Icariin reduces Glu‐induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH‐SY5Y cells

Abstract

Excessive glutamate (Glu) can lead to significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades. Icariin (ICA) is a main active ingredient of Chinese Medicine Berberidaceae epimedium L., and has many biological activities, such as antiinflammation, antioxidative stress, and anti‐depression. This study aims to evaluate the effect of ICA on Glu‐induced excitatory neurotoxicity of SH‐SY5Y cells. The cell viability assay was evaluated by the CCK‐8 assay. The apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were assessed by flow cytometry. Intracellular Ca2+ concentration was determined by using the fluorescent probe Fluo‐3. Protein expression was detected by western blotting analysis. ICA can significantly enhance the SH‐SY5Y cell viability reduced by Glu. At the same time, ICA can significantly reduce apoptosis, ROS, nitric oxide (NO) levels, and intracellular Ca2+ concentration, and significantly inhibit the increase of mitochondrial membrane potential. In addition, ICA significantly increased the expression of P47phox and iNOS, decreased p‐JNK/JNK, p‐P38/P38, Bax/Bcl‐2, active caspase‐3, and active caspase‐9. These results indicate that ICA may reduce the excitatory neurotoxicity of Glu‐induced SH‐SY5Y cells through suppression of oxidative stress and apoptotic pathways, suggesting that ICA could be a potential therapeutic candidate for neurological disorders propagated by Glu toxicity.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry

“…EAAs participated in synaptic excitatory transmission and promoted learning and memory in physiological status. However, prolonged exposure to excessive EAAs can overly activate their receptors and evoke significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades [ 33 , 34 ] and increase sensitivity to excitotoxic injury. Therefore, the significant increase of glutamic acid and aspartic acid after stimulation might be one of the pathogenesis of aconitine neurotoxicity.…”

“…Similarly, efflux of glutamic acid and decreased intracellular glutamic acid could reduce GSH synthesis as well. GSH depletion leads to the accumulation of ROS and the consumption of SOD enzyme [ 12 , 27 , 33 , 39 ]. Our experimental results suggested that the intracellular Ca 2+ level of HT22 cells was significantly increased and the activity of Ca 2+ -ATPase was significantly inhibited after aconitine stimulation.…”

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

“…ICA has been revealed by many studies to play a crucial role in antioxidation ( Liu XJ. et al, 2021 ; Zheng et al, 2021 ) and anti-inflammatory ( Guangtao et al, 2021 ; Zhang et al, 2022 ). Hua et al found that IL-1β induces significant expression of COX-2 and iNOS and stimulates the production of PGE2 and nitric oxide in human NP cells ( Hua et al, 2018 ).…”

Icariin prevents depression-like behaviors in chronic unpredictable mild stress-induced rats through Bax/cytoplasm C/caspase-3 axis to alleviate neuronal apoptosis

“…In addition, ICA by inhibiting NF-κB signal activation and NLRP3-inflammasome/caspase-1/IL-1β axis plays an antidepressant-like role in CUMS model of depression in rats [26]. Otherwise, ICA reduces Glu-induced excitatory neurotoxicity through antioxidant and anti-apoptotic pathways in SH-SY5Y cells [27]. However, whether ICA is beneficial for the depression via ameliorating neuronal apoptosis in the hippocampus is still unknown.…”