Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods
The inhibition of glycogen synthase kinase-3β (GSK-3β) activity prevents tau hyperphosphorylation and binds it to the microtubule network. Therefore, a GSK-3β inhibitor may be a recommended drug for Alzheimer’s treatment. In silico methods are currently considered as one of the fastest and most cost...
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2021.709932/full |
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| author | Marzieh Eskandarzadeh Parastou Kordestani-Moghadam Saeed Pourmand Javad Khalili Fard Javad Khalili Fard Bijan Almassian Sajjad Gharaghani |
| author_facet | Marzieh Eskandarzadeh Parastou Kordestani-Moghadam Saeed Pourmand Javad Khalili Fard Javad Khalili Fard Bijan Almassian Sajjad Gharaghani |
| author_sort | Marzieh Eskandarzadeh |
| collection | DOAJ |
| description | The inhibition of glycogen synthase kinase-3β (GSK-3β) activity prevents tau hyperphosphorylation and binds it to the microtubule network. Therefore, a GSK-3β inhibitor may be a recommended drug for Alzheimer’s treatment. In silico methods are currently considered as one of the fastest and most cost-effective available alternatives for drug/design discovery in the field of treatment. In this study, computational drug design was conducted to introduce compounds that play an effective role in inhibiting the GSK-3β enzyme by molecular docking and molecular dynamics simulation. The iridoid glycosides of the common snowberry (Symphoricarpos albus), including loganin, secologanin, and loganetin, are compounds that have an effect on improving memory and cognitive impairment and the results of which on Alzheimer’s have been studied as well. In this study, in the molecular docking phase, loganin was considered a more potent inhibitor of this protein by establishing a hydrogen bond with the ATP-binding site of GSK-3β protein and the most negative binding energy to secologanin and loganetin. Moreover, by molecular dynamics simulation of these ligands and GSK-3β protein, all structures were found to be stable during the simulation. In addition, the protein structure represented no change and remained stable by binding ligands to GSK-3β protein. Furthermore, loganin and loganetin have higher binding free energy than secologanin; thus, these compounds could effectively bind to the active site of GSK-3β protein. Hence, loganin and loganetin as iridoid glycosides can be effective in Alzheimer’s prevention and treatment, and thus, further in vitro and in vivo studies can focus on these iridoid glycosides as an alternative treatment. |
| first_indexed | 2024-12-14T06:16:24Z |
| format | Article |
| id | doaj.art-767a747bf18a492ea7aea37d26061854 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-14T06:16:24Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-767a747bf18a492ea7aea37d260618542022-12-21T23:14:01ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-10-01910.3389/fchem.2021.709932709932Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design MethodsMarzieh Eskandarzadeh0Parastou Kordestani-Moghadam1Saeed Pourmand2Javad Khalili Fard3Javad Khalili Fard4Bijan Almassian5Sajjad Gharaghani6Research Committee of Faculty of Pharmacy, Lorestan University of Medical Science, Khorramabad, IranSocial Determinants of Health Research Center, Lorestan University of Medical Sciences, Khorramabad, IranDepartment of Chemical Engineering, Faculty of Chemical and Petroleum Engineering, University of Tabriz, Tabriz, IranRazi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, IranDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranCaroGen Corporation, Farmington, CT, United StatesLaboratory of Bioinformatics and Drug Design, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, IranThe inhibition of glycogen synthase kinase-3β (GSK-3β) activity prevents tau hyperphosphorylation and binds it to the microtubule network. Therefore, a GSK-3β inhibitor may be a recommended drug for Alzheimer’s treatment. In silico methods are currently considered as one of the fastest and most cost-effective available alternatives for drug/design discovery in the field of treatment. In this study, computational drug design was conducted to introduce compounds that play an effective role in inhibiting the GSK-3β enzyme by molecular docking and molecular dynamics simulation. The iridoid glycosides of the common snowberry (Symphoricarpos albus), including loganin, secologanin, and loganetin, are compounds that have an effect on improving memory and cognitive impairment and the results of which on Alzheimer’s have been studied as well. In this study, in the molecular docking phase, loganin was considered a more potent inhibitor of this protein by establishing a hydrogen bond with the ATP-binding site of GSK-3β protein and the most negative binding energy to secologanin and loganetin. Moreover, by molecular dynamics simulation of these ligands and GSK-3β protein, all structures were found to be stable during the simulation. In addition, the protein structure represented no change and remained stable by binding ligands to GSK-3β protein. Furthermore, loganin and loganetin have higher binding free energy than secologanin; thus, these compounds could effectively bind to the active site of GSK-3β protein. Hence, loganin and loganetin as iridoid glycosides can be effective in Alzheimer’s prevention and treatment, and thus, further in vitro and in vivo studies can focus on these iridoid glycosides as an alternative treatment.https://www.frontiersin.org/articles/10.3389/fchem.2021.709932/fullloganinAlzheimer’s diseaseGSK_3 betadockingSymphoricarpos |
| spellingShingle | Marzieh Eskandarzadeh Parastou Kordestani-Moghadam Saeed Pourmand Javad Khalili Fard Javad Khalili Fard Bijan Almassian Sajjad Gharaghani Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods Frontiers in Chemistry loganin Alzheimer’s disease GSK_3 beta docking Symphoricarpos |
| title | Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods |
| title_full | Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods |
| title_fullStr | Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods |
| title_full_unstemmed | Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods |
| title_short | Inhibition of GSK_3β by Iridoid Glycosides of Snowberry (Symphoricarpos albus) Effective in the Treatment of Alzheimer’s Disease Using Computational Drug Design Methods |
| title_sort | inhibition of gsk 3β by iridoid glycosides of snowberry symphoricarpos albus effective in the treatment of alzheimer s disease using computational drug design methods |
| topic | loganin Alzheimer’s disease GSK_3 beta docking Symphoricarpos |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2021.709932/full |
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