title: Neuroprotection, learning and memory improvement of a standardized extract from Renshen Shouwu against neuronal injury and vascular dementia in rats with brain ischemia.
abstract: BACKGROUND
  The Renshen Shouwu capsule (RSSW) is a patented Traditional Chinese Medicine (TCM), that has been proven to improve memory and is widely used in China to apoplexy syndrome and memory deficits. To investigate the neuroprotective and therapeutic effect of the Renshen Shouwu standardized extract (RSSW) on ischemic brain neuronal injury and impairment of learning and memory related to Vascular Dementia (VD) induced by a focal and global cerebral ischemia-reperfusion injury in rats.
  
  
  METHODS
  Using in vivo rat models of both focal ischemia/reperfusion (I/R) injuries induced by a middle cerebral artery occlusion (MCAO), and VD with transient global brain I/R neuronal injuries induced by a four-vessel occlusion (4-VO) in Sprague-Dawley (SD) rats, RSSW (50,100, and 200 mg kg(-1) body weights) and Egb761® (80 mg kg(-1)) were administered orally for 20 days (preventively 6 days+therapeutically 14 days) in 4-VO rats, and for 7 days (3 days preventively+4 days therapeutically) in MCAO rats. Learning and memory behavioral performance was assayed using a Morris water maze test including a place navigation trial and a spatial probe trial. Brain histochemical morphology and hippocampal neuron survival was quantified using microscope assay of a puffin brain/hippocampus slice with cresyl violet staining.
  
  
  RESULTS
  MCAO ischemia/reperfusion caused infarct damage in rat brain tissue. 4-VO ischemia/reperfusion caused a hippocampal neuronal lesion and learning and memory deficits in rats. Administration of RSSW (50, 100, and 200mg/kg) or EGb761 significantly reduced the size of the insulted brain hemisphere lesion and improved the neurological behavior of MCAO rats. In addition, RSSW markedly reduced an increase in the brain infarct volume from an I/R-induced MCAO and reduced the cerebral water content in a dose-dependent way. Administration of RSSW also increased the pyramidal neuronal density in the hippocampus of surviving rats after transient global brain ischemia and improved the learning and memory ability of rats with 4-VO induced vascular dementia in a dose-dependent manner.
  
  
  CONCLUSIONS
  The in vivo results suggested that RSSW has significant neuroprotective effects against MCAO and 4-VO I/R injury and a therapeutic effect on cognitive disorders in VD rats. RSSW also improved the learning and memory ability of VD rats. These results convincingly demonstrated that RSSW may be useful to prevent and treat ischemia/reperfusion injury and vascular dementia disease.
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of neuropharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Zhanyuan
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of neuropharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Haibiao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Quanlin
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of neuropharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: jpx@smu.edu.cn.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Xu
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China. Electronic address: 806362747@139.com.
authors.forename: Weijian
authors.initials: W
authors.lastname: Bei
authors.affiliation: Guangdong TCM key laboratory against metabolic diseases, Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), SATCM Level 3 Lab of Lipid Metabolism, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D015140:Dementia, Vascular / Q000517:prevention & control*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018697:Nootropic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005894:Panax / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D018697:Nootropic Agents
keywords: Four-vessel occlusion; Ischemia/reperfusion injury; Middle cerebral artery occlusion; Neuroprotection; Renshen Shouwu; Vascular dementia