Abstract
In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.
Highlights
Neurodegenerative diseases have no treatment currently available, and the principal goals for neurodegeneration care are early diagnosis, physical health, optimizing, identifying and treating abnormal behavioral and psychological symptoms
The presence of excessive glutamate triggers Reactive oxygen species (ROS), an increase in intracellular calcium ion concentration, and the activation of Mitogen-activated protein kinases (MAPKs), including phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38, which are responsible for neuronal cell death in both primary neuronal cultures and neuronal cell lines [13]
We confirmed the antioxidant activity of THC through an in vitro 1,1-diphenyl-picryl hydrazyl (DPPH) radical scavenging assay, which is used to evaluate the antioxidant effects
Summary
Neurodegenerative diseases have no treatment currently available, and the principal goals for neurodegeneration care are early diagnosis, physical health, optimizing, identifying and treating abnormal behavioral and psychological symptoms. Phenolic compounds from natural sources exhibit various beneficial effects in cancer, inflammation, and neurodegenerative disorders [9] This broad spectrum of biological or pharmacological activities has made phytochemicals suitable candidates for treating multifactorial diseases, such as neurodegenerative diseases [10,11]. Mitogen-activated protein kinases (MAPKs), known as a family of serine/threonine protein kinases, are well-identified biological molecules involved in glutamate-induced oxidative neuronal cell death. The presence of excessive glutamate triggers ROS, an increase in intracellular calcium ion concentration, and the activation of MAPKs, including phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38, which are responsible for neuronal cell death in both primary neuronal cultures and neuronal cell lines [13]. The present study was carried out to demonstrate the possible effect and the protective mechanism of THC on glutamate-mediated neuronal cell death
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