In silico investigation of bioactive compounds from Ginkgo biloba as alternatives to non-steroidal anti-inflammatory drugs
Non-steroidal Anti-inflammatory Drugs (NSAIDs) are common over-the-counter drugs that are used for numerous inflammation-associated ailments. Despite their widespread consumption, these synthetic drugs are not without side effects. Adversities caused by NSAIDs range from simple nausea and vomiting to fatal conditions such as hypertension, gastrointestinal bleeding and diminished renal function. There is thus a need to develop novel alternatives to these drugs which possess comparable efficacies. Phytocompounds are attractive alternatives for a plethora of medicines used for various disorders and diseases as they are readily available in nature and have negligible side effects. In an attempt to identify safe alternatives to NSAIDs, we tested six bioactive compounds from Ginkgo biloba (Ginkgolide A, Amentoflavone, Bilobetin, Ginkgetin, Quercetin, and Bilobalide) for their abilities to inhibit Cyclooxygenase-1, Cyclooxygenase-2 and 5-Lipoxygenase which are inflammation-causing enzymes. Molecular docking experiments using Autodock Vina resulted in binding energy values between -6.6 and -11.9 kcal/mol, comparable to that of control drugs, which indicated that the tested phytocompounds were able to bind strongly to the active sites of the three proteins. Analyses of receptor-ligand interactions using Discovery Studio Visualizer revealed that all the tested compounds formed numerous non-covalent interactions with the surrounding amino acid residues, which confirmed their binding stabilities. Finally, evaluation of their drug likeness based on Lipinski’s rule of five showed that the tested G. biloba compounds possess the potential to be taken as oral drugs to replace conventional NSAIDs.
Attie, A. D., & Raines, R. T. (2017). Analysis of Receptor – Ligand Interactions. 72(2), 119–124. https://doi.org/10.1021/ed072p119.Analysis
Benet, L. Z., Hosey, C. M., Ursu, O., & Oprea, T. I. (2016). BDDCS, the Rule of 5 and drugability. In Advanced Drug Delivery Reviews (Vol. 101). https://doi.org/10.1016/j.addr.2016.05.007
Chan, P. C., Xia, Q., & Fu, P. P. (2007). Ginkgo biloba leave extract: Biological, medicinal, and toxicological effects. Journal of Environmental Science and Health - Part C Environmental Carcinogenesis and Ecotoxicology Reviews, 25(3), 211–244. https://doi.org/10.1080/10590500701569414
Cheke, R. S. (2020). The Molecular Docking Study of Potential Drug Candidates Showing Anti-COVID-19 Activity by Exploring of Therapeutic Targets of SARS-CoV-2. Eurasian Journal of Medicine and Oncology, 4(3), 185–195. https://doi.org/10.14744/ejmo.2020.31503
D Studio, & . (2008). Discovery Studio Life Science Modeling and Simulations. Researchgate.Net, 1–8.
Davis, A., & Robson, J. (2016). The dangers of NSAIDs: Look both ways. British Journal of General Practice, 66(645), 172–173. https://doi.org/10.3399/bjgp16X684433
Du, X., Li, Y., Xia, Y. L., Ai, S. M., Liang, J., Sang, P., Ji, X. L., & Liu, S. Q. (2016). Insights into protein–ligand interactions: Mechanisms, models, and methods. International Journal of Molecular Sciences, 17(2), 1–34. https://doi.org/10.3390/ijms17020144
Ferreira De Freitas, R., & Schapira, M. (2017). A systematic analysis of atomic protein-ligand interactions in the PDB. MedChemComm, 8(10), 1970–1981. https://doi.org/10.1039/c7md00381a
Forni, C., Facchiano, F., Bartoli, M., Pieretti, S., Facchiano, A., D’Arcangelo, D., Norelli, S., Valle, G., Nisini, R., Beninati, S., Tabolacci, C., & Jadeja, R. N. (2019). Beneficial role of phytochemicals on oxidative stress and age-related diseases. BioMed Research International, 2019(Figure 1). https://doi.org/10.1155/2019/8748253
Giménez, B. G., Santos, M. S., Ferrarini, M., & Dos Santos Fernandes, J. P. (2010). Evaluation of blockbuster drugs under the rule-of-five. Pharmazie, 65(2), 148–152. https://doi.org/10.1691/ph.2010.9733
Gunaydin, C., & Bilge, S. S. (2018). Effects of nonsteroidal anti-inflammatory drugs at the molecular level. Eurasian Journal of Medicine, 50(2), 116–121. https://doi.org/10.5152/eurasianjmed.2018.0010
Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeerschd, T., Zurek, E., & Hutchison, G. R. (2012). Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics, 4(8). https://doi.org/10.1186/1758-2946-4-17
Hariono, M., Abdullah, N., Damodaran, K. V., Kamarulzaman, E. E., Mohamed, N., Hassan, S. S., Shamsuddin, S., & Wahab, H. A. (2016). Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay. Scientific Reports, 6(November), 1–10. https://doi.org/10.1038/srep38692
Hossen, I., Hua, W., Ting, L., Mehmood, A., Jingyi, S., Duoxia, X., Yanping, C., Hongqing, W., Zhipeng, G., Kaiqi, Z., Fang, Y., & Junsong, X. (2020). Phytochemicals and inflammatory bowel disease: a review. Critical Reviews in Food Science and Nutrition, 60(8), 1321–1345. https://doi.org/10.1080/10408398.2019.1570913
Hu, C., & Ma, S. (2018). Recent development of lipoxygenase inhibitors as anti-inflammatory agents. MedChemComm, 9(2), 212–225. https://doi.org/10.1039/c7md00390k
Ilhan, N., Susam, S., Ak, T. P., & Baykalir, B. G. (2018). The antiiflammatory effect of Ginkgo biloba in lipopolysaccharide-induced rat sepsis model. Journal of Laboratory Medicine, 42(1–2), 45–49. https://doi.org/10.1515/labmed-2017-0113
Lipinski, C. A. (2004). Lead- and drug-like compounds: The rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007
Mihiri Shashikala, H. B., Chakravorty, A., & Alexov, E. (2019). Modeling electrostatic force in protein-protein recognition. Frontiers in Molecular Biosciences, 6(SEP), 1–11. https://doi.org/10.3389/fmolb.2019.00094
Mukhi, M., & Jai, J. (2020). Evaluating the potency of three plant compounds as HDAC Inhibitors for the treatment of Huntington’s disease: An in silico study. International Journal of Herbal Medicine, 8(5), 10–13.
NSAIDs. nhs.uk. (2019). Retrieved 22 February 2022, from https://www.nhs.uk/conditions/nsaids/#:~:text=Non%2Dsteroidal%20anti%2Dinflammatory%20drugs,causes%20of%20long%2Dterm%20pain.
Pacheco, A. B., & Hpc, L. S. U. (2012). Introduction to AutoDock and AutoDock Tools.
Pantsar, T., & Poso, A. (2018). Binding affinity via docking: Fact and fiction. Molecules, 23(8), 1DUMMY. https://doi.org/10.3390/molecules23081899
Shah, Z. A., Nada, S. E., & Doré, S. (2011). Heme oxygenase 1, beneficial role in permanent ischemic stroke and in Gingko biloba (EGb 761) neuroprotection. Neuroscience, 180, 248–255. https://doi.org/10.1016/j.neuroscience.2011.02.031
Son, J. K., Son, M. J., Lee, E., Moon, T. C., Son, K. H., Kim, C. H., Kim, H. P., Kang, S. S., & Chang, H. W. (2005). Ginkgetin, a biflavone from Ginko biloba leaves, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells. Biological and Pharmaceutical Bulletin, 28(12), 2181–2184. https://doi.org/10.1248/bpb.28.2181
Tallei, T. E., Tumilaar, S. G., Niode, N. J., Fatimawali, Kepel, B. J., Idroes, R., Effendi, Y., Sakib, S. A., & Emran, T. Bin. (2020). Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study. Scientifica, 2020. https://doi.org/10.1155/2020/6307457
Tao, Z., Jin, W., Ao, M., Zhai, S., Xu, H., & Yu, L. (2019). Evaluation of the anti-inflammatory properties of the active constituents in Ginkgo biloba for the treatment of pulmonary diseases. Food and Function, 10(4), 2209–2220. https://doi.org/10.1039/c8fo02506a
Tian, X. Q., Zhang, L. Da, Wang, J. M., Dai, J. G., Shen, S. S., Yang, L., & Huang, P. L. (2013). The protective effect of hyperbaric oxygen and Ginkgo biloba extract on Aβ25-35-induced oxidative stress and neuronal apoptosis in rats. Behavioural Brain Research, 242(1), 1–8. https://doi.org/10.1016/j.bbr.2012.12.026
Tulsulkar, J., & Shah, Z. A. (2013). Ginkgo biloba prevents transient global ischemia-induced delayed hippocampal neuronal death through antioxidant and anti-inflammatory mechanism. Neurochemistry International, 62(2), 189–197. https://doi.org/10.1016/j.neuint.2012.11.017
Wishart, D. S., Knox, C., Guo, A. C., Cheng, D., Shrivastava, S., Tzur, D., Gautam, B., & Hassanali, M. (2008). DrugBank: A knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Research, 36(SUPPL. 1), 901–906. https://doi.org/10.1093/nar/gkm958
Wolfe, D., Yazdi, F., Kanji, S., Burry, L., Beck, A., Butler, C., Esmaeilisaraji, L., Hamel, C., Hersi, M., Skidmore, B., Moher, D., & Hutton, B. (2018). Incidence, causes, and consequences of preventable adverse drug reactions occurring in inpatients: A systematic review of systematic reviews. In PLoS ONE (Vol. 13, Issue 10). https://doi.org/10.1371/journal.pone.0205426
Zhang, Y. J., Gan, R. Y., Li, S., Zhou, Y., Li, A. N., Xu, D. P., Li, H. Bin, & Kitts, D. D. (2015). Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules, 20(12), 21138–21156. https://doi.org/10.3390/molecules201219753
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