PMID- 29895492 OWN - NLM STAT- MEDLINE DCOM- 20180702 LR - 20220408 IS - 1618-095X (Electronic) IS - 0944-7113 (Linking) VI - 44 DP - 2018 May 15 TI - Anti-neuroinflammatory effects of Ginkgo biloba extract EGb761 in LPS-activated primary microglial cells. PG - 45-55 LID - S0944-7113(18)30109-0 [pii] LID - 10.1016/j.phymed.2018.04.009 [doi] AB - BACKGROUND: Neuroinflammation is a key factor of Alzheimer's disease (AD) and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system (CNS). They play an essential role in the maintenance of homeostasis and responses to neuroinflammation. Ginkgo biloba extract EGb 761 is one of the most commonly used natural medicines owing to its established efficacy and remarkable biological activities especially in respect to CNS diseases. However, only few studies have addressed the effects and mechanisms of Ginkgo biloba extract in microglia activation. METHODS: We measured the production of pro-inflammatory mediators and cytokines by ELISA and analyzed gene expressions by qRT-PCR and Western Blot in LPS treated cultured primary rat microglia. RESULTS: The Ginkgo biloba extract EGb 761 significantly inhibited the release of prostaglandin E(2) (PGE(2)) and differentially regulated the levels of pro-inflammatory cytokines. The inhibition of LPS-induced PGE(2) release in primary microglia was partially dependent on reduced protein synthesis of mPGES-1 and the reduction in the activation of cytosolic phospholipase A2 (cPLA2) without altering COX-2 enzymatic activity, inhibitor of kappa B alpha (IkappaBalpha) degradation, and the activation of multiple mitogen activated protein kinases (MAPKs). Altogether, we showed that EGb 761 reduces neuro-inflammatory activation in primary microglial cells by targeting PGE(2) release and cytokines. CONCLUSION: Ginkgo biloba extract EGb 761 displayed anti-neuroinflammatory activity in LPS-activated primary microglia cells. EGb 761 was able to reduce neuroinflammatory activation by targeting the COX/PGE(2) pathway. This effect might contribute to the established clinical cognitive efficacy in Alzheimer's disease, vascular and mixed dementia. CI - Copyright (c) 2018 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Gargouri, Brahim AU - Gargouri B AD - Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany. FAU - Carstensen, Johanna AU - Carstensen J AD - Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany. FAU - Bhatia, Harsharan S AU - Bhatia HS AD - Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany. FAU - Huell, Michael AU - Huell M AD - Zentrum fur Psychiatrie Emmendingen, Neubronnstr. 25, 79312 Emmendingen, Germany. FAU - Dietz, Gunnar P H AU - Dietz GPH AD - Dr. Willmar Schwabe GmbH & Co. KG, Bunsenstr. 6-10, 76275 Ettlingen, Germany. FAU - Fiebich, Bernd L AU - Fiebich BL AD - Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany. Electronic address: bernd.fiebich@uniklinik-freiburg.de. LA - eng PT - Journal Article DEP - 20180406 PL - Germany TA - Phytomedicine JT - Phytomedicine : international journal of phytotherapy and phytopharmacology JID - 9438794 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cytokines) RN - 0 (I-kappa B Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Plant Extracts) RN - 19FUJ2C58T (Ginkgo biloba extract) RN - 27415-26-5 (8-epi-prostaglandin F2alpha) RN - B7IN85G1HY (Dinoprost) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.1.4 (Group IV Phospholipases A2) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Cells, Cultured MH - Cyclooxygenase 2/metabolism MH - Cytokines/metabolism MH - Dinoprost/analogs & derivatives/metabolism MH - Dinoprostone/metabolism MH - Ginkgo biloba MH - Group IV Phospholipases A2/metabolism MH - I-kappa B Proteins/antagonists & inhibitors/metabolism MH - Lipopolysaccharides/pharmacology MH - Microglia/*drug effects/metabolism/pathology MH - Mitogen-Activated Protein Kinases/metabolism MH - Plant Extracts/*pharmacology MH - Rats OTO - NOTNLM OT - Alzheimer's disease OT - Cyclooxygenase OT - Cytokines OT - Neurodegeneration OT - Neuroinflammation OT - Prostaglandin E(2) EDAT- 2018/06/14 06:00 MHDA- 2018/07/03 06:00 CRDT- 2018/06/14 06:00 PHST- 2017/12/11 00:00 [received] PHST- 2018/02/15 00:00 [revised] PHST- 2018/04/04 00:00 [accepted] PHST- 2018/06/14 06:00 [entrez] PHST- 2018/06/14 06:00 [pubmed] PHST- 2018/07/03 06:00 [medline] AID - S0944-7113(18)30109-0 [pii] AID - 10.1016/j.phymed.2018.04.009 [doi] PST - ppublish SO - Phytomedicine. 2018 May 15;44:45-55. doi: 10.1016/j.phymed.2018.04.009. Epub 2018 Apr 6.