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BACKGROUND: Previous Studies have demonstrated that reduced estrogen levels may accelerate the formation of advanced glycation endproducts (AGE) in brain tissue, raise the concentration of lipid peroxidation products in vivo, and speed up deterioration of learning and memory. A tonifying kidney recipe is hypothesized to improve the ability of learning and memory in ovariectomized rats by downregulating AGE and lipid peroxidation products.

OBJECTIVE: To simulate a postmenopausal state, bilateral ovariectomy (OVX) was performed in rats, and the effects of tonifying kidney recipe (TKR) on AGE and lipid peroxidation in the rat cerebral cortex, hippocampus, and blood serum levels was measured. In addition, the effects on learning and memory were evaluated, and the effect of AGE -specific inhibitor aminoguanidine (AG) was compared with TKR.

DESIGN, TIME AND SETTING: A randomized, in vivo, control experiment was performed at the scientific research center (Provincial Key Laboratory) in the Fourth Hospital of Hebei Medical University (Shijiazhuang, Hebei Province, China) from May 2005 to January 2007.

MATERIALS: Forty healthy, adult, female, Sprague Dawley rats were used for this study. TKR was composed of prepared rehmannia rhizome, epimedium herb, desert-living cistanche, and Szechwan lovage rhizome, which were provided by Shijiazhuang Medical Materials Company (China), A TKR extraction was prepared for further use. AG was provided by Sigma (USA). Forty rats were randomly divided into four groups: sham, OVX, AG. and TKR, with 10 rats in each group.

METHODS: The rat ovaries were resected in the OVX, AG and TKR groups, whereas the same volume of fat was resected in the sham group. At four weeks after OVX, the AG group received 1% AG water solution by lavage: the TKR group was administrated by lavage once per day at a dose of 6.3 g (crude drug)/kg; OVX and sham groups received equal volumes of tap water.

MAIN OUTCOME MEASURES: Learning and memory behavior of rats was tested in it Y-electric maze 16 weeks after the OVX procedure. The contents of advanced glycation endproducts in the rat cerebral cortex, hippocampus, serum. and urine were detected by competitive ELISA and spectrofluorophotometer. The contents of lipid peroxidation in rat serum, cerebral cortex, and hippocampus were assayed using a biochemical method.

RESULTS: Compared with the sham group, serum content of advanced glycation endproducts in the OVX group was significantly increased, and lipid peroxidation content increased in cerebral cortex, hippocampus, and serum (t = 3.04-4.22. P < 0.05-0.01). Both AG and TKR decreased the amount of AGE in cerebral cortex and serum (t = 2.53, 3.64, P < 0.05, 0.01), increased AGE urine content (t = 3.25-4.87, P < 0.01), and decreased lipid peroxidation content in cerebral cortex, hippocampus, and serum (t = 2.80-3.70, P < 0.05-0.01). In comparison to the OVX and sham groups, the correct escape rate in the Y-electric maze was significantly increased (t = 3.46, 3.28, P< 0.01), and escape latency was significantly decreased (t=3.12, 2.48, P < 0.05) in the AG and TKR groups, which indicated that both AG and TKR improved learning and memory. The OVX group had a significantly lower correct escape compared with the sham group (t = 4.21, P < 0.01).

CONCLUSION: The tonifying kidney recipe decreased deposition of advanced glycation endprodUCtS and lipid peroxidation in ovariectomized rats, and concomitantly improved learning and memory. The effect of TKR was equal to that of AG.