title: Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat.
abstract: BACKGROUND
  Liuwei Dihuang decoction (LWDHD) is a well-known prescription of traditional Chinese medicine (TCM) and consists of six crude drugs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea oppositifolia L. (family: Dioscoreaceae), Paoenia ostii (family: Paeoniaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae) and Poria cocos (Schw.) Wolf (family: Polyporaceae). It has been used for the treatment of "Kidney-Yin" deficiency syndrome in clinic in China for a long time. Recent studies found that LWDHD had a potential benefit for the treatment of diabetic complications. The aim of the present study is to investigate the neuroprotective effect of LWDHD on memory and cognition deficits in streptozotocin (STZ)-induced diabetic encephalopathy (DE) rats.
  
  
  METHODS
  Adult male Sprague Dawley (SD) rats were fed with high-glucose-fat diet for 50 days and then received an intraperitoneal injection of STZ (40 mg/kg) to induce DE model. Morris water maze test was used to evaluate the memory and cognition capability of DE rats. Choline acetyltransferase (ChAT), acetylcholinesterase (AChE), Na(+)-K(+)-ATP enzyme, iNOS and GSH kits were used to determine their activities or content in hippocampus. TUNEL staining, immunohistochemistry and Congo red staining were conducted to evaluate the apoptosis, caspase-3 protein expression, insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) expressions, as well as Aβ deposition.
  
  
  RESULTS
  The treatment with LWDHD (1 and 2g/kg, p.o., once daily, 30 days) could significantly reduce the escape latency time and path length, and obviously enhance the spent time in the target quadrant and platform crossings in Morris water maze test compared with model group (P<0.05, P<0.01). LWDHD could also significantly decrease the level of fasting blood glucose, increase Na(+)-K(+)-ATP enzyme and ChAT activities, enhance remarkedly GSH level while decrease significantly AChE and iNOS activities in hippocampus (P<0.05, P<0.01). Furthermore, TUNEL staining, Congo red staining and immunohistochemistry showed that LWDHD significantly improved the expressions of IGF-1 and BDNF, attenuated the neural apoptosis, overexpression of caspase-3 and Aβ deposition in the hippocampus and cerebral cortex of STZ-induced DE rats (P<0.01).
  
  
  CONCLUSIONS
  Our findings suggested that LWDHD had a neuroprotective effect on DE rats. LWDHD may be of benefit in the treatment of DE.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Jiangsu, Nanjing 210009, PR China; Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang 712046, PR China.
authors.forename: Ji-ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Ming-hua
authors.initials: MH
authors.lastname: Zhang
authors.forename: Dong-ying
authors.initials: DY
authors.lastname: Ma
authors.forename: Shu-yuan
authors.initials: SY
authors.lastname: Wang
authors.forename: Junfei
authors.initials: J
authors.lastname: Gu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Rong
authors.initials: R
authors.lastname: Qu
authors.forename: Shi-ping
authors.initials: SP
authors.lastname: Ma
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; C042579:Liuwei Dihuang Decoction; D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione
keywords: AChE; AD; ANOVA; Alzheimer's disease; Anti-apoptosis; Aβ; BDNF; ChAT; Cognition deficits; DAB; DE; DM; Diabetic encephalopathy; GSH; IGF-1; LWDHD; Liuwei Dihuang decoction; NO; Na(+)–K(+)-ATPase; Na(+)–K(+)-adenosine triphosphatase; Neuropathological changes; OGD; Oxidative stress; ROS; SD; STZ; Sprague Dawley; TCM; TUNEL; acetylcholinesterase; amyloid beta; brain derived neurophic factor; choline acetyltransferase; diabetes mellitus; diabetic encephalopathy; diaminobenzidine; glutathione; insulin-like growth factors 1; nitric oxide; one-way analysis of variance.; oxygen–glucose deprivation; reactive oxygen species; streptozotocin; terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay; traditional Chinese medicine