypha indica Linn. using in vitro techniques. Int J Phytopharmacol. 2013;2:169-73.

Marwah RG, Fatope MO, Al Mahrooqi R, Varma GB, Al Abadi H. Al-Burtamani. SKS. Antioxidant capacity of some edible and wound healing plants in Oman. Food Chem 2007;101:465-70.

Govindarajan M, Jebanesan A, Reetha D, Amsath R, Pushpanathan T, Samidurai K. Antibacterial activity of Acalypha indica L. Eur Rev Med Pharmacol Sci. 2008;12(5):299-302. PMID 19024213.

Solomon RDJ, Kallidass S, Vimalan J. Isolation, identification and study of antimicrobial property of a bioactive compound in an Indian medicinal plant Acalypha indica (Indian-nettle). World J Microbiol Biotechnol. 2005;21(6-7):1231-6. doi: 10.1007/s11274-005-1479-6.

Rajasekaran S, Anandan R, Nishad K. Antihyperlipidemic activity of Acalypha indica Linn. on atherogenic diet induced hyperlipidemia. Int J Pharm Pharm Sci. 2013;5:699-701.

Rahman MA, Bachar SC, Rahmatullah M. Analgesic and antiinflammatory activity of methanolic extract of Acalypha indica Linn. Pak J Pharm Sci. 2010;23(3):256-8. PMID 20566436.

Amarnath K, Dhanabal J, Agarwal I, Seshadry S. Cytotoxicity induction by ethanolic extract of Acalypha indica loaded casein-chitosan microparticles in human prostate cancer cell line in vitro. Biomed Prev Nutr. 2014;4(3):445-50. doi: 10.1016/j.bionut.2013.03.009.

Nagendran S, Muthukumar T, Ramalingam S, Palanisamy S, Hameed SS. Influence of Acalypha indica in cell proliferation, cell cycle arrest and anticancer activity in HT-29 colon cell lines. Pharm Lett. 2015;7(9):40-52.

Sanseera D, Niwatananun W, Liawruangrath B. Antioxidant and anticancer activities from aerial parts of Acalypha indica Linn. Chiang Mai Univ J Nat Sci. 2012;11(2):157-68.

Ma YT, Chuang JI, Lin JH, Hsu F. Phenolics from acalypha indica. Int Chinese Chemical Soc. 1997;44(5):499-502. doi: 10.1002/jccs.199700075.

Nahrstedt A, Hungeling M, Petereit F. Flavonoids from Acalypha indica. Fitoterapia. 2006;77(6):484-6. doi: 10.1016/j.fitote.2006.04.007, PMID 16828241.

Ghani A. Medicinal plants of Bangladesh: chemical constituents and uses. 2nd ed. Dhaka: Asiatic Society of Bangladesh; 2003.

Balakrishnan NA, Raj JS, Kandakatla NA. In silico studies on new indazole derivatives as GSK-3 inhibitors. Int J Pharm Pharm Sci. 2015;7:295-9.

Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99-104. doi: 10.1038/sj.cdd.4400476, PMID 10200555.

McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5(4):a008656. doi: 10.1101/cshperspect.a008656, PMID 23545416.

Visualizer. ADS Version 4. 5. Softw. Vis. Anal. Protein Struct.; 2017.

Rizvi SMD, Shakil S, Haneef M. A simple click by click protocol to perform docking: AutoDock 4.2 made easy for non-bioinformaticians. Excli J. 2013;12:831-57. PMID 26648810.

Muttaqin FZ, Kharisma D, Asnawi A, Kurniawan F. Pharmacophore and molecular docking-based virtual screening of B-cell lymphoma 2 (BCL 2) inhibitor from zinc natural database as anti-small cell lung cancer. J Drug Delivery Ther. 2020;10(2):143-7. doi: 10.22270/jddt.v10i2.3923.

Nursamsiar N, Mangande M, Awaluddin A, Nur S, Asnawi A. In silico study of aglycon curculigoside A and its derivatives as α-amilase inhibitors. Indonesian J Pharm Sci Technol. 2020;7(1):29-37. doi: 10.24198/ijpst.v7i1.23062.

Lee TS, Cerutti DS, Mermelstein D, Lin C, LeGrand S, Giese TJ, Roitberg A, Case DA, Walker RC, York DM. GPU-accelerated molecular dynamics and free energy methods in Amber18: performance enhancements and new features. J Chem Inf Model. 2018;58(10):2043-50. doi: 10.1021/acs.jcim.8b00462, PMID 30199633.

Erlanson DA, Lam JW, Wiesmann C, Luong TN, Simmons RL, DeLano WL, Choong IC, Burdett MT, Flanagan WM, Lee D, Gordon EM, O’Brien T. In situ assembly of enzyme inhibitors using extended tethering. Nat Biotechnol. 2003;21(3):308-14. doi: 10.1038/nbt786, PMID 12563278.

Megantara S, Mutakin M, Halimah E, Febrina E, Levita J. Molecular interaction of the downstream executioner cysteine aspartyl proteases (caspase-3 and caspase-7) with corilagin, quercetin, rutin, kaempferol, gallic acid, and geraniin of Acalypha wilkesiana mull. Arg Rasayan J Chem. 2020;13(3):1321-9. doi: 10.31788/RJC.2020.1335766.

Jakalian A, Bush BL, Jack DB, Bayly CI. Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method. J Comput Chem. 2000;21(2):132-46. doi: 10.1002/(SICI)1096-987X(20000130)21:2<132:AID-JCC5>3.0.CO;2-P.

Sundarraj S, Thangam R, Sreevani V, Kaveri K, Gunasekaran P, Achiraman S, Kannan S. γ-sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells. J Ethnopharmacol. 2012;141(3):803-9. doi: 10.1016/j.jep.2012.03.014, PMID 22440953.

Endrini S, Rahmat A, Ismail P, Taufiq Yap YH. Cytotoxic effect of γ-sitosterol from Kejibeling (Strobilanthes crispus) and its mechanism of action towards c-myc gene expression and apoptotic pathway. Med J Indones. 2014;23(4):203-8. doi: 10.13181/mji.v23i4.1085.

Cole JC, Murray CW, Nissink JWM, Taylor RD, Taylor R. Comparing protein-ligand docking programs is difficult. Proteins. 2005;60(3):325-32. doi: 10.1002/prot.20497, PMID 15937897.



How to Cite




Original Article(s)