Oxymatrine attenuates diabetes-associated cognitive deficits in rats.
OBJECTIVE
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.


CONCLUSIONS
Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Suo-bin
SB
Wang
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Jian-ping
JP
Jia
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011807:Quinolizines / Q000494:pharmacology*; D017208:Rats, Wistar; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D053148:Caspase 3; D005978:Glutathione; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008315:Malondialdehyde; D011807:Quinolizines; D013311:Streptozocin; D013482:Superoxide Dismutase; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C000594089:IL1B protein, rat; C498145:Rela protein, rat; C037573:oxymatrine; D000093842:Matrines; C505410:Casp3 protein, rat