title: Saponins from Panax japonicus attenuate D-galactose-induced cognitive impairment through its anti-oxidative and anti-apoptotic effects in rats.
abstract: OBJECTIVE
  To investigate the neuroprotective effects of saponins from Panax japonicus (SPJ) on D-galactose (D-gal)-induced brain ageing, and further explore the underlying mechanisms.
  
  
  METHODS
  SPJ were analysed using high-pressure liquid chromatography. Male Wistar rats weighing 200 ± 20 g were randomly divided into four groups: control group (saline), D-gal-treated group (400 mg/kg, subcutaneously), D-gal + SPJ groups (50, 100 and 200 mg/kg, orally) and vitamin E group (100 mg/kg). Rats were injected corresponding drugs once daily for 8 weeks. Neuroprotective effects of SPJ were evaluated by Morris water maze, histopathological observations, biochemical assays, western blot analysis and quantitative real-time polymerase chain reaction (PCR) analysis in vivo as well as reactive oxygen species (ROS) measurement and apoptosis assay in vitro.
  
  
  RESULTS
  Our present study showed that D-gal had a neurotoxic effect in rats and in SH-SY5Y cells due to oxidative stress induction, including decreased total anti-oxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase activity, ultimately leading to spatial learning and memory impairment in rats and ROS accumulation in SH-SY5Y cells. SPJ improved spatial learning and memory deficits, attenuated hippocampus histopathological injury and restored impaired anti-oxidative as well as anti-apoptotic capacities in D-gal-induced ageing rats. In addition, SPJ remarkably decreased lipofuscin levels, increased hippocampus nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homologue (SIRT1) protein levels and anti-oxidant genes expression such as manganese superoxide dismutase (Mn-SOD), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1) and cysteine ligase catalytic (GCLC) in D-gal-induced brain ageing.
  
  
  CONCLUSIONS
  Our data suggested that D-gal induced multiple molecular and functional changes in brain similar to natural ageing process. SPJ protected brain from D-gal-induced neuronal injury through decreasing oxidative stress and apoptosis, and ultimately improving cognitive performance in D-gal-induced brain ageing. It is possibly related to Nrf2 and SIRT1-mediated anti-oxidant signalling pathways.
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Guojie
authors.initials: G
authors.lastname: Di
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Yaoyan
authors.initials: Y
authors.lastname: Dun
authors.affiliation: Three Gorges Career Technical College of Nursing.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Wan
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Ben
authors.initials: B
authors.lastname: Peng
authors.affiliation: Institute of Molecular Biology, Three Gorges University.
authors.forename: Chaoqi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Second People's Hospital of China, Three Gorges University.
authors.forename: Guangrun
authors.initials: G
authors.lastname: Xiong
authors.affiliation: College of Medical Science, Three Gorges University.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Medical Science, Three Gorges University.|Renhe Hospital, Three Gorges University.
authors.forename: Ding
authors.initials: D
authors.lastname: Yuan
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005690:Galactose / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008062:Lipofuscin / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D005894:Panax / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008062:Lipofuscin; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012503:Saponins; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D005690:Galactose
keywords: apoptosis; braining ageing; oxidative stress; saponins from Panax japonicus