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Determination of Potential Anti-Alzheimer Activity of Gentiopicroside and Isoorientin Using Molecular Docking Studies

Year 2021, Volume: 12 , 106 - 112, 31.12.2021

Nida Nur Derelı-calıskan Mehmet Tahir Husunet Hasan Basri Ila Işık Didem Karagoz

https://doi.org/10.55549/epstem.1038383

Abstract

Alzheimer's disease (AD) is the most common type of dementia worldwide, involving a multifactorial combination of environmental, genetic and epigenetic factors. It is characterized by the accumulation of abnormal amyloid beta (Aß) and tau fibrillar tangles, oxidative stress, neuroinflammation, and disruption of autophagy mechanisms. The agents used for the treatment of the disease only prevent the symptoms of the disease. Epigenetic modifications such as DNA methylations and histone modifications that occur in learning and memory processes have come to the fore in the search for new and reliable potential therapeutic agents for AD. Against these multiple mechanisms of AD, natural products are currently considered an alternative strategy for the discovery of new multipotent drugs. Phytocompounds of Gentiana olivieri, Gentiopicroside and Isoorientin, which have been known to have many benefits for health, act as a neuroprotective effect by acting as an anti-inflammatory and antioxidant. Based on this, in order to determine the possible effects of Gentiopicroside and Isoorientin phytocompounds on Sirtüin-1 (SIRT1), Sirtüin-2 (SIRT2), Sestrin 2 (SESN2), Histone deacetyl transferase-6 (HDAC6) and divalent metal transporter 1 (DMT1) enzymes, which are seen as targets in AD, molecular docking analysis was carried out. AutoDock 4.0 software was used to predict the interaction of ligands with possible active binding sites on the target molecule crystal structure. As a result of the analyzes, the best coupling occurred between the Gentiopicroside and DMT1 and HDAC6 enzymes. In the light of this information, it can be suggested that the molecular clamping analysis is carried out by the neuroprotective effect of Gentiopicroside by DMT1 enzyme inhibition, while Izoorientine performs through the HDAC6 enzyme. As a result, it is thought that our results will contribute to the search for new therapeutic agent studies using epigenetic approaches against AD.

Keywords

Alzheimer molecular docking epigenetic modifications Isoorientin Gentiopicroside

References

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  • Bertos, N. R., Gilquin, B., Chan, G. K., Yen, T. J., Khochbin, S., & Yang, X. J. (2004). Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. The Journal of biological chemistry, 279(46), 48246–48254. https://doi.org/10.1074/jbc.M408583200
  • Cacabelos, R., Carril, J. C., Cacabelos, N., Kazantsev, A. G., Vostrov, A. V., Corzo, L., Cacabelos, P., & Goldgaber, D. (2019). Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics. International journal of molecular sciences, 20(5), 1249. https://doi.org/10.3390/ijms20051249
  • Chen, L., Liu, J.C., Zhang, XN., Guo, YY., Xu, ZH., Cao, W., et al. (2008). “Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain”, Neuropharmacology, 54,1175–1181
  • Chen, Y. S., Der Chen, S., Wu, C. L.,. Huang, S. S., & Yang, D. I. (2014). Induction of sestrin2 as an endogenous protective mechanism against amyloid beta-peptide neurotoxicity in primary cortical culture. Exp. Neurol., vol. 253, pp. 63–71.
  • Deng, Y.T., Wang, X.S., Zhao, M.G., Huang, X.X., & Xu, X.L. (2018). “Gentiopicroside protects neurons from astrocyte-mediated inflammatory injuries by inhibition of nuclear factor-κB and mitogen-activated protein kinase signaling pathways”. NeuroReport, 29, 1114–1120.
  • Ding, H., Dolan, P. J., & Johnson, G. V. (2008). Histone deacetylase 6 interacts with the microtubule-associated protein tau. Journal of neurochemistry, 106(5), 2119–2130. https://doi.org/10.1111/j.1471-4159.2008.05564.x
  • Duce, J. A., & Bush, A. I. (2010). Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics. Progress in Neurobiology, 92(1), 1–18. https://doi.org/10.1016/j.pneurobio.2010.04.003
  • Falkenberg, K. J., & Johnstone, R. W. (2014). Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nature reviews. Drug Discovery, 13(9), 673–691. https://doi.org/10.1038/nrd4360
  • Gregoretti, I. V., Lee, Y. M., & Goodson, H. V. (2004). Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. Journal of Molecular Biology, 338(1), 17–31. https://doi.org/10.1016/j.jmb.2004.02.006
  • Heinisch, J. J., & Brandt, R. (2016). Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells. Microbial cell (Graz, Austria), 3(4), 135–146. https://doi.org/10.15698/mic2016.04.489
  • Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X. F., & Yao, T. P. (2002). HDAC6 is a microtubule-associated deacetylase. Nature, 417(6887), 455–458. https://doi.org/10.1038/417455a
  • Ingrassia, R., Garavaglia, B., & Memo, M. (2019). DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration. Frontiers in Neuroscience, 13, 575. https://doi.org/10.3389/fnins.2019.00575
  • Konsoula, Z., & Barile, F. A. (2012). Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders. Journal of Pharmacological and Toxicological Methods, 66(3), 215–220. https://doi.org/10.1016/j.vascn.2012.08.001
  • Kovacs, J. J., Murphy, P. J., Gaillard, S., Zhao, X., Wu, J. T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B., & Yao, T. P. (2005). HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Molecular Cell, 18(5), 601–607. https://doi.org/10.1016/j.molcel.2005.04.021
  • Liang, Z., Zhang, B., Su, W.W., Wiliams, P.G., Li, Q.X. (2016). “C-Glycosylflavones Alleviate Tau Phosphorylation and Amyloid Neurotoxicity through GSK3# Inhibition” , ACS Chemical Neuroscience
  • Liu., S.B., Zhao, R., Li, X.S., Guo, H.J., Tian, Z., Zhang, N., et al. (2014). “Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice”. Neuromolecular Medicine, 16,350–359.
  • Lu, X., Wang, L., Yu, C., Yu, D., & Yu, G. (2015). Histone acetylation modifiers in the pathogenesis of Alzheimer's disease. Frontiers in Cellular Neuroscience, 9, 226. https://doi.org/10.3389/fncel.2015.00226
  • Ma, N., Luo, Y., Wang, Y., Liao, C., Ye, W. C., & Jiang, S. (2016). Selective histone deacetylase ınhibitors with anticancer activity. Current Topics in Medicinal Chemistry, 16(4), 415–426. https://doi.org/10.2174/1568026615666150813145629
  • Mastroeni, D., Grover, A., Delvaux, E., Whiteside, C., Coleman, P. D., & Rogers, J. (2011). Epigenetic mechanisms in Alzheimer's disease. Neurobiology of Aging, 32(7), 1161–1180. https://doi.org/10.1016/j.neurobiolaging.2010.08.017
  • Nagoor Meeran, M. F., Javed, H., Al Taee, H., Azimullah, S., & Ojha, S. K. (2017). Pharmacological properties and molecular mechanisms of thymol: Prospects for Its therapeutic potential and pharmaceutical development. Frontiers in Pharmacology, 8, 380. https://doi.org/10.3389/fphar.2017.00380
  • Suganuma, T., & Workman, J. L. (2008). Crosstalk among histone modifications. Cell, 135(4), 604–607. https://doi.org/10.1016/j.cell.2008.10.036
  • Szyk, A., Deaconescu, A. M., Spector, J., Goodman, B., Valenstein, M. L., Ziolkowska, N. E., Kormendi, V., Grigorieff, N., & Roll-Mecak, A. (2014). Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell, 157(6), 1405–1415. https://doi.org/10.1016/j.cell.2014.03.061
  • Tiiman, A., Palumaa, P., & Tõugu, V. (2013). The missing link in the amyloid cascade of Alzheimer's disease - metal ions. Neurochemistry International, 62(4), 367–378. https://doi.org/10.1016/j.neuint.2013.01.023
  • Verdin, E., & Ott, M. (2015). 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nature reviews. Molecular Cell Biology, 16(4), 258–264. https://doi.org/10.1038/nrm3931
  • Wang, J., Yu, J. T., Tan, M. S., Jiang, T., & Tan, L. (2013). Epigenetic mechanisms in Alzheimer's disease: implications for pathogenesis and therapy. Ageing Research Reviews, 12(4), 1024–1041. https://doi.org/10.1016/j.arr.2013.05.003
  • Zheng, W., Xin, N., Chi, Z. H., Zhao, B. L., Zhang, J., Li, J. Y., & Wang, Z. Y. (2009). Divalent metal transporter 1 is involved in amyloid precursor protein processing and Abeta generation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 23(12), 4207–4217. https://doi.org/10.1096/fj.09-135749

Year 2021, Volume: 12 , 106 - 112, 31.12.2021

Nida Nur Derelı-calıskan Mehmet Tahir Husunet Hasan Basri Ila Işık Didem Karagoz

https://doi.org/10.55549/epstem.1038383

Abstract

References

  • 2020 Alzheimer's disease facts and figures. (2020). Alzheimer's & dementia : the journal of the Alzheimer's Association, 10.1002/alz.12068. Advance online publication. https://doi.org/10.1002/alz.12068
  • Bertos, N. R., Gilquin, B., Chan, G. K., Yen, T. J., Khochbin, S., & Yang, X. J. (2004). Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. The Journal of biological chemistry, 279(46), 48246–48254. https://doi.org/10.1074/jbc.M408583200
  • Cacabelos, R., Carril, J. C., Cacabelos, N., Kazantsev, A. G., Vostrov, A. V., Corzo, L., Cacabelos, P., & Goldgaber, D. (2019). Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics. International journal of molecular sciences, 20(5), 1249. https://doi.org/10.3390/ijms20051249
  • Chen, L., Liu, J.C., Zhang, XN., Guo, YY., Xu, ZH., Cao, W., et al. (2008). “Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain”, Neuropharmacology, 54,1175–1181
  • Chen, Y. S., Der Chen, S., Wu, C. L.,. Huang, S. S., & Yang, D. I. (2014). Induction of sestrin2 as an endogenous protective mechanism against amyloid beta-peptide neurotoxicity in primary cortical culture. Exp. Neurol., vol. 253, pp. 63–71.
  • Deng, Y.T., Wang, X.S., Zhao, M.G., Huang, X.X., & Xu, X.L. (2018). “Gentiopicroside protects neurons from astrocyte-mediated inflammatory injuries by inhibition of nuclear factor-κB and mitogen-activated protein kinase signaling pathways”. NeuroReport, 29, 1114–1120.
  • Ding, H., Dolan, P. J., & Johnson, G. V. (2008). Histone deacetylase 6 interacts with the microtubule-associated protein tau. Journal of neurochemistry, 106(5), 2119–2130. https://doi.org/10.1111/j.1471-4159.2008.05564.x
  • Duce, J. A., & Bush, A. I. (2010). Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics. Progress in Neurobiology, 92(1), 1–18. https://doi.org/10.1016/j.pneurobio.2010.04.003
  • Falkenberg, K. J., & Johnstone, R. W. (2014). Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nature reviews. Drug Discovery, 13(9), 673–691. https://doi.org/10.1038/nrd4360
  • Gregoretti, I. V., Lee, Y. M., & Goodson, H. V. (2004). Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. Journal of Molecular Biology, 338(1), 17–31. https://doi.org/10.1016/j.jmb.2004.02.006
  • Heinisch, J. J., & Brandt, R. (2016). Signaling pathways and posttranslational modifications of tau in Alzheimer's disease: the humanization of yeast cells. Microbial cell (Graz, Austria), 3(4), 135–146. https://doi.org/10.15698/mic2016.04.489
  • Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X. F., & Yao, T. P. (2002). HDAC6 is a microtubule-associated deacetylase. Nature, 417(6887), 455–458. https://doi.org/10.1038/417455a
  • Ingrassia, R., Garavaglia, B., & Memo, M. (2019). DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration. Frontiers in Neuroscience, 13, 575. https://doi.org/10.3389/fnins.2019.00575
  • Konsoula, Z., & Barile, F. A. (2012). Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders. Journal of Pharmacological and Toxicological Methods, 66(3), 215–220. https://doi.org/10.1016/j.vascn.2012.08.001
  • Kovacs, J. J., Murphy, P. J., Gaillard, S., Zhao, X., Wu, J. T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B., & Yao, T. P. (2005). HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Molecular Cell, 18(5), 601–607. https://doi.org/10.1016/j.molcel.2005.04.021
  • Liang, Z., Zhang, B., Su, W.W., Wiliams, P.G., Li, Q.X. (2016). “C-Glycosylflavones Alleviate Tau Phosphorylation and Amyloid Neurotoxicity through GSK3# Inhibition” , ACS Chemical Neuroscience
  • Liu., S.B., Zhao, R., Li, X.S., Guo, H.J., Tian, Z., Zhang, N., et al. (2014). “Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice”. Neuromolecular Medicine, 16,350–359.
  • Lu, X., Wang, L., Yu, C., Yu, D., & Yu, G. (2015). Histone acetylation modifiers in the pathogenesis of Alzheimer's disease. Frontiers in Cellular Neuroscience, 9, 226. https://doi.org/10.3389/fncel.2015.00226
  • Ma, N., Luo, Y., Wang, Y., Liao, C., Ye, W. C., & Jiang, S. (2016). Selective histone deacetylase ınhibitors with anticancer activity. Current Topics in Medicinal Chemistry, 16(4), 415–426. https://doi.org/10.2174/1568026615666150813145629
  • Mastroeni, D., Grover, A., Delvaux, E., Whiteside, C., Coleman, P. D., & Rogers, J. (2011). Epigenetic mechanisms in Alzheimer's disease. Neurobiology of Aging, 32(7), 1161–1180. https://doi.org/10.1016/j.neurobiolaging.2010.08.017
  • Nagoor Meeran, M. F., Javed, H., Al Taee, H., Azimullah, S., & Ojha, S. K. (2017). Pharmacological properties and molecular mechanisms of thymol: Prospects for Its therapeutic potential and pharmaceutical development. Frontiers in Pharmacology, 8, 380. https://doi.org/10.3389/fphar.2017.00380
  • Suganuma, T., & Workman, J. L. (2008). Crosstalk among histone modifications. Cell, 135(4), 604–607. https://doi.org/10.1016/j.cell.2008.10.036
  • Szyk, A., Deaconescu, A. M., Spector, J., Goodman, B., Valenstein, M. L., Ziolkowska, N. E., Kormendi, V., Grigorieff, N., & Roll-Mecak, A. (2014). Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell, 157(6), 1405–1415. https://doi.org/10.1016/j.cell.2014.03.061
  • Tiiman, A., Palumaa, P., & Tõugu, V. (2013). The missing link in the amyloid cascade of Alzheimer's disease - metal ions. Neurochemistry International, 62(4), 367–378. https://doi.org/10.1016/j.neuint.2013.01.023
  • Verdin, E., & Ott, M. (2015). 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nature reviews. Molecular Cell Biology, 16(4), 258–264. https://doi.org/10.1038/nrm3931
  • Wang, J., Yu, J. T., Tan, M. S., Jiang, T., & Tan, L. (2013). Epigenetic mechanisms in Alzheimer's disease: implications for pathogenesis and therapy. Ageing Research Reviews, 12(4), 1024–1041. https://doi.org/10.1016/j.arr.2013.05.003
  • Zheng, W., Xin, N., Chi, Z. H., Zhao, B. L., Zhang, J., Li, J. Y., & Wang, Z. Y. (2009). Divalent metal transporter 1 is involved in amyloid precursor protein processing and Abeta generation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 23(12), 4207–4217. https://doi.org/10.1096/fj.09-135749
There are 27 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Articles
Authors

Nida Nur Derelı-calıskan

Mehmet Tahir Husunet

Hasan Basri Ila

Işık Didem Karagoz

Early Pub Date September 5, 2021
Publication Date December 31, 2021
Published in Issue Year 2021 Volume: 12

Cite

APA Derelı-calıskan, N. N., Husunet, M. T., Ila, H. B., Karagoz, I. D. (2021). Determination of Potential Anti-Alzheimer Activity of Gentiopicroside and Isoorientin Using Molecular Docking Studies. The Eurasia Proceedings of Science Technology Engineering and Mathematics, 12, 106-112. https://doi.org/10.55549/epstem.1038383
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