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

• Published in: Phytotherapy research Vol. 35; no. 6; pp. 3377 - 3389
• Main Authors: Zheng, Xing Xing, Li, Ying Chun, Yang, Kai Lin, He, Zhou Xiao, Wang, Zhao Liang, Wang, Xing, Jing, Hui Ling, Cao, Yan Jun
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.06.2021; Wiley Subscription Services, Inc
• Subjects: Apoptosis; BAX protein; Calcium (intracellular); Calcium ions; Caspase; Cell viability; Cholecystokinin; Evaluation; Excitotoxicity; Flow cytometry; Fluorescent indicators; glutamate; Herbal medicine; Icariin; Intracellular; Membrane potential; Membranes; Mitochondria; NADPH oxidase; Neurological diseases; Neurotoxicity; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Reactive oxygen species; SH‐SY5Y; Toxicity; Western blotting; Icariin; SH-SY5Y; apoptosis; excitotoxicity; NADPH oxidase; glutamate
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.7057

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. Highlights Icariin (ICA) protected against excitatory neurotoxicity in SH‐SY5Y cells exposed to glutamate (Glu). ICA significantly reduced apoptosis and inhibited the increase of mitochondrial membrane potential in Glu‐induced SH‐SY5Y cells. ICA significantly decreased apoptosis through NADPH oxidase and Bax/Bcl‐2 pathway in SH‐SY5Y cells exposed to Glu.