A New Insight Into Toxicity of Database Compounds from Ginger (Zingiber officinale) by Modelling Study

Authors

  • Neni Frimayanti Department of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Indonesia https://orcid.org/0000-0003-2369-6787
  • Mira Febrina Department of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Indonesia
  • Annisa Yuri Amalia Department of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Indonesia

DOI:

https://doi.org/10.25077/jrk.v15i1.638

Keywords:

Zingiber officinale, dengue NS2B/NS3, docking, toxicity, binding free energy

Abstract

Dengue haemorrhagic fever (DHF) is an infectious disease caused by the dengue virus. The dengue virus is transmitted through female mosquitoes, especially Aedes aegypti and Aedes albopictus. Indonesia is a dengue endemic country, and almost all provinces in Indonesia are infected with dengue. However, targeted antiviral drugs against dengue virus (DENV) are not yet available. This study aimed to determine the potential of three compounds isolated from ginger (Zingiber officinale) as dengue NS2B/NS3 inhibitors, and to predict the physicochemical properties (drug-likeness) and potential toxicity of drug candidates. Ginger isolates in the form of [8]-gingerol, [6]-paradol, shogaol were obtained from the Natural Discovery Database (NADI). Toxicity and drug-likeness predictions were performed using ProTox-II and SwissADME, and Molecular Operating Environment (MOE) 2022.0901 was used for the molecular docking process. Results: The results showed that the ginger compound (Zingiber officinale), [8]-Gingerol, [6]-Paradol, and Shogaol, had binding free energy of -7.18, -7.10 and -6.88 kcal/mol, respectively. It is indicated that three compounds had  potentiality to inhibit the NS2B/NS3 protein complex with a binding free energy that was almost equivalent to that of the positive control, panduratin A, and similar to that of the positive control, which can be seen in superimposition. In addition, three compounds isolated from ginger met the drug-likeness parameters. Based on the analysis of in silico toxicity studies, the three compounds isolated from ginger showed different levels of toxicity. Therefore, based on the safety level of oral use, the [8]-gingerol compound is safer to develop as a dengue antiviral drug, where the LD50 value of [8]-gingerol is 2.580 mg/kg with a class V toxicity level that is practically nontoxic.

References

WHO. (2011). Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. New Delhi: WHO Regional Publication SEARO.

Bhatt, S., Gething, P.W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L,. Drake, J. M., Brownstein, J. S., Hoen, A. G., Sankoh, O. (2013). The global Distribution and Burden of Dengue. Nature. 496 (7446):504–7. DOI: 10.1038/nature12060

WHO. (2011). Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. New Delhi: WHO Regional Publication SEARO

Kumaria, R. (2010). Correlation of Disease Spectrum Among Four Dengue Serotypes: a Five Years Hospital Based Study From India. Brazilian Journal of Infectious Diseases, 14 (2): 141–146.

Zimmer, J.Y., Saegerman, C., Losson, B. and Haubruge, E. (2010). Breeding Sites of Bluetongue Virus Vectors, Belgium. Emerging Infectious Diseases, 16 (3): 575–576. doi: 10.3201/eid1603.091311

Kurniati, A., Fandi, A., Sariyanti, M., Febrianti, E. and Rizqoh, D. (2021). Perbandingan Tingkat Keparahan Infeksi Sekunder Virus Dengue pada Keempat Serotipe di Indonesia: Systematic Review. Jurnal Kesehatan Andalas, 10 (1): 49. https://doi.org/10.25077/jka.v10i1.1615

Kee, L.Y., Kiat, T.S., Wahab, H.A., Yusof, R., Rahman, N.A. (2007). Non substrate Based Inhibitors of Dengue Virus Serine Protease: A Molecular Docking Approach to Study Binding Interactions between Protease and Inhibitors. Asia-Pacific Journal of Molecular Biology and Biotechnology. 15 (2): 53–59.

Wang, W.H., Urbina, A.N., Chang, M.R., Assavalapsakul, W., Lu, P.L., Chen, Y.H. and Wang, S.F. (2020). Dengue Hemorrhagic Fever – A Systemic Literature Review of Current Perspectives on Pathogenesis, Prevention and Control. Journal of Microbiology, Immunology and Infection, 53 (6): 963–978. https://doi.org/10.1016/j.jmii.2020.03.007

Chambers, T. J., Nestorowicz, A., Amberg, S. M., Rice, C.M., (1993). Mutagenesis of the Yellow Fever Virus NS2B Protein: Effects On Proteolytic Processing, NS2B-NS3 Complex Formation, and Viral Replication. J Virol. 67 (11): 6797-07. doi: 10.1128/jvi.67.11.6797-6807.1993

Sampath A, Padmanabhan R. (2009). Molecular Targets for Flavivirus Drug Discovery. Antiviral Res. 81: 6–15. doi: 10.1016/j.antiviral.2008.08.004.

Stoner,G.D. (2013). Ginger: Is it Ready for Prime Time? Cancer Prevention Research, 6 (4): 257–262. https://doi.org/10.1158/1940-6207.CAPR-13-0055

Nile, S.H. and Park, S.W. (2015). Chromatographic Analysis, Antioxidant, Anti-Inflammatory, and Xanthine Oxidase Inhibitory Activities of Ginger Extracts and its Reference Compounds. Industrial Crops and Products, 70: 238–244. https://doi.org/10.1016/j.indcrop.2015.03.033

Zhang, M., Viennois, E., Prasad, M., Zhang, Y., Wang, L., Zhang, Z., Han, M.K., Xiao, B., Xu, C., Srinivasan, S. and Merlin, D. (2016) Edible Ginger-Derived Nanoparticles: A Novel Therapeutic Approach for the Prevention and Treatment of Inflammatory Bowel Disease and Colitis-Associated Cancer. Biomaterials, 101: 321–340. DOI: 10.1016/j.biomaterials.2016.06.018

Kumar, N.V., Murthy, P.S., Manjunatha, J.R. and Bettadaiah, B.K. (2014). Synthesis and Quorum Sensing Inhibitory Activity of Key Phenolic Compounds of Ginger and Their Derivatives. Food Chemistry, 159: 451–457. DOI: 10.1016/j.foodchem.2014.03.039

Citronberg, J., Bostick, R., Ahearn, T., Turgeon, D.K., Ruffin, M.T., Djuric, Z., Sen, A., Brenner, D.E. and Zick, S.M. (2013). Effects of Ginger Supplementation on Cell-Cycle Biomarkers in the Normal-Appearing Colonic Mucosa of Patients at Increased Risk for Colorectal Cancer: Results from a Pilot, Randomized, and Controlled Trial. Cancer Prevention Research, 6(4): 271–281. DOI: 10.1158/1940-6207.CAPR-12-0327

Kaushik, S., Jangra, G., Kundu, V., Yadav, J.P., Kaushik, S. (2020). Anti-Viral Activity of Zingiber officinale (Ginger) Ingredients Against the Chikungunya Virus. Virus Dis, 31: 270–276. DOI: 10.1007/s13337-020-00584-0

Chang, J.S., Wang, K.C., Yeh, C.F., Shieh, D.E., Chiang, L.C. (2013). Fresh Ginger (Zingiber officinale) has Antiviral Activity Against Human Respiratory Syncytial Virus in Human Respiratory Tract Cell Lines. J. Ethnopharmacol, 145 (1): 146–151. DOI: 10.1016/j.jep.2012.10.043

Wang, W.H., Urbina, A.N., Chang, M.R., Assavalapsakul, W., Lu, P.L., Chen, Y.H. and Wang, S.F. (2020). Dengue Hemorrhagic Fever – A Systemic Literature Review of Current Perspectives on Pathogenesis, Prevention and Control. Journal of Microbiology, Immunology and Infection, 53(6): 963–978. https://doi.org/10.1016/j.jmii.2020.03.007

Frimayanti, N., Chee, C.F., Zain, S.M., Rahman, N.A. (2011). Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors-A Computational Approach. International Journal of Molecular Sciences, 12(2): 1089–1100. https://doi.org/10.3390/ijms12021089

Prieto, M.F.D., Arciniega, M., Medina-Franco, J.L. (2018). Molecular Docking: Current Advance and Challanges. TIP Revista Especializada En Ciencias Químico-Biológicas, 21: 65-87

Sakaeda T, Okamura N, Nagata S, Yagami T, Horinouchi M, Okumura K, Yamashita F, Hashida M. (2001). Molecular and pharmacokinetic properties of 222 commercially available oral drugs in humans. Biol Pharm Bull. 24(8):935-40. doi: 10.1248/bpb.24.935.

Daina, A., Oliver, M., Vincent, Z. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medical chemistry friendliness of small molecules. Scientific Reports. 7 (4), 1-13. doi: 10.1038/srep42717 (2017).

Siramshetty, V.B., Nickel, J., Omieczynski, C., Gohlke, B.O., Drwal, M.N. & Preissner, R. 2016. WITHDRAWN - A Resource for Withdrawn and Discontinued Drugs. Nucleic Acids Research, 44(D1): D1080–D1086. Doi: 10.1093/nar/gkv1192

Liu, J., Mansouri, K., Judson, R.S., Martin, M.T., Hong, H., Chen, M., Xu, X., Thomas, R.S. & Shah, I. (2015). Predicting Hepatotoxicity Using Toxcast In Vitro Bioactivity and Chemical Structure. Chemical Research in Toxicology, 28(4): 738–751. DOI: 10.1021/tx500501h

Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, Li HB. Bioactive Compounds and Bioactivities of Ginger (Zingiber officinale Roscoe). Foods. 2019 May 30;8(6):185. doi: 10.3390/foods8060185.

Lubarska M, Hałasiński P, Hryhorowicz S, Mahadea DS, Łykowska-Szuber L, Eder P, Dobrowolska A, Krela-Kaźmierczak I. (2023). Liver Dangers of Herbal Products: A Case Report of Ashwagandha-Induced Liver Injury. Int J Environ Res Public Health. 20(5):3921. doi: 10.3390/ijerph20053921

Wei CK, Tsai YH, Korinek M, Hung PH, El-Shazly M, Cheng YB, Wu YC, Hsieh TJ, Chang FR. (2017). 6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice. Int J Mol Sci. Jan 17;18(1):168.

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Published

2024-03-29

How to Cite

Frimayanti, N., Febrina, M. ., & Yuri Amalia, A. (2024). A New Insight Into Toxicity of Database Compounds from Ginger (Zingiber officinale) by Modelling Study. Jurnal Riset Kimia, 15(1), 17–28. https://doi.org/10.25077/jrk.v15i1.638

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Vol. 15 No. 1 (2024): March

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