In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing
Chronic wound resulting from diabetes mellitus is a significant cause of amputation worldwide. Secondary infections, lowering of nitric oxide synthase level, reduction of glucose-6-phosphate dehydrogenase levels, improper extracellular matrix remodelling, neuropathy, abnormality of endothelial cell...
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MDPI AG
2023-03-01
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| Online Access: | https://www.mdpi.com/2673-9992/21/1/21 |
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| author | Ankit Majie Rajdeep Saha Biswatrish Sarkar |
| author_facet | Ankit Majie Rajdeep Saha Biswatrish Sarkar |
| author_sort | Ankit Majie |
| collection | DOAJ |
| description | Chronic wound resulting from diabetes mellitus is a significant cause of amputation worldwide. Secondary infections, lowering of nitric oxide synthase level, reduction of glucose-6-phosphate dehydrogenase levels, improper extracellular matrix remodelling, neuropathy, abnormality of endothelial cell function, and vasculopathy impedes the normal wound healing cycle during diabetes. Multiple studies have concluded that Ser9 phosphorylation causes inhibition of the glycogen synthase kinase-3β (GSK3-β) protein, which is essential for faster diabetic wound healing. Hence this protein could be a potential target for molecular interactions with prospective wound-healing molecules. Verbascoside, martynoside, echinacoside, crenatoside, and salidroside are a few phenylethanoid glycosides that have potential wound-healing ability by increasing extracellular matrix synthesis, angiogenesis, keratinocyte migration, and the functioning of macrophages and neutrophils. Thus, the five glycosides were subjected to molecular docking with GSK3-β protein (PDB ID: 1I09). This study revealed strong binding interactions with GSK3-β (between −10.2 and −7.3 kcal/mol) and inhibition constants (between 0.032 and 4.397 µM) which suggested potent inhibition of the target protein even at lower concentrations of these compounds. Further, the docked complexes were visualized to find the interaction of the ligands with the amino acid residues. However, further in vivo and in vitro studies are required to validate the activity of these phenylpropanoid glycosides in diabetic wound healing. |
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| language | English |
| last_indexed | 2024-03-08T20:28:58Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-6053310bcd4741eb8e0e9dadb4a29c8e2023-12-22T14:28:42ZengMDPI AGMedical Sciences Forum2673-99922023-03-012112110.3390/ECB2023-14134In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound HealingAnkit Majie0Rajdeep Saha1Biswatrish Sarkar2Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, IndiaDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, IndiaDepartment of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, IndiaChronic wound resulting from diabetes mellitus is a significant cause of amputation worldwide. Secondary infections, lowering of nitric oxide synthase level, reduction of glucose-6-phosphate dehydrogenase levels, improper extracellular matrix remodelling, neuropathy, abnormality of endothelial cell function, and vasculopathy impedes the normal wound healing cycle during diabetes. Multiple studies have concluded that Ser9 phosphorylation causes inhibition of the glycogen synthase kinase-3β (GSK3-β) protein, which is essential for faster diabetic wound healing. Hence this protein could be a potential target for molecular interactions with prospective wound-healing molecules. Verbascoside, martynoside, echinacoside, crenatoside, and salidroside are a few phenylethanoid glycosides that have potential wound-healing ability by increasing extracellular matrix synthesis, angiogenesis, keratinocyte migration, and the functioning of macrophages and neutrophils. Thus, the five glycosides were subjected to molecular docking with GSK3-β protein (PDB ID: 1I09). This study revealed strong binding interactions with GSK3-β (between −10.2 and −7.3 kcal/mol) and inhibition constants (between 0.032 and 4.397 µM) which suggested potent inhibition of the target protein even at lower concentrations of these compounds. Further, the docked complexes were visualized to find the interaction of the ligands with the amino acid residues. However, further in vivo and in vitro studies are required to validate the activity of these phenylpropanoid glycosides in diabetic wound healing.https://www.mdpi.com/2673-9992/21/1/21phenylpropanoid glycosidesdiabetes mellituswound healingbinding interactionsinhibition constants |
| spellingShingle | Ankit Majie Rajdeep Saha Biswatrish Sarkar In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing Medical Sciences Forum phenylpropanoid glycosides diabetes mellitus wound healing binding interactions inhibition constants |
| title | In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing |
| title_full | In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing |
| title_fullStr | In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing |
| title_full_unstemmed | In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing |
| title_short | In Silico Study to Evaluate the Inhibitory Activity of a Few Phenylethanoid Glycosides on GSK3-β Protein for Faster Diabetic Wound Healing |
| title_sort | in silico study to evaluate the inhibitory activity of a few phenylethanoid glycosides on gsk3 β protein for faster diabetic wound healing |
| topic | phenylpropanoid glycosides diabetes mellitus wound healing binding interactions inhibition constants |
| url | https://www.mdpi.com/2673-9992/21/1/21 |
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