In Silico Toxicity Prediction of Bioactive Compounds of Dioscorea alata L.


  • Sri N . N. Makiyah School of Medicine, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta; Jalan Brawijaya, Tamantirto, Kasihan, Bantul, Daerah Istimewa Yogyakarta 55183, (+62) 274 387656 hunting 146
  • Sherly Usman School of Medicine, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta; Jalan Brawijaya, Tamantirto, Kasihan, Bantul, Daerah Istimewa Yogyakarta 55183, (+62) 274 387656 hunting 146
  • Dinia R. Dwijayanti Department of Biology, Faculty of Mathematics and Natural Sciences, University of Brawijaya, Malang, Indonesia


Toxicity,, Yam,, Diosgenin,, Catechin,, ADMETSAR,, Protox.


Yam (Dioscorea alata L.) contains various compounds that are widely known to have various health benefits. This study aims to analyze the toxicity of the active compounds in D. alata L. in silico. This involves the screening of the bioactive compounds, drug-likeness screening based on the Lipinski rule of five, and toxicity prediction using ADMETSAR (ADMET) and Protox II (hepatotoxicity, immunotoxicity, mutagenicity, and cytotoxicity). The bioactive compounds in alata L were 64 obtained from the Kanava Knapsack and the USDA database. 23 of these compounds with potential as drugs include 6 flavonoids compounds (26.09%), 5 stilbenoid compounds (21.74%), 4 glycosides compounds (17.39%), 3 carboxylic acid compounds (13.04%), vitamins (8.69%), phenol, propiophenone and steroid (4.35%). Based on the results of LD-50, there were 2 non-toxic compounds: diosgenin and catechin. While other compounds were classified as having a low toxicity. There are 2 compounds predicted to have Human Hepatotoxicity activity, 14 compounds that have drug-induced liver injury activity, 2 hepatotoxicity compounds, 5 carcinogenicity compounds, 6 immunotoxicity compounds, 2 mutagenicity compounds, and 1 cytotoxicity compound. The toxicity is predicted to appear if used as a single compound. This study proved that most of the active compounds in D. alata L. possess very low toxicity with only 2 non-toxic compounds (catechin and diosgenin). However, the use of the compounds as a single compound is predicted to have some toxic activities. It is important to carry out further research to validate the toxicity of the active compounds D. alata vivo.


Makiyah SNN. Steroidal saponin isolates of Dioscorea alata L. induced B220IgE and B220IgG1 in vitro. In: 8th Annual Basic Science International Conference Convergence of Basic Sciences, Toward the World’s Sustainability Challenges. Malang; 2018.

Adomėnienė A, Venskutonis PR. Dioscorea spp.: comprehensive review of antioxidant properties and their relation to phytochemicals and health benefits. Molecules. 2022; 27(2530):1-36.

Makiyah SNN, Kita M, Setyawati I, Tasminatun S. Dioscorea alata L. tubers improve diabetes through anti-hyperglycemia, anti-inflammation, ameliorate insulin resistance and mitochondrial dysfunction. Indones Biomed J. 2022; article in press. Available in

Ismedsyah L and Simatupang M. Potential of uwi (Dioscorea alata L.) as antiosteoporosis in histopathological appearance of rat bone (Rattus norvegicus). Endless: Int J Future Stud. 2022; 5(2):13-18.

Makiyah SNN, Noor Z, Widodo, Rifa’i M, Djati MS. Ethanol extract of tubers Dioscorea alata L. as antiallergis agent on mice Balb/C induced with ovalbumin. Int J Pharm Bio Sci. 2014; 5(3):214-220.

Makiyah SNN, Djati MS, Muhaimin R, Widodo. Lymphocyte proliferation on hypersensitivity of Balb/C mice after given ethanol extract tuber of Dioscorea Alata L. In: The 3rd International Conference on Biological Science 2013 (The 3rd ICBS-2013). KnE Pub; 2015; 2(2015):107-111.

Makiyah SNN, Widodo, Rifa’i M, Djati MS. The influence of ethanol extract Dioscorea alata L. on CD4+CD62L+ and CD8+CD62L+ profile of Balb/C mice model digestive tract allergy. AIP Conference Proceedings. 2016; 1744(1):020054.

Francis P and Navarro VJ. Drug induced hepatotoxicity. StatPearls. StatPearls Publishing; 2022.

Kuna L, Bozic I, Kizivat T, Bojanic K, Mrso M, Kralj E, Smolic R, Wu GY, Smolic M. Models of drug induced liver injury (DILI) - current issues and future perspectives. Curr Drug Metab. 2018; 19(10):830-838.

Corvi R, Madia F, Guyton KZ, Kasper P, Rudel R, Colacci A, Kleinjans J, Jennings J. Moving forward in carcinogenicity assessment: Report of an EURL ECVAM/ESTIV workshop. Toxicol In Vitro. 2017; 45(3):278–286.

Gupta RC. Handbook of toxicology of chemical warfare agents. Cambridge: Academic Press; 2015.

Hsu KH, Su BH, Tu YS, Lin OA, Tseng YJ. Mutagenicity in a molecule: identification of core structural features of mutagenicity using a scaffold analysis. PLOS ONE. 2016; 11(2):1-17.

Mukherjee PK. Antiviral evaluation of herbal drugs. Quality Control and Evaluation of Herbal Drugs. Netherland: Elsevier Inc; 2019; 599-628.

Bhandari MR and Kawabata J. Bitterness and toxicity in wild yam (Dioscorea spp.) tubers of Nepal. Plant Foods for Hum Nutr. 2005; 60(3):129–135.

Webster J, Beck W, Ternai B. Toxicity and bitterness in Australian Dioscorea bulbifera L. and Dioscorea hispida Dennst. from Thailand. J Agric Food Chem. 1984; 32 (5):1087–1090.

Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, Yin M, Zeng X, Wu C, Lu A, Chen X, Hou T, Cao D. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 2021; 49(1):5–14.

Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res. 2014: 42(Web server issue):53-58

Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2018; 46:257-263.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46(1–3):3–26.

Petit J, Meurice N, Kaiser C, Maggiora G. Softening the rule of five—where to draw the line? Bioorg & Med Chem. 2012; 20(18):5343–5351.

Rahayu S, Prasetyawan S, Widyarti S, Atho’illah MF, and Ciptadi G. Computational study on the effectiveness of flavonoids from Marsilea crenata C. Presl as potent SIRT1 activators and NFκB inhibitors. Karbala Int J Mod Sci. 2022; 8(3):554-565

Akinwumi BC, Bordun KAM, Anderson HD. Biological activities of stilbenoids. Int J Mol Sci. 2018; 19(3):792-816.

Maag H. Prodrugs of carboxylic acids [Internet]. Prodrugs. New York: Springer; 2007; 703–729p.

Abeyrathne EDNS, Nam K, Huang X, Ahn DU. Plant- and animal-based antioxidants’structure, efficacy, mechanisms, and applications: a review. Antioxidants (Basel). 2022; 11(5):1025- 1042.

National Center for Biotechnology Information. PubChem Compound Summary for CID 5280960, Naringenin chalcone. 2022.

Jasemi SV, Khazaei H, Fakhri S, Mohammadi-Noori E, and Farzaei MH. Naringenin improves ovalbumin-induced allergic asthma in rats through antioxidant and anti-inflammatory effects. Evi-Based Comp and Altrn Med. 2022; 2022(9110798):1-10

Chen Y, Tang Y-M, Yu SL, Han Y-W, Kou J-P, Liu B-L, Yu B- Y. Advances in the pharmacological activities and mechanisms of diosgenin. Chin J Nat Med. 2015; 13(8):578–87.

Shahrajabian MH, Sun W, Marmitt DJ, Cheng Q. Diosgenin and galactomannans, natural products in the pharmaceutical sciences. Clin Phytosci. 2021; 7(50):1-7.

Sova M. Antioxidant and antimicrobial activities of cinnamic acid derivates. Mini-Rev Med Chem. 2012; 12(8):749-767.

Parvizi F, Yaghmaei P, Ali S, Rohani H, Mard SA. Hepatoprotective properties of p-coumaric acid in a rat model of ischemia-reperfusion. Avicenna J Phytomed. 2020; 10(6):633- 640.

Leung K, Quezada M, Chen Z, Kanel G, Kaplowitz N. Niacin- Induced Anicteric Microvesicular Steatotic Acute Liver Failure. Hepatol Commun. 2018; 2(11):1293-1298.

Zduńska K, Dana A, Kolodziejczak A, Rotsztejn H. Antioxidant Properties of Ferulic Acid and Its Possible Application. Skin Pharma and Phys. 2018; 31(6):332–336.

EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). Scientific Opinion on the safety and efficacy of naringin when used as a sensory additive for all animal species. EFSA J. 2011; 9(11):6-10

Pertami SB, Arifah SN, Atho’illah MF, and Budiono B. Active compounds from Polyscias scutellaria stimulate breast milk production: in silico study on serotonergic 5-HT2A receptors and prolactin receptors. Trop J Nat Prod Res. 2021; 5(7):1223-1229

Cai B, Zhang Y, Wang Z, Xu D, Jia Y, Guan Y, Liao A, Liu G, Chun CJ, Li J. Therapeutic potential of diosgenin and its major derivatives against neurological diseases: recent advances. Oxid Med and Cell Longev. 2020; 2020(3153082):1-16.




How to Cite

. N. Makiyah, S. N., Usman, S., & R. Dwijayanti, D. (2022). In Silico Toxicity Prediction of Bioactive Compounds of Dioscorea alata L.: Tropical Journal of Natural Product Research (TJNPR), 6(10), 1587–1596. Retrieved from