title: ZiBu PiYin recipe prevents diabetes-associated cognitive decline in rats: possible involvement of ameliorating mitochondrial dysfunction, insulin resistance pathway and histopathological changes.
abstract: BACKGROUND
  Disturbance in energy metabolism, as a key factor in diabetes-associated cognitive decline (DACD), has become a promising therapeutic target of Chinese medicine ZiBu PiYin Recipe (ZBPYR). However, it is still not clear how ZBPYR affects the mitochondrial function in DACD rats' brains, which is considered as the crucial cell organelle to supply energy for the brain.
  
  
  METHODS
  Type 2 diabetes mellitus (T2DM) rat models were established by using high fat diet and streptozotocin (STZ) (30 mg/kg, ip). The evaluation of insulin sensitivity was performed by oral glucose tolerance and insulin tolerance test. After 7 weeks, the T2DM rats were treated with vehicle or ZBPYR for 11 weeks and morris water maze (MWM) test were used to evaluate memory function. The ultra structural changes of prefrontal cortex (PFC) and hippocampus were examined by transmission electron microscopy (TEM). The mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) were measured with JC-1 and DCFDA assay. The levels of insulin proteins were quantified by Western Blot analysis and the markers of histopathological changes were detected by immunohistochemistry.
  
  
  RESULTS
  ZBPYR could alleviate learning and memory impairment of DACD rats. TEM showed that ZBPYR prevented mitochondrial ultra-structural alterations and number changes in the PFC and hippocampus of the DACD rats. In addition, ZBPYR significantly increased ΔΨm and lowered the levels of ROS. Further investigation indicated that ZBPYR suppressed the release of cytochrome c from mitochondria, strengthened insulin signaling and inhibited GSK3β over-expression. These positive effects were associated with reduced Aβ1-42 deposition and restored expression levels of microtubule-associated protein MAP2.
  
  
  CONCLUSIONS
  ZBPYR showed excellent protective effect against DACD via ameliorating mitochondrial dysfunction, insulin resistance and histopathological changes.
authors.affiliation: Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Nanjing University of Chinese Medicine, 138 Linxian Road, Nanjing, 210023, Jiangsu, P.R. China. zlbnj@njucm.edu.cn.|The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, Liaoning, P.R. China. zlbnj@njucm.edu.cn.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhan
authors.affiliation: Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Liang
authors.affiliation: Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.affiliation: Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Institute of Integrative Medicine, Dalian Medical University, No. 9, South Road of Lvshun, Dalian, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Sun
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, Liaoning, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
mesh_terms: D000818:Animals; D060825:Cognitive Dysfunction / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; C531140:zibu piyin
keywords: DACD; Histopathological changes; Insulin resistance; Mitochondrial dysfunction; ZBPYR