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      Oxymatrine attenuates diabetes-associated cognitive deficits in rats

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          Abstract

          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/kg per 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-κB p65 unit, TNF-α, IL-1β 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-κB p65 unit, TNF-α, IL-1β and caspase-3 levels 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.

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          Most cited references33

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          Place navigation impaired in rats with hippocampal lesions.

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            Mechanisms of lipid peroxide formation in animal tissues.

            E D WILLS (1966)
            1. Homogenates of rat liver, spleen, heart and kidney form lipid peroxides when incubated in vitro and actively catalyse peroxide formation in emulsions of linoleic acid or linolenic acid. 2. In liver, catalytic activity is distributed throughout the nuclear, mitochondrial and microsomal fractions and is present in the 100000g supernatant. Activity is weak in the nuclear fraction. 3. Dilute (0.5%, w/v) homogenates catalyse peroxidation over the range pH5.0-8.0 but concentrated (5%, w/v) homogenates inhibit peroxidation and destroy peroxide if the solution is more alkaline than pH7.0. 4. Ascorbic acid increases the rate of peroxidation of unsaturated fatty acids catalysed by whole homogenates of liver, heart, kidney and spleen at pH6.0 but not at pH7.4. 5. Catalysis of peroxidation of unsaturated fatty acids by the mitochondrial and microsomal fractions of liver is inhibited by ascorbic acid at pH7.4 but the activity of the supernatant fraction is enhanced. 6. Inorganic iron or ferritin are active catalysts in the presence of ascorbic acid. 7. Lipid peroxide formation in linoleic acid or linolenic acid emulsions catalysed by tissue homogenates is partially inhibited by EDTA but stimulated by o-phenanthroline. 8. Cysteine or glutathione (1mm) inhibits peroxide formation catalysed by whole homogenates, mitochondria or haemoprotein. Inhibition increases with increase of pH.
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              Cognition and diabetes: a lifespan perspective.

              Diabetes mellitus is associated with cognitive dysfunction and abnormalities that can be seen with brain imaging. Recent studies provide important new insights into the nature and severity of these cerebral complications that help to explain why some patients with diabetes have clinically relevant neurocognitive morbidity, whereas most are apparently unaffected. This Personal View investigates the hypothesis that clinically relevant diabetes-related cognitive decrements mainly occur at two crucial periods in life: when the brain is developing in childhood, and when the brain undergoes neurodegenerative changes associated with ageing. Outside of these periods cognitive decrements mainly occur in patients with notable diabetes-related comorbidities, in particular microvascular or macrovascular complications. The identification of crucial periods and conditions for the development of diabetes-related cognitive decrements helps to draw the attention of physicians to individuals at risk and can direct future studies into the mechanisms that underlie these conditions.
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                Author and article information

                Journal
                Acta Pharmacol Sin
                Acta Pharmacol. Sin
                Acta Pharmacologica Sinica
                Nature Publishing Group
                1671-4083
                1745-7254
                March 2014
                20 January 2014
                : 35
                : 3
                : 331-338
                Affiliations
                [1 ]Department of Neurology, Xuanwu Hospital, Capital Medical University , Beijing 100053, China
                Author notes
                Article
                aps2013158
                10.1038/aps.2013.158
                4647892
                24442148
                ad8f8c79-2ec7-4638-b526-b7d79f814d08
                Copyright © 2014 CPS and SIMM
                History
                : 29 July 2013
                : 25 September 2013
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                oxymatrine,quinolizidine,diabetes,diabetes-associated cognitive decline,learning memory,oxidative stress,inflammation,apoptosis,cerebral cortex,hippocampus

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