title: Diammonium glycyrrhizinate upregulates PGC-1α and protects against Aβ1-42-induced neurotoxicity.
abstract: Mitochondrial dysfunction is a hallmark of beta-amyloid (Aβ)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection. In the present study, the neuroprotective effects of DG on Aβ(1-42)-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aβ(1-42) resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aβ(1-42) exposure. All these effects induced by Aβ(1-42) were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aβ(1-42)-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aβ(1-42)-induced AD mice in the Morris water maze test. Therefore, these results demonstrated that DG could attenuate Aβ(1-42)-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aβ(1-42)-induced AD mice, indicating that DG exerted potential beneficial effects on AD.
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Ye
authors.forename: Dening
authors.initials: D
authors.lastname: Guan
authors.forename: Lan
authors.initials: L
authors.lastname: Ye
authors.forename: Jiali
authors.initials: J
authors.lastname: Jin
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Yanting
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D014157:Transcription Factors; C075222:amyloid beta-protein (1-42); D019695:Glycyrrhizic Acid; D053148:Caspase 3; D053453:Caspase 9