Exploration of Belitung Taro Stems (Xanthosoma sagittifolium) as an Antidiabetic Candidate: An In Silico and In Vitro Approach
DOI:
https://doi.org/10.22437/chp.v10i1.48655Kata Kunci:
Diabetes Mellitus, In silico, In vitro, Xanthosoma sagittifoliumAbstrak
Diabetes mellitus is a global metabolic disorder characterized by chronic hyperglycemia. While conventional oral antidiabetics are effective, their long-term use is associated with adverse side effects, necessitating the search for safer alternatives from natural sources. Belitung taro (Xanthosoma sagittifolium) is a locally abundant tuber crop in Indonesia, but its stems are typically discarded as agricultural by-products despite their potential bioactive content. This study evaluated the antidiabetic potential of X. sagittifolium stem extract by investigating its α-amylase inhibitory activity through an integrative in silico and in vitro approach. In silico screening was performed on eight secondary metabolites from the CMAUP database, filtered based on Lipinski's Rule of Five and ADMET profiles using the pkCSM server. The lead compound, NPC141921, was docked into human pancreatic α-amylase (PDB ID: 2QV4) using AutoDock, validated by redocking acarbose. The ethanol extract was subjected to phytochemical screening and tested for α-amylase inhibition using the iodine-starch assay. NPC141921 showed a binding free energy of -6.13 kcal/mol, comparable to acarbose (-6.66 kcal/mol), forming stable hydrogen bonds with catalytic residues (ASP197, GLU233, ASP300) and substrate-binding residues (ARG195, HIS305). Phytochemical screening confirmed flavonoids, tannins, saponins, and steroids, supporting the in silico predictions. In vitro assays revealed an IC₅₀ of 5028 ppm for the stem extract versus 1953 ppm for acarbose. Although the crude extract showed lower potency due to matrix dilution effects, the findings confirm that X. sagittifolium stems contain bioactive metabolites capable of α-amylase inhibition, highlighting their potential as a natural ingredient for hyperglycemia management.
Referensi
[1] Nusantoro YR, Fadlan A. Analisis Sifat Mirip Obat, Prediksi ADMET, dan Penambatan Molekular Isatinil-2-Aminobenzoilhidrazon dan kompleks logam transisi Co(II), Ni(II), Cu(II), Zn(II) Terhadap BCL2-XL. Akta Kimia Indonesia 2020;5:114–26. https://doi.org/10.12962/j25493736.v5i2.7881.
[2] Naufa F, Mutiah R, Indrawijaya YYA. Studi in Silico Potensi Senyawa Katekin Teh Hijau (Camellia sinensis) sebagai Antivirus SARS CoV-2 terhadap Spike Glycoprotein (6LZG) dan Main Protease (5R7Y). JFood PharmSci 2022;10:584–96. https://doi.org/10.22146/jfps.3580.
[3] Inayah I, Aini FN, Hadisoebroto G. Studi In Silico Senyawa dari Herba Sambiloto (Andrographis paniculata) terhadap Protein Dihydrofolate Reductase (4KM2) pada Mycobacterium tuberculosis. Jurnal Sabdariffarma 2024;12:32–50. https://doi.org/10.53675/jsfar.v12i1.1317.
[4] Krihariyani D, Sasongkowati R, Haryanto E. Studi In Silico Sifat Farmakokinetik, Toksisitas, dan Aktivitas Imunomodulator Brazilein Kayu Secang Terhadap Enzim 3-Chymotrypsin-Like Cysteine Protease Coronavirus. Journal of Indonesian Medical Laboratory and Science 2020;1:76–90. https://doi.org/10.53699/joimedlabs.v1i1.1.
[5] Chaniad P, Mungthin M, Payaka A, Viriyavejakul P, Punsawad C. Antimalarial properties and molecular docking analysis of compounds from Dioscorea bulbifera L. as new antimalarial agent candidates. BMC Complement Med Ther 2021;21. https://doi.org/10.1186/s12906-021-03317-y.
[6] BPOM RI. Peraturan Badan Pengawas Obat dan Makanan Nomor 10 Tahun 2022 Tentang Pedoman Uji Toksisitas Praklinik Secara In Vivo. Indonesia: 2022.
[7] Shivanika, C., Deepak Kumar, S., Ragunathan, V., Tiwari, P., Sumitha, A., & Brindha Devi, P. (2022). Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. Journal of Biomolecular Structure and Dynamics, 40(2), 585–611. https://doi.org/10.1080/07391102.2020.1815584
[8] Wada E, Feyissa T, Tesfaye K. Proximate, Mineral and Antinutrient Contents of Cocoyam (Xanthosoma sagittifolium (L.) Schott) from Ethiopia. International Journal of Food Sciences, 2019;2019:8965476. https://doi.org/10.1155/2019/8965476.
[9] Salehi B, Ata A, Kumar NVA, Sharopov F, Ramírez-Alarcón K, Ruiz-Ortega A, et al. Antidiabetic potential of medicinal plants and their active components. Biomolecules 2019;9:1–121. https://doi.org/10.3390/biom9100551.
[10] Kaur S, Gadpayale D, Kumari A, Kaur G, Kumar A, Seem K, et al. Antidiabetic potential of underutilized crops: Nutritional, phytochemical insights, and prospects for diabetes management. Applied Food Research 2025;5:101127. https://doi.org/10.1016/J.AFRES.2025.101127.
[11] Uti DE, Atangwho IJ, Alum EU, Egba SI, Ugwu OPC, Ikechukwu GC. Natural Antidiabetic Agents: Current Evidence and Development Pathways from Medicinal Plants to Clinical use. Natural Product Communication. 2025;20. https://doi.org/10.1177/1934578X251323393.
[12] Kustanti IH, Pudjirahaju A, Sulistiastutik, Puspita T. Subtitusi Pasta Talas Belitung (Xanthosoma Sagittifolium (L.) Schott), Tepung Tempe Kedelai Dan Tepung Tapioka Dalam Pembuatan Mie Basah Untuk Penderita Diabetes Melitus. Jurnal Agroteknologi, 2013:129–42.
[13] Caxito MLC, Correia RR, Gomes ACC, Justo G, Coelho MGP, Sakuragui CM, et al. In Vitro Antileukemic Activity of Xanthosoma sagittifolium (Taioba) Leaf Extract. Jurnal Evidence-Based Complementary and Alternative Medicine. 2015;2015:384267. https://doi.org/10.1155/2015/384267.
[14] De Oliveira GL, De Holanda Cavalcanti Andrade L, Morais De Oliveira AF. Xanthosoma sagittifolium and Laportea aestuans: species used to prevent osteoporosis in Brazilian traditional medicine. Pharmaceutical Biology 2012;50:930–2. https://doi.org/10.3109/13880209.2011.637054.
[15] Nishanthini A, Mohan VR. Antioxidant activites of Xanthosoma sagittifolium Schott using various in vitro assay models. Asian Pacific Journal of Tropical Biomedicine, 2012;2:S1701–6. https://doi.org/10.1016/S2221-1691(12)60481-X.
[16] Handajani NS, Harini M, Yuliningsih R, Afianatuzzahra S, Hasanah U, Widiyani T. Assay for hypoglycemic functional food of cocoyam (Xanthosoma sagittifolium (L.) Schott.) tuber. IOP Conference Series: Materials Science and Engineering 2018;333:012074. https://doi.org/10.1088/1757-899X/333/1/012074.
[17] Nursamsiar, Mangande MM, Awaluddin A, Nur S, Asnawi A. In Silico Study of Aglycon Curculigoside A and Its Derivatives as α-Amilase Inhibitors. Indonesian Journal of Pharmaceutical Science and Technology Journal Homepage 2020;7:29–37. https://doi.org/10.24198/ijpst.v7i1.23062.
[18] Syahputra R, Utami D, Widyaningsih W. Studi Docking Molekuler Aktivitas Penghambatan Enzim Tirosinase Ubi Jalar (Ipomoea batatas L. Lam) Molecular Docking Study of Tyrosinase Enzyme Inhibition Activity of Sweet Potatoes (Ipomoea batatas L. Lam). Pharmacon: Jurnal Farmasi Indonesia. 2022;19:21–34. https://doi.org/10.23917/pharmacon.v19i1.18295.
[19] Ergina, Nuryanti S, Pursitasari D. Uji Kualitatif Senyawa Metabolit Sekunder Pada Daun Palado ( Agave angustifolia ) yang Diesktraksi Dengan Pelarut Air dan Metanol. Jurnal Akademika Kimia. 2014;3:165–72.
[20] Aziz Dwinuari R, Supriyanto S, Zukhruf Wakhidatul Kiromah N, Mahe Saputra A, Aji Pratama D. In Silico Study of the Potential of Belimbing Wuluh (Averrhoa bilimbi) for the Treatment of Type 2 Diabetes Mellitus. Chempublish Journal 2024;8:51–64. https://doi.org/10.22437/chp.v8i2.36624.
[21] Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry. 2015;58:4066–72. https://doi.org/10.1021/ACS.JMEDCHEM.5B00104.
[22] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 1997;23:3–25. https://doi.org/10.1016/S0169-409X(96)00423-1.
[23] Ugbe FA, Shallangwa GA, Uzairu A, Abdulkadir I. Molecular Docking Investigation, Pharmacokinetic Analysis, and Molecular Dynamic Simulation of Some Benzoxaborole-Benzimidazole Hybrids: An Approach to Identifying Superior Onchocerca Inhibitors. Borneo Journal of Pharmacy 2023;6:58–78. https://doi.org/10.33084/BJOP.V6I1.3876.
[24] Muharrami LK, Santoso M, Fatmawati S. Chemical profiles, in silico pharmacokinetic and toxicity prediction of bioactive compounds from Boesenbergia rotunda. Case Studies in Chemical and Environmental Engineering 2024;10:100992. https://doi.org/10.1016/J.CSCEE.2024.100992.
[25] Muharrami LK, Santoso M, Fatmawati S. Chemical profiles, in silico pharmacokinetic and toxicity prediction of bioactive compounds from Boesenbergia rotunda. Case Studies in Chemical and Environmental Engineering, 2024;10:100992. https://doi.org/10.1016/J.CSCEE.2024.100992.
[26] Haryati NA, Saleh C, Erwin. Uji Toksisitas Dan Aktivitas Antibakteri Ekstrak Daun Merah Tanaman Pucuk Merah (Syzygium myrtifolium Walp.) Terhadap Bakteri Staphylococcus aureus Dan Escherichia coli. Jurnal Kimia Mulawarman 2015;13.
[27] Salmia. Analisis Kadar Flavonoid Total Ekstrak Kulit Batang Kedondong Bangkok (Spondias dulcis) dengan Metode Spektrofotometro UV-VIS. Universitas Islam Negeri Alauddin Makassar, 2016.
[28] Halimu RB, Sulistijowati R, Mile L. Identifikasi Kandungan Tanin pada Sonneratia Alba. Jurnal Ilmiah Perikanan dan Kelautan, 2017;5:93–7. https://doi.org/10.37905/.v5i4.5291.
[29] Yuliyanti M, Husada VMS, Fahrudi HAA, Setyowati WAE. Quality and Detergency Optimization, Liquid Detergent Preparation, Mahogany Seed Extract (Swietenia mahagoni). JKPK (Jurnal Kimia Dan Pendidikan Kimia), 2019;4:65–76. https://doi.org/10.20961/jkpk.v4i2.32750.
[30] Khafid A, Dwijunianto Wiraputra M, Christyaji Putra A, Khoirunnisa N, Awalia Kirana Putri A, Widodo Agung Suedy S, et al. Uji Kualitatif Metabolit Sekunder pada Beberapa Tanaman yang Berkhasiat sebagai Obat Tradisional. Buletin Anatomi dan Fisiologi, 2023;8:61–70. https://doi.org/doi.org/10.14710/baf.8.1.2023.61-70.
[31] Lallo S, Mirwan M, Palino A, Nursamsiar N, Hardianti B. Aktifitas Ekstrak Jahe Merah Dalam Menurunkan Asam Urat Pada Kelinci Serta Isolasi Dan Identifikasi Senyawa Bioaktifnya. Jurnal Fitofarmaka Indonesia, 2018;5:271–8. https://doi.org/10.33096/jffi.v5i1.319.
[32] A’yun Q, Laily AN. Analisis Fitokimia Daun Pepaya (Carica papaya L.) The Phytochemical Analysis of Papaya Leaf (Carica papaya L.) at The Research Center of Various Bean and Tuber Crops Kendalpayak, Malang. Seminar Nasional Konversi dan Pemanfaatan Sumber Daya Alam, 2015 2015:1341–137.
[33] Nurpatria MA, Muhtadi. Identifikasi Senyawa Kimia Dan Uji Aktivitas Inhibisi Enzim Α-Amilase Ekstrak Etanol Akar Tembelekan (Lantana Camara L.). Medical Sains : Jurnal Ilmiah Kefarmasian, 2023;8:325–36. https://doi.org/10.37874/ms.v8i1.688.
[34] Ononamadu CJ, Ezeigwe OC, Owolarafe TA, Ihegboro GO, Lawal TA, Salawu K, et al. Starch-iodine assay method underestimates α-amylase inhibitory potential of antioxidative compounds and extracts. Biotechnologia, 2020;101:45–54. https://doi.org/10.5114/bta.2020.93103
[35] Jansen PCM, Premchand V. PROSEA - Plant Resources of South East Asia 1996. https://prosea.prota4u.org/view.aspx?id=3245 (accessed September 30, 2025).
[36] Fern K. Xanthosoma sagittifolium - Useful Tropical Plants 2014. https://tropical.theferns.info/viewtropical.php?id=Xanthosoma+sagittifolium&redir=Xanthosoma+nigrum (accessed September 30, 2025).
[37] Schott, H.W. Endlicher. S.L. Xanthosoma sagittifolium (L.) Schott 1832;19. https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:269329-2 (accessed September 30, 2025).
[38] Faisal M, Hossain AI, Rahman S, Jahan R, Rahmatullah M. A preliminary report on oral glucose tolerance and antinociceptive activity tests conducted with methanol extract of Xanthosoma violaceum aerial parts. BMC Complementary and Alternative Medicine. 2014;14. https://doi.org/10.1186/1472-6882-14-335.
[39] Zeng X, Zhang P, Wang Y, Qin C, Chen S, He W, et al. CMAUP: a database of collective molecular activities of useful plants. Nucleic Acids Research. 2018;47:D1118. https://doi.org/10.1093/NAR/GKY965.
[40] [40] Tessema FB, Asfaw TB, Tadesse MG, Gonfa YH, Bachheti RK. In Silico Studies as Support for Natural Products Research. Medinformatics 2025;2:11–21. https://doi.org/10.47852/BONVIEWMEDIN42023842.
[41] Das AP, Agarwal SM. Recent advances in the area of plant-based anti-cancer drug discovery using computational approaches. Molecular Diversity. 2023;28:1. https://doi.org/10.1007/S11030-022-10590-7.
[42] Hou D, Lin H, Feng Y, Zhou K, Li X, Yang Y, et al. CMAUP database update 2024: extended functional and association information of useful plants for biomedical research. Nucleic Acids Research. 2024;52:D1508–18. https://doi.org/10.1093/nar/gkad921.
[43] BPOM. Peraturan Kepala Badan Pengawas Obat dan Makanan Republik Indonesia Nomor 7 Tahun 2014 Tentang Pedoman Uji Toksisitas Nonklinik Secara In Vivo. Indonesia: 2014.
[44] Frimayanti N, Lukman A, Nathania L. Studi molecular docking senyawa 1,5-benzothiazepine sebagai inhibitor dengue DEN-2 NS2B/NS3 serine protease. Chempublish Journal 2021;6:54–62. https://doi.org/10.22437/chp.v6i1.12980.
[45] Klara IK, Purwono RM, Achmadi P. Analisis In Silico Senyawa Flavonoid Kayu Secang (Caesalpinia sappan L.) pada Reseptor α-Amilase Sebagai Antihiperglikemik. Acta Veterinari Indonesiana, 2023;11:210–9. https://doi.org/10.29244/avi.11.3.210-219.
[46] Pratama MRF, Poerwono H, Siswodihardjo S. Introducing a two‐dimensional graph of docking score difference vs. similarity of ligand‐receptor interactions. Indonesia Journal of Biotechnology. 2021;26:54–60. https://doi.org/10.22146/IJBIOTECH.62194.
[47] Rao SN, Head MS, Kulkarni A, LaLonde JM. Validation Studies of the Site-Directed Docking Program LibDock. Journal of Chemical Information and Modeling. 2007; 47:2159–71. https://doi.org/10.1021/CI6004299.
[48] De Almeida Jackix E, Monteiro EB, Raposo HF, Amaya-Farfán J. Cholesterol reducing and bile-acid binding properties of taioba (Xanthosoma sagittifolium) leaf in rats fed a high-fat diet. Food Research International 2013;51:886–91. https://doi.org/10.1016/J.FOODRES.2013.02.017.
[49] Neves RPP, Fernandes PA, Ramos MJ. Role of Enzyme and Active Site Conformational Dynamics in the Catalysis by α-Amylase Explored with QM/MM Molecular Dynamics. Journal of Chemical Information and Modeling. 2022;62:3638. https://doi.org/10.1021/ACS.JCIM.2C00691.
[50] Basnet S, Ghimire MP, Lamichhane TR, Adhikari R, Adhikari A. Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis. BioRxiv, 2022:2022.09.26.509544. https://doi.org/10.1101/2022.09.26.509544.
[51] Singh R, Sindhu J, Singh D, Kumar P. Key molecular scaffolds in the development of clinically viable α-amylase inhibitors. Future Medicinal Chemistry, 2025;17:347–62. https://doi.org/10.1080/17568919.2025.2453421.
[52] Dalli M, Daoudi NE, Abrigach F, Azizi SE, Bnouham M, Kim B, et al. In vitro α-amylase and hemoglobin glycation inhibitory potential of Nigella sativa essential oil, and molecular docking studies of its principal components. Frontiers in Pharmacology. 2022; 13: 1036129.https://doi.org/10.3389/FPHAR.2022.1036129.
[53] Lolok N, Ramadhan DSF, Sumiwi SA, Sahidin I, Levita J. Molecular Docking Of β-Sitosterol And Stigmasterol Isolated From Morinda Citrifolia With α-Amylase, α-Glucosidase, Dipeptidylpeptidase-Iv, And Peroxisome Proliferator-Activated Receptor-γ. Rasayan Journal of Chemistry 2022;15:20–30. https://doi.org/10.31788/RJC.2022.1516646.
[54] Wirasti, Lestari T, Isty’aroh. Penghambatan Ekstrak Daun Kremah (Alternanthera sessilis) Terhadap Enzim α-amilase secara In-Vitro. Pharmacon : Jurnal Farmasi Indonesia, 2021;18:68–74. https://doi.org/10.23917/pharmacon.v18i01.14657.
[55] Hidayah N, Pratama KJ, Raharjo D. Aktivitas Penghambatan Enzim Alfa-Amilase Ekstrak Dan Fraksidaun Nipah (Nypa Fruticans Wurmb). Jurnal Ilmiah Wahana Pendidikan, Desember 2023;2023:677–84. https://doi.org/10.5281/zenodo.10433927
[56] Nasir A, Khan M, Rehman Z, Khalil AAK, Farman S, Begum N, et al. Evaluation of alpha-amylase inhibitory, antioxidant, and antimicrobial potential and phytochemical contents of polygonum hydropiper L. Plants 2020;9:1–13. https://doi.org/10.3390/plants9070852.
[57] Turner RJ., & Charlton SJ. Assessing the Minimum Number of Data Points Required for Accurate IC 50 Determination. ASSAY and Drug Development Technologies. 2005. 3(5), 525–531. https://doi.org/10.1089/adt.2005.3.525.
[58] Miranda CTCdS., Soares SD., de Oliveira WQ, Lima AdS, Neri Numa IA, Pastore GM. Unconventional Edible Plants of the Amazon: Bioactive Compounds, Health Benefits, Challenges, and Future Trends. Foods. 2024; 13(18):2925. https://doi.org/10.3390/foods13182925
[59] Mba CJ, Agu HO. Developments on the Bioactive Compounds and Food Uses of the Tubers: Colocasia esculenta (L) Schott (Taro) and Xanthosoma sagittifolium (L) Schott (Tannia). Asian Food Science Journal 2021;20:101–12. https://doi.org/10.9734/AFSJ/2021/V20I1130380.
[60] Sanik L, Fadil Amrulloh W, Harmastuti N, Prasetiyo A, Herowati R. Analysis of Molecular Docking and Dynamics Simulation of Mahogany (Swietenia macrophylla King) Compounds Against the PLpro Enzyme SARS-COV-2. Jurnal Farmasi dan Ilmu Kefarmasian Indonesia 2023;10:347–59. https://doi.org/10.20473/JFIKI.V10I32023.347-359.
