ZiBu PiYin recipe prevents diabetes-associated cognitive decline in rats: possible involvement of ameliorating mitochondrial dysfunction, insulin resistance pathway and histopathological changes.

Zheng Sun,Xiaoxin Sun,Hua Sui,Luping Zheng,Lina Liang,Wei Xie,Libin Zhan

doi:10.1186/s12906-016-1177-y

Abstract

BackgroundDisturbance 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.MethodsType 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.ResultsZBPYR 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.ConclusionZBPYR showed excellent protective effect against DACD via ameliorating mitochondrial dysfunction, insulin resistance and histopathological changes.

Highlights

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)
Effects of ZBPYR on type 2 diabetes models The results revealed that compared with the control group, the body weight, food and water intake of model rats were all increased rapidly due to the high-fat diet administered prior to the STZ injection (Fig. 2a)
The proteins which were expressed in the hippocampal groups were tested (Fig. 7b). These results indicated that compared with model groups, expression of p-Ser731 IRS2 was significantly downregulated with p < 0.05 and p-Ser473 protein kinase B (Akt) was not changed apparently by ZBPYR (p < 0.01)

Summary

Introduction

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). 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. Our recent data have demonstrated that defection in energy metabolism of hippocampus might affect the function of the brain. It might be a key determinant of DACD [7]. Preventing mitochondrial dysfunctions is taken as a new therapeutic target for DACD

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