Cargando…
Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model
Clinical evidence suggests that type 2 diabetes therapy can greatly benefit from the suppression of reactive oxygen species generation and the activation or restoration of cellular antioxidant mechanisms. In human, NADPH oxidase (NOX) is the main producer of reactive oxygen species (ROS) that supres...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809395/ https://www.ncbi.nlm.nih.gov/pubmed/33490651 http://dx.doi.org/10.1016/j.bbrep.2020.100904 |
_version_ | 1783637112623464448 |
---|---|
author | Mazumdar, Suchismita Marar, Thankamani Devarajan, Shine Patki, Jyoti |
author_facet | Mazumdar, Suchismita Marar, Thankamani Devarajan, Shine Patki, Jyoti |
author_sort | Mazumdar, Suchismita |
collection | PubMed |
description | Clinical evidence suggests that type 2 diabetes therapy can greatly benefit from the suppression of reactive oxygen species generation and the activation or restoration of cellular antioxidant mechanisms. In human, NADPH oxidase (NOX) is the main producer of reactive oxygen species (ROS) that supress the activity of endogenous antioxidant enzymes. In the present study, the antioxidant potential of Gedunin was studied. In silico findings reveal its strong binding affinity with NOX5 C terminal HSP90 binding site that disrupts NOX5 stability and its ability to generate ROS, leading to restoration antioxidant enzymes activities. It was found that Gedunin suppressed hyperglycaemia induced oxidative stress in an in vitro RBC model and markedly reversed glucose induced changes including haemoglobin glycosylation and lipid peroxidation. A significant restoration of activities of cellular antioxidant enzymes; superoxide dismutase, catalase and glutathione peroxidase in the presence of Gedunin revealed its ability to reduce oxidative stress. These results substantiated Gedunin as a bona fide inhibitor of human NOX5 and a ROS scavenging antioxidant with promising therapeutic attributes including its natural origin and inhibition of multiple diabetic targets. |
format | Online Article Text |
id | pubmed-7809395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78093952021-01-22 Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model Mazumdar, Suchismita Marar, Thankamani Devarajan, Shine Patki, Jyoti Biochem Biophys Rep Research Article Clinical evidence suggests that type 2 diabetes therapy can greatly benefit from the suppression of reactive oxygen species generation and the activation or restoration of cellular antioxidant mechanisms. In human, NADPH oxidase (NOX) is the main producer of reactive oxygen species (ROS) that supress the activity of endogenous antioxidant enzymes. In the present study, the antioxidant potential of Gedunin was studied. In silico findings reveal its strong binding affinity with NOX5 C terminal HSP90 binding site that disrupts NOX5 stability and its ability to generate ROS, leading to restoration antioxidant enzymes activities. It was found that Gedunin suppressed hyperglycaemia induced oxidative stress in an in vitro RBC model and markedly reversed glucose induced changes including haemoglobin glycosylation and lipid peroxidation. A significant restoration of activities of cellular antioxidant enzymes; superoxide dismutase, catalase and glutathione peroxidase in the presence of Gedunin revealed its ability to reduce oxidative stress. These results substantiated Gedunin as a bona fide inhibitor of human NOX5 and a ROS scavenging antioxidant with promising therapeutic attributes including its natural origin and inhibition of multiple diabetic targets. Elsevier 2021-01-07 /pmc/articles/PMC7809395/ /pubmed/33490651 http://dx.doi.org/10.1016/j.bbrep.2020.100904 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Mazumdar, Suchismita Marar, Thankamani Devarajan, Shine Patki, Jyoti Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model |
title | Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model |
title_full | Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model |
title_fullStr | Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model |
title_full_unstemmed | Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model |
title_short | Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model |
title_sort | functional relevance of gedunin as a bona fide ligand of nadph oxidase 5 and ros scavenger: an in silico and in vitro assessment in a hyperglycemic rbc model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809395/ https://www.ncbi.nlm.nih.gov/pubmed/33490651 http://dx.doi.org/10.1016/j.bbrep.2020.100904 |
work_keys_str_mv | AT mazumdarsuchismita functionalrelevanceofgeduninasabonafideligandofnadphoxidase5androsscavengeraninsilicoandinvitroassessmentinahyperglycemicrbcmodel AT mararthankamani functionalrelevanceofgeduninasabonafideligandofnadphoxidase5androsscavengeraninsilicoandinvitroassessmentinahyperglycemicrbcmodel AT devarajanshine functionalrelevanceofgeduninasabonafideligandofnadphoxidase5androsscavengeraninsilicoandinvitroassessmentinahyperglycemicrbcmodel AT patkijyoti functionalrelevanceofgeduninasabonafideligandofnadphoxidase5androsscavengeraninsilicoandinvitroassessmentinahyperglycemicrbcmodel |