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BMC Complement Altern Med ; 13: 161, 2013 Jul 06.
Article in English | MEDLINE | ID: mdl-23829668

ABSTRACT

BACKGROUND: To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats' hippocampus. METHODS: A rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats' hippocampus. RESULTS: Compared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats' hippocampus. CONCLUSIONS: Treatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats' hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats' hippocampus and as a result improved the cognitive function.


Subject(s)
Cognition Disorders/drug therapy , Cognition/drug effects , Diabetes Mellitus, Type 2/psychology , Drugs, Chinese Herbal/therapeutic use , Hippocampus/drug effects , Insulin Resistance , Phytotherapy , Animals , Camellia sinensis , Cognition Disorders/etiology , Cognition Disorders/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/psychology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Endoplasmic Reticulum Stress/drug effects , Glucose Tolerance Test , Hippocampus/metabolism , Insulin/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Male , Panax , Phosphorylation , Polygala , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects
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