Confirmation of the Experimentally-Proven Therapeutic Utility of Madecassoside in an Aβ1-42 Infusion Rat Model of Alzheimer’s Disease by in Silico Analyses
Author(s)
Abdullah Al Mamun1,
Michio Hashimoto1*,
Shahdat Hossain1,2,
Masanori Katakura1,
Hiroyuki Arai3,
Osamu Shido1
Affiliation(s)
1 Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumoshi, Japan. 2 Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Dhaka, Bangladesh. 3 Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
1 Department of Environmental Physiology, Shimane University Faculty of Medicine, Izumoshi, Japan. 2 Laboratory of Alternative Medicine and Behavioral Neurosciences, Department of Biochemistry and Molecular Biology, Jahangirnagar University, Dhaka, Bangladesh. 3 Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
ABSTRACT
The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madecassoside, an active component of Centella asiatica, improved memory impairment in an Aβ1-42 infusion rat model of AD, ameliorated neurotoxicity in SH-SY5Y cells, and inhibited in vitro Aβ1-42 fibril formation. In the present study, we investigated the utility of in silico analyses in corroborating observed in vivo and in vitro effects of madecassoside in AD to further assess the therapeutic benefits of madecassoside. The 3D structure of Aβ1-42 was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The binding of madecassoside to Aβ1-42 was assessed by molecular docking. The chemical structure of madecassoside was modeled and converted to the PDB format. Madecassoside was found to successfully dock with Aβ1-42. Computational demonstration of the binding of madecassoside to Aβ1-42 further corroborated the inhibitory effect of madecassoside on Aβ1-42 fibrillogenesis which was demonstrated in our previous study. These data showed the potential utility of madecassoside as a preventive medication in Aβ1-42-induced neurodegenerative diseases such as AD.
The accumulation of amyloid β peptide 1 - 42 (Aβ1-42) in the brain of Alzheimer’s disease (AD) patients is known to be associated with neurodegeneration and memory impairment. More recently, we reported that madecassoside, an active component of Centella asiatica, improved memory impairment in an Aβ1-42 infusion rat model of AD, ameliorated neurotoxicity in SH-SY5Y cells, and inhibited in vitro Aβ1-42 fibril formation. In the present study, we investigated the utility of in silico analyses in corroborating observed in vivo and in vitro effects of madecassoside in AD to further assess the therapeutic benefits of madecassoside. The 3D structure of Aβ1-42 was downloaded from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB). The binding of madecassoside to Aβ1-42 was assessed by molecular docking. The chemical structure of madecassoside was modeled and converted to the PDB format. Madecassoside was found to successfully dock with Aβ1-42. Computational demonstration of the binding of madecassoside to Aβ1-42 further corroborated the inhibitory effect of madecassoside on Aβ1-42 fibrillogenesis which was demonstrated in our previous study. These data showed the potential utility of madecassoside as a preventive medication in Aβ1-42-induced neurodegenerative diseases such as AD.
Cite this paper
Mamun, A. , Hashimoto, M. , Hossain, S. , Katakura, M. , Arai, H. and Shido, O. (2015) Confirmation of the Experimentally-Proven Therapeutic Utility of Madecassoside in an Aβ1-42 Infusion Rat Model of Alzheimer’s Disease by in Silico Analyses. Advances in Alzheimer's Disease, 4, 37-44. doi: 10.4236/aad.2015.42005.
Mamun, A. , Hashimoto, M. , Hossain, S. , Katakura, M. , Arai, H. and Shido, O. (2015) Confirmation of the Experimentally-Proven Therapeutic Utility of Madecassoside in an Aβ1-42 Infusion Rat Model of Alzheimer’s Disease by in Silico Analyses. Advances in Alzheimer's Disease, 4, 37-44. doi: 10.4236/aad.2015.42005.
References
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http://dx.doi.org/10.1016/0896-6273(91)90052-2 [2] Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N. and Ihara, Y. (1994) Visualization of Aβ 42(43) and Aβ40 in Senile Plaques with End-Specific Aβ Monoclonals: Evidence That an Initially Deposited Species Is Aβ 42(43). Neuron, 13, 45-53. http://dx.doi.org/10.1016/0896-6273(94)90458-8 [3] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y.Q., Jorm, A., Mathers, C., Menezes, P.R., Rimmer, E. and Scazufca, M. (2005) Global Prevalence of Dementia: A Delphi Consensus Study. The Lancet, 366, 2112-2117.
http://dx.doi.org/10.1016/S0140-6736(05)67889-0 [4] Wanasuntronwong, A., Tantisira, M.H., Tantisira, B. and Watanabe, H. (2012) Anxiolytic Effects of Standardized Extract of Centella asiatica (ECa 233) after Chronic Immobilization Stress in Mice. Journal of Ethnopharmacology, 143, 579-585. http://dx.doi.org/10.1016/j.jep.2012.07.010 [5] Hossain, S., Hashimoto, M., Katakura, M. and Shido, O. (2013) Asiaticoside and Madecassoside, Two Major Glycosides of Centella asiatica Inhibit the in Vitro Amyloid Beta Peptide Aβ1-42 Fibrillation—Assessed by FCS, Capable of Detecting Single Molecular Movement and Interaction. Proceedings of the 11th International Conference on Alzheimer’s & Parkinson’s Diseases, Florence, 6-10 March 2013, 245. [6] Mamun, A.A., Hashimoto, M., Katakura, M., Matsuzaki, K., Hossain, S., Arai, H. and Shido, O. (2014) Neuroprotective Effect of Madecassoside Evaluated Using Amyloid β1-42-Mediated in Vitro and in Vivo Alzheimer’s Disease Models. International Journal of Indigenous Medicinal Plants, 47, 1669-1682. [7] Marvin (2011) Marvin Was Used for Drawing, Displaying and Characterizing Chemical Structures, Substructures and Reactions, Marvin 5.7. [8] Thomsen, R. and Christensen, M.H. (2006) MolDock: A New Technique for High-Accuracy Molecular Docking. Journal of Medicinal Chemistry, 49, 3315-3321. http://dx.doi.org/10.1021/jm051197e [9] Lührs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Döbeli, H., Schubert, D. and Riek, R. (2005) 3D Structure of Alzheimer’s Amyloid-Beta (1-42) Fibrils. roceedings of the National Academy of Sciences of the United States of America, 102, 17342-17347. http://dx.doi.org/10.1073/pnas.0506723102 [10] Lyskov, S. and Gray, J.J. (2008) The RosettaDock Server for Local Protein-Protein Docking. Nucleic Acids Research, 36, W233-W238. http://dx.doi.org/10.1093/nar/gkn216 [11] Duhovny, D., Nussinov, R. and Wolfson, H.J. (2002) Efficient Unbound Docking of Rigid Molecules. In: Guigó, R. and Gusfield, D., Eds., Proceedings of the 2nd Workshop on Algorithms in Bioinformatics (WABI) Rome, Italy, Lecture Notes in Computer Science (LNCS) 2452, Springer Verlag, Berlin Heidelberg, 185-200. [12] Hossain, S., Hashimoto, M., Katakura, M., Miwa, K., Shimada, T. and Shido, O. (2009) Mechanism of Docosahexaenoic Acid-Induced Inhibition of in Vitro Aβ1-42 Fibrillation and Aβ1-42-Induced Toxicity in SH-S5Y5 Cells. Journal of Neurochemistry, 111, 568-579.
http://dx.doi.org/10.1111/j.1471-4159.2009.06336.x [13] Hashimoto, M., Hossain, S., Yamashita, S., Katakura, M., Tanabe, Y., Fujiwara, H., Gamoh, S., Miyazawa, T., Arai, H., Shimada, T. and Shido, O. (2008) Docosahexaenoic Acid Disrupts in Vitro Amyloid β1-40 Fibrillation and Concomitantly Inhibits Amyloid Levels in Cerebral Cortex of Alzheimer’s Disease Model Rats. Journal of Neurochemistry, 107, 1634-1646. http://dx.doi.org/10.1111/j.1471-4159.2008.05731.x [14] Hashimoto, M., Hossain, S., Katakura, M., Mamun, A.A. and Shido, O. (2015) The Binding of Aβ1-42 to Lipid Rafts of RBC Is Enhanced by Dietary Docosahexaenoic Acid in Rats: Implicates to Alzheimer’s Disease. Biochimica et Biophysica Acta, 1848, 1402-1409. http://dx.doi.org/10.1016/j.bbamem.2015.03.008 [15] Hashimoto, M., Hossain, S., Hossain, S., Rahman, A., Shimada, T. and Shido, O. (2011) Docosahexaenoic Acid Withstands the Aβ25-35-Induced Neurotoxicity in SH-SY5Y Cells. The Journal of Nutritional Biochemistry, 22, 22-29. http://dx.doi.org/10.1016/j.jnutbio.2009.11.005 [16] Groenning, M. (2009) Binding Mode of Thioflavin T and Other Molecular Probes in the Context of Amyloid Fibrils- Current Status. Journal of Chemical Biology, 3, 1-18.
http://dx.doi.org/10.1007/s12154-009-0027-5 [17] Kim, Y., Lee, J.H., Ryu, J. and Kim, D.J. (2009) Multivalent & Multifunctional Ligands to Beta-Amyloid. Current Pharmaceutical Design, 15, 637-658. http://dx.doi.org/10.2174/138161209787315648 [18] Nilsson, K.P. (2009) Small Organic Probes as Amyloid Specific Ligands-Past and Recent Molecular Scaffolds. FEBS Letters, 583, 2593-2599. http://dx.doi.org/10.1016/j.febslet.2009.04.016 [19] Hossain, S., Hashimoto, M., Katakura, M., Mamun, A.A. and Shido, O. (2015) Medicinal Value of Asiaticoside for Alzheimer’s Disease as Assessed Using Single-Molecule-Detection Fluorescence Correlation Spectroscopy, Laser- Scanning Microscopy, Transmission Electron Microscopy, and in Silico Docking. BMC Complementary and Alternative Medicine, 15, in Press. http://dx.doi.org/10.1186/s12906-015-0620-9 [20] Sirk, T.W., Friedman, M. and Brown, E.F. (2011) Molecular Binding of Black Tea Theaflavins to Biological Membranes: Relationship to Bioactivities. Journal of Agricultural and Food Chemistry, 59, 3780-3787.
http://dx.doi.org/10.1021/jf2006547 [21] Stefani, M.S. (2013) Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds. International Journal of Molecular Sciences, 14, 12411-12457.
http://dx.doi.org/10.3390/ijms140612411
[1] Selkoe, D.J. (1991) The Molecular Pathology of Alzheimer’s Disease. Neuron, 6, 487-498.
http://dx.doi.org/10.1016/0896-6273(91)90052-2 [2] Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N. and Ihara, Y. (1994) Visualization of Aβ 42(43) and Aβ40 in Senile Plaques with End-Specific Aβ Monoclonals: Evidence That an Initially Deposited Species Is Aβ 42(43). Neuron, 13, 45-53. http://dx.doi.org/10.1016/0896-6273(94)90458-8 [3] Ferri, C.P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y.Q., Jorm, A., Mathers, C., Menezes, P.R., Rimmer, E. and Scazufca, M. (2005) Global Prevalence of Dementia: A Delphi Consensus Study. The Lancet, 366, 2112-2117.
http://dx.doi.org/10.1016/S0140-6736(05)67889-0 [4] Wanasuntronwong, A., Tantisira, M.H., Tantisira, B. and Watanabe, H. (2012) Anxiolytic Effects of Standardized Extract of Centella asiatica (ECa 233) after Chronic Immobilization Stress in Mice. Journal of Ethnopharmacology, 143, 579-585. http://dx.doi.org/10.1016/j.jep.2012.07.010 [5] Hossain, S., Hashimoto, M., Katakura, M. and Shido, O. (2013) Asiaticoside and Madecassoside, Two Major Glycosides of Centella asiatica Inhibit the in Vitro Amyloid Beta Peptide Aβ1-42 Fibrillation—Assessed by FCS, Capable of Detecting Single Molecular Movement and Interaction. Proceedings of the 11th International Conference on Alzheimer’s & Parkinson’s Diseases, Florence, 6-10 March 2013, 245. [6] Mamun, A.A., Hashimoto, M., Katakura, M., Matsuzaki, K., Hossain, S., Arai, H. and Shido, O. (2014) Neuroprotective Effect of Madecassoside Evaluated Using Amyloid β1-42-Mediated in Vitro and in Vivo Alzheimer’s Disease Models. International Journal of Indigenous Medicinal Plants, 47, 1669-1682. [7] Marvin (2011) Marvin Was Used for Drawing, Displaying and Characterizing Chemical Structures, Substructures and Reactions, Marvin 5.7. [8] Thomsen, R. and Christensen, M.H. (2006) MolDock: A New Technique for High-Accuracy Molecular Docking. Journal of Medicinal Chemistry, 49, 3315-3321. http://dx.doi.org/10.1021/jm051197e [9] Lührs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Döbeli, H., Schubert, D. and Riek, R. (2005) 3D Structure of Alzheimer’s Amyloid-Beta (1-42) Fibrils. roceedings of the National Academy of Sciences of the United States of America, 102, 17342-17347. http://dx.doi.org/10.1073/pnas.0506723102 [10] Lyskov, S. and Gray, J.J. (2008) The RosettaDock Server for Local Protein-Protein Docking. Nucleic Acids Research, 36, W233-W238. http://dx.doi.org/10.1093/nar/gkn216 [11] Duhovny, D., Nussinov, R. and Wolfson, H.J. (2002) Efficient Unbound Docking of Rigid Molecules. In: Guigó, R. and Gusfield, D., Eds., Proceedings of the 2nd Workshop on Algorithms in Bioinformatics (WABI) Rome, Italy, Lecture Notes in Computer Science (LNCS) 2452, Springer Verlag, Berlin Heidelberg, 185-200. [12] Hossain, S., Hashimoto, M., Katakura, M., Miwa, K., Shimada, T. and Shido, O. (2009) Mechanism of Docosahexaenoic Acid-Induced Inhibition of in Vitro Aβ1-42 Fibrillation and Aβ1-42-Induced Toxicity in SH-S5Y5 Cells. Journal of Neurochemistry, 111, 568-579.
http://dx.doi.org/10.1111/j.1471-4159.2009.06336.x [13] Hashimoto, M., Hossain, S., Yamashita, S., Katakura, M., Tanabe, Y., Fujiwara, H., Gamoh, S., Miyazawa, T., Arai, H., Shimada, T. and Shido, O. (2008) Docosahexaenoic Acid Disrupts in Vitro Amyloid β1-40 Fibrillation and Concomitantly Inhibits Amyloid Levels in Cerebral Cortex of Alzheimer’s Disease Model Rats. Journal of Neurochemistry, 107, 1634-1646. http://dx.doi.org/10.1111/j.1471-4159.2008.05731.x [14] Hashimoto, M., Hossain, S., Katakura, M., Mamun, A.A. and Shido, O. (2015) The Binding of Aβ1-42 to Lipid Rafts of RBC Is Enhanced by Dietary Docosahexaenoic Acid in Rats: Implicates to Alzheimer’s Disease. Biochimica et Biophysica Acta, 1848, 1402-1409. http://dx.doi.org/10.1016/j.bbamem.2015.03.008 [15] Hashimoto, M., Hossain, S., Hossain, S., Rahman, A., Shimada, T. and Shido, O. (2011) Docosahexaenoic Acid Withstands the Aβ25-35-Induced Neurotoxicity in SH-SY5Y Cells. The Journal of Nutritional Biochemistry, 22, 22-29. http://dx.doi.org/10.1016/j.jnutbio.2009.11.005 [16] Groenning, M. (2009) Binding Mode of Thioflavin T and Other Molecular Probes in the Context of Amyloid Fibrils- Current Status. Journal of Chemical Biology, 3, 1-18.
http://dx.doi.org/10.1007/s12154-009-0027-5 [17] Kim, Y., Lee, J.H., Ryu, J. and Kim, D.J. (2009) Multivalent & Multifunctional Ligands to Beta-Amyloid. Current Pharmaceutical Design, 15, 637-658. http://dx.doi.org/10.2174/138161209787315648 [18] Nilsson, K.P. (2009) Small Organic Probes as Amyloid Specific Ligands-Past and Recent Molecular Scaffolds. FEBS Letters, 583, 2593-2599. http://dx.doi.org/10.1016/j.febslet.2009.04.016 [19] Hossain, S., Hashimoto, M., Katakura, M., Mamun, A.A. and Shido, O. (2015) Medicinal Value of Asiaticoside for Alzheimer’s Disease as Assessed Using Single-Molecule-Detection Fluorescence Correlation Spectroscopy, Laser- Scanning Microscopy, Transmission Electron Microscopy, and in Silico Docking. BMC Complementary and Alternative Medicine, 15, in Press. http://dx.doi.org/10.1186/s12906-015-0620-9 [20] Sirk, T.W., Friedman, M. and Brown, E.F. (2011) Molecular Binding of Black Tea Theaflavins to Biological Membranes: Relationship to Bioactivities. Journal of Agricultural and Food Chemistry, 59, 3780-3787.
http://dx.doi.org/10.1021/jf2006547 [21] Stefani, M.S. (2013) Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds. International Journal of Molecular Sciences, 14, 12411-12457.
http://dx.doi.org/10.3390/ijms140612411