Abstract
Rosmarinic acid, a major component of rosemary, is a polyphenolic compound with potential neuroprotective effects. Asreducing the synaptic release of glutamate is crucial to achieving neuroprotectant’s pharmacotherapeutic effects, the effect of rosmarinic acid on glutamate release was investigated in rat cerebrocortical nerve terminals (synaptosomes). Rosmarinic acid depressed the 4-aminopyridine (4-AP)-induced glutamate release in a concentration-dependent manner. The removal of extracellular calcium and the blockade of vesicular transporters prevented the inhibition of glutamate release by rosmarinic acid. Rosmarinic acid reduced 4-AP-induced intrasynaptosomal Ca2+ elevation. The inhibition of N-, P/Q-type Ca2+ channels and the calcium/calmodulin-dependent kinase II (CaMKII) prevented rosmarinic acid from having effects on glutamate release. Rosmarinic acid also reduced the 4-AP-induced activation of CaMKII and the subsequent phosphorylation of synapsin I, the main presynaptic target of CaMKII. In addition, immunocytochemistry confirmed the presence of GABAA receptors. GABAA receptor agonist and antagonist blocked the inhibitory effect of rosmarinic acid on 4-AP-evoked glutamate release. Docking data also revealed that rosmarinic acid formed a hydrogen bond with the amino acid residues of GABAA receptor. These results suggested that rosmarinic acid activates GABAA receptors in cerebrocortical synaptosomes to decrease Ca2+ influx and CaMKII/synapsin I pathway to inhibit the evoked glutamate release.
Highlights
Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS)and acts through glutamate receptors to modulate synaptic transmission
Rosmarinic acid inhibited the 4-AP-evoked phosphorylation of calmodulin-dependent kinase II (CaMKII) and synapsin I. These results suggest that the suppression of CaMKII activity and the inhibition of synapsin I phosphorylation is involved in the rosmarinic acid-mediated inhibition of glutamate release
Our results demonstrate for the first time that rosmarinic acid, through
Summary
Acts through glutamate receptors to modulate synaptic transmission. Entry into neurons, protease activation, mitochondrial damage, free radical generation, and neuronal death [2,3]. This process, known as excitotoxicity, is the mechanism underlying numerous CNS diseases [4,5]. Modulating synaptic glutamate release is a valuable strategy for reducing neurotoxicity and protecting the brain [6,7,8]. Plant-derived compounds have received considerable attention for their neuroprotective activities [9,10]. Rosemary (Rosmarinus officinalis L.), a common household plant, is a Biomolecules 2021, 11, 1029.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
