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Accelerated identification of serine racemase inhibitor from Centella asiatica

Serine racemase (SR) converts the free form of L-serine into D-serine (DS) in the mammalian brain. The DS functions as a co-agonist of N-methyl D-aspartate (NMDA) receptor. The over- activation of NMDA receptor leads to many neurological disorders like stroke, amyotrophic lateral sclerosis, Alzheime...

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Autores principales: Rani, Komal, Tyagi, Mitali, Mazumder, Mohit, Singh, Akanksha, Shanmugam, Annaian, Dalal, Krishna, Pillai, Manoj, Samudrala, Gourinath, Kumar, Saroj, Srinivasan, Alagiri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070078/
https://www.ncbi.nlm.nih.gov/pubmed/32170206
http://dx.doi.org/10.1038/s41598-020-61494-1
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author Rani, Komal
Tyagi, Mitali
Mazumder, Mohit
Singh, Akanksha
Shanmugam, Annaian
Dalal, Krishna
Pillai, Manoj
Samudrala, Gourinath
Kumar, Saroj
Srinivasan, Alagiri
author_facet Rani, Komal
Tyagi, Mitali
Mazumder, Mohit
Singh, Akanksha
Shanmugam, Annaian
Dalal, Krishna
Pillai, Manoj
Samudrala, Gourinath
Kumar, Saroj
Srinivasan, Alagiri
author_sort Rani, Komal
collection PubMed
description Serine racemase (SR) converts the free form of L-serine into D-serine (DS) in the mammalian brain. The DS functions as a co-agonist of N-methyl D-aspartate (NMDA) receptor. The over- activation of NMDA receptor leads to many neurological disorders like stroke, amyotrophic lateral sclerosis, Alzheimer’s disease and an effective inhibitor of SR could be a corrective method for the receptor over-activation. We report for the first time here a rapid way of purifying and identifying an inhibitor from medicinal plants known to have the neuro-protective effect. We have purified SR inhibitor from the methanolic extract of Centella asiatica by affinity method. High resolution mass spectrometry and infrared spectroscopy were used to identify the ligand to be madecassoside. We have shown the madecassoside binding in silico and its inhibition of recombinant human serine racemase in vitro and ex vivo.
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spelling pubmed-70700782020-03-22 Accelerated identification of serine racemase inhibitor from Centella asiatica Rani, Komal Tyagi, Mitali Mazumder, Mohit Singh, Akanksha Shanmugam, Annaian Dalal, Krishna Pillai, Manoj Samudrala, Gourinath Kumar, Saroj Srinivasan, Alagiri Sci Rep Article Serine racemase (SR) converts the free form of L-serine into D-serine (DS) in the mammalian brain. The DS functions as a co-agonist of N-methyl D-aspartate (NMDA) receptor. The over- activation of NMDA receptor leads to many neurological disorders like stroke, amyotrophic lateral sclerosis, Alzheimer’s disease and an effective inhibitor of SR could be a corrective method for the receptor over-activation. We report for the first time here a rapid way of purifying and identifying an inhibitor from medicinal plants known to have the neuro-protective effect. We have purified SR inhibitor from the methanolic extract of Centella asiatica by affinity method. High resolution mass spectrometry and infrared spectroscopy were used to identify the ligand to be madecassoside. We have shown the madecassoside binding in silico and its inhibition of recombinant human serine racemase in vitro and ex vivo. Nature Publishing Group UK 2020-03-13 /pmc/articles/PMC7070078/ /pubmed/32170206 http://dx.doi.org/10.1038/s41598-020-61494-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Rani, Komal
Tyagi, Mitali
Mazumder, Mohit
Singh, Akanksha
Shanmugam, Annaian
Dalal, Krishna
Pillai, Manoj
Samudrala, Gourinath
Kumar, Saroj
Srinivasan, Alagiri
Accelerated identification of serine racemase inhibitor from Centella asiatica
title Accelerated identification of serine racemase inhibitor from Centella asiatica
title_full Accelerated identification of serine racemase inhibitor from Centella asiatica
title_fullStr Accelerated identification of serine racemase inhibitor from Centella asiatica
title_full_unstemmed Accelerated identification of serine racemase inhibitor from Centella asiatica
title_short Accelerated identification of serine racemase inhibitor from Centella asiatica
title_sort accelerated identification of serine racemase inhibitor from centella asiatica
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070078/
https://www.ncbi.nlm.nih.gov/pubmed/32170206
http://dx.doi.org/10.1038/s41598-020-61494-1
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