PMID- 27046221 OWN - NLM STAT- MEDLINE DCOM- 20160815 LR - 20190219 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 4 DP - 2016 TI - Geniposide Protects Primary Cortical Neurons against Oligomeric Abeta1-42-Induced Neurotoxicity through a Mitochondrial Pathway. PG - e0152551 LID - 10.1371/journal.pone.0152551 [doi] LID - e0152551 AB - Mitochondrial dysfunction plays a key role in the progression of Alzheimer's disease (AD). The accumulation of amyloid-beta peptide (Abeta) in the brains of AD patients is thought to be closely related to neuronal mitochondrial dysfunction and oxidative stress. Therefore, protecting mitochondria from Abeta-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 Abeta-induced neuronal dysfunction remains unknown. In the present study, we demonstrate that geniposide protects cultured primary cortical neurons from Abeta-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 Abeta-induced neuronal injury by inhibiting mitochondrial dysfunction and oxidative stress. FAU - Zhao, Chunhui AU - Zhao C AD - Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China. AD - College of Resources Science Technology, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. FAU - Lv, Cui AU - Lv C AD - Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China. AD - Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Shandong Academy of science, Jinan, China. AD - College of Resources Science Technology, Beijing Normal University, Beijing, China. FAU - Li, Hang AU - Li H AD - Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China. AD - College of Resources Science Technology, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. FAU - Du, Shijing AU - Du S AD - Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China. AD - College of Resources Science Technology, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. FAU - Liu, Xiaoli AU - Liu X AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming, China. FAU - Li, Zhi AU - Li Z AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. FAU - Xin, Wenfeng AU - Xin W AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming, China. FAU - Zhang, Wensheng AU - Zhang W AD - Beijing Area Major Laboratory of Protection and Utilization of Traditional Chinese Medicine, Beijing Normal University, Beijing, China. AD - College of Resources Science Technology, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, China. AD - Engineering Research Center of Sanqi Biotechnology and Pharmaceutical, Yun Nan Province, Kunming, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160405 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Amyloid beta-Peptides) RN - 0 (Biopolymers) RN - 0 (Iridoids) RN - 0 (Peptide Fragments) RN - 0 (Reactive Oxygen Species) RN - 0 (amyloid beta-protein (1-42)) RN - 145295QLXY (geniposide) SB - IM MH - Amyloid beta-Peptides/*metabolism MH - Animals MH - Apoptosis/drug effects MH - Biopolymers/chemistry/*pharmacology MH - Cerebral Cortex/cytology/*drug effects MH - Female MH - Iridoids/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Mitochondria/*metabolism MH - Neurons/*drug effects MH - Peptide Fragments/*metabolism MH - Reactive Oxygen Species/metabolism PMC - PMC4821580 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/04/06 06:00 MHDA- 2016/08/16 06:00 PMCR- 2016/04/05 CRDT- 2016/04/06 06:00 PHST- 2015/11/14 00:00 [received] PHST- 2016/03/16 00:00 [accepted] PHST- 2016/04/06 06:00 [entrez] PHST- 2016/04/06 06:00 [pubmed] PHST- 2016/08/16 06:00 [medline] PHST- 2016/04/05 00:00 [pmc-release] AID - PONE-D-15-48943 [pii] AID - 10.1371/journal.pone.0152551 [doi] PST - epublish SO - PLoS One. 2016 Apr 5;11(4):e0152551. doi: 10.1371/journal.pone.0152551. eCollection 2016.