Geniposide Protects Primary Cortical Neurons against Oligomeric Aβ1-42-Induced Neurotoxicity through a Mitochondrial Pathway

• Published in: PloS one 2016-04, Vol.11 (4), p.e0152551
• Main Authors: Zhao, Chunhui, Lv, Cui, Li, Hang, Du, Shijing, Liu, Xiaoli, Li, Zhi, Xin, Wenfeng, Zhang, Wensheng
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Alzheimers disease; Amyloid beta-Peptides - metabolism; Animal models; Animals; Apoptosis; Apoptosis - drug effects; Biology and Life Sciences; Biopolymers - chemistry; Biopolymers - pharmacology; Biotechnology; Blood-brain barrier; Brain research; Caspase; Caspase-3; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Chinese medicine; Cytochrome; Cytochrome-c oxidase; Education; Engineering research; Female; Iridoids - pharmacology; Laboratories; Male; Medicine and Health Sciences; Membrane potential; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Nervous system; Neurodegenerative diseases; Neurons; Neurons - drug effects; Neurosciences; Neurotoxicity; Oxidative stress; Peptide Fragments - metabolism; Pharmaceuticals; Pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; Science; Transgenic mice; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152551

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.