Aim: Ginseng, a traditional herbal medicine, has been shown to prevent the progression of dementia, but its therapeutic effects vary because ginseng's components must first be activated by intestinal bacteria before being absorbed into the blood. We therefore focused on a fermented ginseng (FG), which contains activated components prepared by Lactobacillus paracasei A221, and compared its effects with those of non-FG. In this study, we investigated whether FG is effective on spatial memory impairment in rats. Methods: Rats with spatial memory impairment were prepared with transient cerebral ischemia and intraventricular injection of β-amyloid 1-42 for 7 days (CI + Aβ). Oral FG or non-FG was given for 7 days after the cerebral ischemia. Spatial memory was evaluated using the Morris water maze (MWM). We observed neuronal neuclei-positive cells to assess hippocampal neuron loss, and investigated the protein expression of caspase-3 and cleaved caspase-3 for neuronal apoptosis, ionized calciumbinding adapter molecule 1 (Iba-1) for microglia, and glial fibrillary acidic protein for astrocytes. Results: FG treatment in the CI + Aβ-operated rats shortened the extended time to reach the platform in the MWM, whereas non-FG treatment did not affect the extended time. FG ameliorated loss of hippocampal cornu amonis (CA)1 neurons and the increase in caspase-3 and Iba-1 in the CI + Aβ-operated rats. Conclusion: FG improved spatial memory impairment in CI + Aβ-operated rats. The effect of FG might be attributed to the amelioration of apoptotic neuronal cell death and the inactivation of microglia. FG is a more useful treatment for patients with cognitive dysfunction than non-FG.

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Phorbol myristate acetate (PMA)-induced superoxide radical (O(2)(-))-production in guinea pig peritoneal polymorphonuclear leukocytes (PMNs) was significantly lower than that in peripheral cells. To determine the role of phosphotyrosine proteins in the lower O(2)(-) production, the effect of ST638 and genistein, tyrosine kinase inhibitors, on PMA-induced O(2)(-) production in peritoneal PMNs was examined. PMA-induced O(2)(-)-production of the cells was increased by the pretreatment with ST638 or genistein, the increment depending on the inhibitor concentration. The p47phox level in the plasma membrane of PMA-stimulated PMNs was increased by the pretreatment with ST638, although the phosphorylated p47phox level in the cells was not altered by ST638. On the other hand, PMA-induced O(2)(-)-production of peripheral PMNs was not affected by the pretreatment with ST638, but that of cytochalasin B (CB)-primed peripheral PMNs significantly increased by further treatment with ST638. The phosphotyrosine protein level of peritoneal PMNs was higher than that of the peripheral cells, especially in cytosolic proteins including 50-60 and 70-85 kDa proteins, and that of the CB-primed peripheral cells was also higher than that of the intact cells in similar cytosolic proteins to those above. Further treatment of CB-primed peripheral cells with ST638 resulted in a lower level of phosphotyrosine proteins. These findings suggest that phosphorylation of some protein(s) at specific tyrosine residues inhibits the translocation of p47phox to the plasma membrane from the cytosol, resulting in lower O(2)(-)-generation in casein-induced peritoneal exudate PMNs.