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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 Ca 2+ 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 Ca 2+ 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.

Titel:	Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells.
Autor/in / Beteiligte Person:	Zheng, XX ; Li, YC ; Yang, KL ; He, ZX ; Wang, ZL ; Wang, X ; Jing, HL ; Cao, YJ
Link:	Zum Volltext
Zeitschrift:	Phytotherapy research : PTR, Jg. 35 (2021-06-01), Heft 6, S. 3377-3389
Veröffentlichung:	<June 1990-> : Chichester : Wiley ; <i>Original Publication</i>: London : Heyden & Son, c1987-, 2021
Medientyp:	academicJournal
ISSN:	1099-1573 (electronic)
DOI:	10.1002/ptr.7057
Schlagwort:	Caspase 3 metabolism Cell Line, Tumor Cell Survival drug effects Glutamic Acid pharmacology Humans Membrane Potential, Mitochondrial drug effects Nitric Oxide Synthase Type II metabolism Proto-Oncogene Proteins c-bcl-2 metabolism Reactive Oxygen Species metabolism Antioxidants pharmacology Apoptosis drug effects Flavonoids pharmacology Oxidative Stress drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Phytother Res] 2021 Jun; Vol. 35 (6), pp. 3377-3389. <i>Date of Electronic Publication: </i>2021 Apr 23. MeSH Terms: Antioxidants / pharmacology ; Apoptosis / drug effects ; Flavonoids / pharmacology ; Oxidative Stress / drug effects ; Caspase 3 / metabolism ; Cell Line, Tumor ; Cell Survival / drug effects ; Glutamic Acid / pharmacology ; Humans ; Membrane Potential, Mitochondrial / drug effects ; Nitric Oxide Synthase Type II / metabolism ; Proto-Oncogene Proteins c-bcl-2 / metabolism ; Reactive Oxygen Species / metabolism References: Albrecht, P., Lewerenz, J., Dittmer, S., Noack, R., Maher, P., & Methner, A. (2010). Mechanisms of oxidative glutamate toxicity: The glutamate/cyctine antiporter system xc-as a neuroprotective drug target. CNS & Neurological Disorders Drug Targets, 9, 373-382. ; Bhat, A. H., Dar, K. B., Anees, S., Zargar, M. A., Masood, A., Sofi, M. 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Grant Information: 31600822 National Natural Science Foundation of China; 81773870 National Natural Science Foundation of China; 2020JM-440 Natural Science Foundation of Shaanxi Province; ZSK2019001 Open Fund for Key Laboratories of the Ministry of Education of Resources Biology and Modern Biotechnology in Western China; 2019324 The Educational Reform project and Student's Platform for Innovation and Entrepreneurship Training Program of China and Northwest University; 2019345 The Educational Reform project and Student's Platform for Innovation and Entrepreneurship Training Program of China and Northwest University; XM05191249 The Educational Reform project and Student's Platform for Innovation and Entrepreneurship Training Program of China and Northwest University Contributed Indexing: Keywords: Icariin; NADPH oxidase; SH-SY5Y; apoptosis; excitotoxicity; glutamate Substance Nomenclature: 0 (Antioxidants) ; 0 (BCL2 protein, human) ; 0 (Flavonoids) ; 0 (Proto-Oncogene Proteins c-bcl-2) ; 0 (Reactive Oxygen Species) ; 3KX376GY7L (Glutamic Acid) ; EC 1.14.13.39 (NOS2 protein, human) ; EC 1.14.13.39 (Nitric Oxide Synthase Type II) ; EC 3.4.22.- (CASP3 protein, human) ; EC 3.4.22.- (Caspase 3) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210423 Date Completed: 20210629 Latest Revision: 20210629 Update Code: 20240513

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