Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Sci Rep. 2020 Mar 13;10(1):4640. doi: 10.1038/s41598-020-61494-1.
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.
丝氨酸消旋酶（SR）在哺乳动物大脑中将游离形式的 L-丝氨酸转化为 D-丝氨酸（DS）。DS 作为 N-甲基-D-天冬氨酸（NMDA）受体的共激动剂发挥作用。NMDA 受体的过度激活会导致许多神经疾病，如中风、肌萎缩侧索硬化症、阿尔茨海默病，而 SR 的有效抑制剂可能是纠正受体过度激活的一种方法。我们首次在这里报告了一种从具有神经保护作用的药用植物中快速纯化和鉴定抑制剂的方法。我们已经通过亲和方法从积雪草的甲醇提取物中纯化出 SR 抑制剂。高分辨率质谱和红外光谱用于鉴定配体为积雪草酸。我们已经在计算机中显示了积雪草酸的结合及其对重组人丝氨酸消旋酶的体外和离体抑制作用。
