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Accelerated identification of serine racemase inhibitor from Centella asiatica.

Scientific reports (2020-03-15)
Komal Rani, Mitali Tyagi, Mohit Mazumder, Akanksha Singh, Annaian Shanmugam, Krishna Dalal, Manoj Pillai, Gourinath Samudrala, Saroj Kumar, Alagiri Srinivasan
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Madecassoside from Centella asiatica, ≥95% (HPLC)
Sigma-Aldrich
Anti-D-Serine Antibody, serum, Chemicon®