Journal Article

Oxymatrine attenuates diabetes-associated cognitive deficits in rats

Suo-bin WANG Jian-ping JIA

2014

Overview

Aim： Oxymatrine （OMT） is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait （the Chinese herb Kushen） and exhibits diverse pharmacological actions. In this work we investigated the effects of OMT on diabetes-associated cognitive decline （DACD） in a rat model of diabetes and explored the mechanisms of action. Methods： Male Wistar rats were injected with streptozotocin （65 mg/kg, ip） once to induce diabetes. The rats were then treated with vehicle or OMT （60 or 120 mg/kgper day, ip） for 7 weeks. Memory function was assessed using Morris water maze test. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD）, glutathione （GSH）, NF-KB p65 unit, TNF-a, IL-113 and caspase-3 in the cerebral cortex and hippocampus were quantified. Results： The diabetic rats exhibited markedly reduced body weight and increased plasma glucose level. The memory function of the rats assessed using Morris water maze test showed significant reduction in the percentage of time spent in the target quadrant and the number of times crossing the platform, coupled with markedly prolongation of escape latency and mean path length. Moreover, the rats showed oxidative stress （significantly increased MDA, decreased SOD and reduced GSH levels）, as well as significant increases of NF-KB p65 unit, TNF-（x, IL-113 and caspase-3 lew.~ls in the cerebral cortex and hippocampus. Chronic treatment with OMT dose- dependently reversed these behavioral, biochemical and molecular changes in the diabetic rats. However, the swimming speed had no significant difference among the control, diabetic and OMT-treated diabetic rats. Conclusion： Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Alkaloids - pharmacology / Animals / Anti-Inflammatory Agents - pharmacology / Antioxidants - pharmacology / Behavior, Animal - drug effects / Biomedical and Life Sciences / Biomedicine / Blood Glucose - drug effects / Blood Glucose - metabolism / Body Weight - drug effects / Caspase 3 - metabolism / caspase-3 / Cerebral Cortex - drug effects / Cerebral Cortex - metabolism / Cerebral Cortex - physiopathology / Cognition - drug effects / Cognition Disorders - blood / Cognition Disorders - chemically induced / Cognition Disorders - physiopathology / Cognition Disorders - prevention & control / Cognition Disorders - psychology / Diabetes Mellitus, Experimental - blood / Diabetes Mellitus, Experimental - chemically induced / Diabetes Mellitus, Experimental - drug therapy / Diabetes Mellitus, Experimental - physiopathology / Diabetes Mellitus, Experimental - psychology / Dose-Response Relationship, Drug / Glutathione - metabolism / Hippocampus - drug effects / Hippocampus - metabolism / Hippocampus - physiopathology / Immunology / Inflammation Mediators - metabolism / Interleukin-1beta - metabolism / Internal Medicine / Male / Malondialdehyde - metabolism / Maze Learning - drug effects / Medical Microbiology / Memory - drug effects / Morris水迷宫 / Motor Activity - drug effects / Original / original-article / Oxidative Stress - drug effects / Pharmacology/Toxicology / Quinolizines - pharmacology / Rats, Wistar / Sophora / Streptozocin / Superoxide Dismutase - metabolism / Time Factors / Transcription Factor RelA - metabolism / Tumor Necrosis Factor-alpha - metabolism / Vaccine / Wistar大鼠 / 大鼠模型 / 氧化苦参碱 / 糖尿病大鼠 / 认知障碍 / 超氧化物歧化酶