Inhibition of Glutamate Release from Rat Cortical Nerve Terminals by Dehydrocorydaline, an Alkaloid from Corydalis yanhusuo

Abstract

Excessive release of glutamate induces excitotoxicity and causes neuronal damage in several neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for preventing and treating neurological disorders. Dehydrocorydaline (DHC), an active alkaloid compound isolated from Corydalis yanhusuo, possesses neuroprotective capacity. The present study investigated the effect of DHC on glutamate release using a rat brain cortical synaptosome model. Our results indicate that DHC inhibited 4-aminopyridine (4-AP)-evoked glutamate release and elevated intrasynaptosomal calcium levels. The inhibitory effect of DHC on 4-AP-evoked glutamate release was prevented in the presence of the vesicular transporter inhibitor bafilomycin A1 and the N- and P/Q-type Ca2+ channel blocker ω-conotoxin MVIIC but not the intracellular inhibitor of Ca2+ release dantrolene or the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157. Moreover, the inhibitory effect of DHC on evoked glutamate release was prevented by the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) inhibitor PD98059. Western blotting data in synaptosomes also showed that DHC significantly decreased the level of ERK1/2 phosphorylation and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. Together, these results suggest that DHC inhibits presynaptic glutamate release from cerebrocortical synaptosomes by suppressing presynaptic voltage-dependent Ca2+ entry and the MAPK/ERK/synapsin I signaling pathway.

Network Pharmacology and Experimental Verification to Unveil the Mechanism of N-Methyl-D-Aspartic Acid Rescue Humantenirine-Induced Excitotoxicity

“…MAPK3 and MAPK1 are the core members of the MAPK family, which play crucial roles in the signal transduction cascade by regulating various cellular processes. The activation of ERK 1/2 can regulate the activity of NMDA receptors by affecting the release of glutamate from synaptosomes, which leads to epilepsy [ 28 , 29 , 30 , 31 ]. NMDAR is involved in excitotoxicity and neuronal death under many pathological conditions [ 32 , 33 ].…”

Screening of the active Ingredients in Huanglian Jiedu decoction through amide bond-Immobilized magnetic nanoparticle-assisted cell membrane chromatography

“…Among the specific binding components, groenlandicine, berberrubine, worenine, dehydrocorydaline, baicalin, oroxylin A-7-O-β-D-glucuronide, and wogonoside significantly reduced glutamate-induced cell damage. Groenlandicine (Jung et al, 2009), dehydrocorydaline (Li et al, 2021;Lin et al, 2022), baicalin (Chen et al, 2015;Ding et al, 2015;Zhao et al, 2018;Yu et al, 2022), and wogonoside (Yang et al, 2014) have been reported to have neuroprotective effects against excitotoxic cell death. Herein, the protective effects of berberrubine, worenine, and oroxylin A-7-Oβ-D-glucuronide in oxidative stress injuries have been reported for the first time to the best of our knowledge.…”

Plantainoside D Reduces Depolarization-Evoked Glutamate Release from Rat Cerebral Cortical Synaptosomes

“…Glutamate release from purified prefrontal cortical synaptosomes was monitored online with an assay that employed exogenous GDH and NADP + to couple the oxidative deamination of the released glutamate to the generation of NADPH detected fluorometrically [ 49 ]. A 2 mL aliquot of synaptosomes (0.5 mg of protein) was transferred to a cuvette maintained at 37 °C and stirred with a magnetic bar.…”

“…Western blotting was performed according to the standard procedures [ 49 ]. RIPA buffer mixed with protease and phosphatase inhibitors (Thermo Fisher Scientific, Waltham, MA, USA) was used to prepare protein extracts.…”