Abstract
Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 μM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.
Highlights
Neurological disorders are a major public health problem that constitutes more than6% of the global burden of disease [1]
These results suggest that OAC could be a promising neuroprotective
These results suggest that OAC could be a promising neuroprotective agent
Summary
Neurological disorders are a major public health problem that constitutes more than6% of the global burden of disease [1]. 45.9 million people worldwide were estimated to have epilepsy in 2016, and 1 in 10 individuals has suffered from at least one epileptic seizure in their lifetime [2]. Dementia was found to affect 47 million people globally in 2015, with AD contributing to 60–70% of cases [3]. The main pathogenesis mechanism of neurological disorders is the abnormality or death of brain cells caused by excitotoxic effects, disturbance of cellular energy metabolism, and oxidative stress [4]. If the concentration of intracellular ROS or RNS exceeds the limitation of the antioxidant barrier of biological systems, it will cause oxidative stress, leading to apoptotic and necrotic cell death [6,7].
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
