PMID- 30119168 OWN - NLM STAT- MEDLINE DCOM- 20181126 LR - 20181126 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 106 DP - 2018 Oct TI - Aquilariae Lignum extract attenuates glutamate-induced neuroexcitotoxicity in HT22 hippocampal cells. PG - 1031-1038 LID - S0753-3322(18)32203-0 [pii] LID - 10.1016/j.biopha.2018.07.032 [doi] AB - An imbalance between excitatory and inhibitory neurotransmitters is known to induce neuronal excitotoxicity which is a major cause of neurodegenerative disorders. Excessive glutamate concentration leads to the neuronal death by increasing oxidative stress and affecting the apoptotic signaling pathway. We investigated the anti-excitotoxic effects and associated working mechanisms of 30% ethanol extract of Aquilariae Lignum (ALE) against hippocampal neuronal death by glutamate. HT22 cells were treated with glutamate (20 mM) for 24 h following pretreatment with ALE (5, 10, 25 mug/mL). Cell viability, biochemical analysis, flow chemistry, and Western blotting assays were performed. Glutamate treatment substantially increased the intracellular level of reactive oxygen species (ROS) and Ca(2+) influx into the cell, which were followed by apoptosis. ALE pretreatment, however, significantly attenuated these excitotoxicity-related features according to the results of Annexin V analysis and the lactate dehydrogenase assay, in which the calpain pathway (in a caspase 3-independent manner) may be involved. ALE pretreatment also significantly attenuated the glutamate-induced activation of both inflammation-associated molecules (extracellular signal-regulated kinase, c-Jun N-terminal kinases and p38) and death-related molecules (p53, apoptosis-inducing factor). The inactivation of brain-derived neurotrophic factor (BDNF) was restored by ALE pretreatment. Our results verified that A. Lignum has potential neuroprotective effects on glutamate-induced excitotoxicity in hippocampal neuron cells, and its underlying mechanism may involve the regulation of ROS-mediated cell death pathways. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Lee, Jin-Seok AU - Lee JS AD - Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, Republic of Korea. FAU - Kim, Won-Yong AU - Kim WY AD - Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, Republic of Korea. FAU - Jeon, Yoo-Jin AU - Jeon YJ AD - Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, Republic of Korea. FAU - Lee, Sam-Keun AU - Lee SK AD - Department of Applied Chemistry, Oriental Medicine Collage of Daejeon University, 62, Daehak-ro, Dong-gu, Daejeon, 300-716, Republic of Korea. FAU - Son, Chang-Gue AU - Son CG AD - Liver and Immunology Research Center, Oriental Medical Collage of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, Republic of Korea. Electronic address: ckson@dju.ac.kr. LA - eng PT - Journal Article DEP - 20180717 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Neuroprotective Agents) RN - 0 (Plant Extracts) RN - 0 (Reactive Oxygen Species) RN - 3KX376GY7L (Glutamic Acid) RN - EC 3.4.22.- (Calpain) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Calcium Signaling/drug effects MH - Calpain/metabolism MH - Cell Line MH - Dose-Response Relationship, Drug MH - Excitatory Amino Acid Agonists/*toxicity MH - Excitatory Amino Acid Antagonists/isolation & purification/*pharmacology MH - Glutamic Acid/*toxicity MH - Hippocampus/*drug effects/metabolism/pathology MH - Mice MH - Neurons/*drug effects/metabolism/pathology MH - Neuroprotective Agents/isolation & purification/*pharmacology MH - Phytotherapy MH - Plant Extracts/isolation & purification/*pharmacology MH - Plants, Medicinal MH - Reactive Oxygen Species/metabolism MH - *Thymelaeaceae/chemistry MH - Time Factors OTO - NOTNLM OT - Apoptosis OT - Aquilariae Lignum OT - Calcium overload OT - Calpain-dependent OT - Excitotoxicity EDAT- 2018/08/19 06:00 MHDA- 2018/11/27 06:00 CRDT- 2018/08/19 06:00 PHST- 2018/04/02 00:00 [received] PHST- 2018/07/05 00:00 [revised] PHST- 2018/07/06 00:00 [accepted] PHST- 2018/08/19 06:00 [pubmed] PHST- 2018/11/27 06:00 [medline] PHST- 2018/08/19 06:00 [entrez] AID - S0753-3322(18)32203-0 [pii] AID - 10.1016/j.biopha.2018.07.032 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Oct;106:1031-1038. doi: 10.1016/j.biopha.2018.07.032. Epub 2018 Jul 17.