title: Geniposide Protects Primary Cortical Neurons against Oligomeric Aβ1-42-Induced Neurotoxicity through a Mitochondrial Pathway.
abstract: Mitochondrial dysfunction plays a key role in the progression of Alzheimer's disease (AD). The accumulation of amyloid-beta peptide (Aβ) in the brains of AD patients is thought to be closely related to neuronal mitochondrial dysfunction and oxidative stress. Therefore, protecting mitochondria from Aβ-induced neurotoxicity is an effective strategy for AD therapeutics. In a previous study, we found that geniposide, a pharmacologically active compound purified from gardenia fruit, has protective effects on oxidative stress and mitochondrial dysfunction in AD transgenic mouse models. However, whether geniposide has a protective effect on Aβ-induced neuronal dysfunction remains unknown. In the present study, we demonstrate that geniposide protects cultured primary cortical neurons from Aβ-mediated mitochondrial dysfunction by recovering ATP generation, mitochondrial membrane potential (MMP), and cytochrome c oxidase (CcO) and caspase 3/9 activity; by reducing ROS production and cytochrome c leakage; as well as by inhibiting apoptosis. These findings suggest that geniposide may attenuate Aβ-induced neuronal injury by inhibiting mitochondrial dysfunction and oxidative stress.
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China.|College of Resources Science Technology, Beijing Normal University, Beijing, China.|Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China.|Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Shandong Academy of science, Jinan, China.|College of Resources Science Technology, Beijing Normal University, Beijing, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Lv
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China.|College of Resources Science Technology, Beijing Normal University, Beijing, China.|Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China.|College of Resources Science Technology, Beijing Normal University, Beijing, China.|Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Shijing
authors.initials: S
authors.lastname: Du
authors.affiliation: Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.|Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.|Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xin
authors.affiliation: Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China.|College of Resources Science Technology, Beijing Normal University, Beijing, China.|Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China.|Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001704:Biopolymers / Q000737:chemistry / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D005260:Female; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001704:Biopolymers; D039823:Iridoids; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); C007835:geniposide