title: Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia.
abstract: We previously found that ginsenoside Rd (Rd), one of the major active ingredients in Panax ginseng, protects neuronal cells from hydrogen peroxide and oxygen-glucose deprivation, an in vitro model of cerebral ischemia. In this study, we examined the protective effects of Rd in an animal model of focal cerebral ischemia. Rats administered with Rd or vehicle were subjected to transient middle cerebral artery occlusion (MCAO). Rd (50 mg/kg) significantly reduced the infarct volume by 52.8%. This reduction of injury volume was associated with an improvement in neurological function and was sustained for at least 2 weeks after the induction of ischemia. To evaluate the underlying mechanisms of Rd against stroke, brain tissues were assayed for mitochondrial enzyme activities, mitochondrial membrane potential (MMP), production of reactive oxygen species (ROS), energy metabolites, and apoptosis. Rd markedly protected mitochondria as indicated by preserved respiratory chain complex activities and aconitase activity, lowered mitochondrial hydrogen peroxide production, and hyperpolarized MMP. Microdialysis results illustrated that Rd significantly decreased the accumulation of lactate, the end product of anaerobic glycolysis, and increased pyruvate, the end product of aerobic glycolysis, hence inducing a lower lactate/pyruvate ratio. Additionally, in vitro studies further exhibited that Rd protected isolated mitochondria from calcium-induced damage by attenuating mitochondrial swelling, preserving MMP and decreasing ROS production. Moreover, Rd treatment reduced mitochondrial release of cytochrome c (CytoC) and apoptosis-inducing factor (AIF), thereby minimizing mitochondria-mediated apoptosis following ischemia. In conclusion, these findings demonstrated that Rd exerts neuroprotective effects in transient focal ischemia, which may involve an integrated process of the mitochondrial protection, energy restoration and inhibition of apoptosis.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Ye
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Shi
authors.forename: L
authors.initials: L
authors.lastname: Xiong
authors.forename: G
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D019289:Pyruvic Acid; D000154:Aconitate Hydratase; D005947:Glucose; D002118:Calcium; C049863:ginsenoside Rd