Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling.

The flower bud of Zingiber mioga Roscoe, known as 'myoga' or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal-regulated kinases and cAMP response element-binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability.

Ginger fermented with Schizosaccharomyces pombe alleviates memory impairment via protecting hippocampal neuronal cells in amyloid beta1-42 plaque injected mice.

Ginger, which has been widely used for dietary condiment, has been reported to improve memory dysfunction in an animal model of Alzheimer's disease (AD). Recently, a few trials have been carried out to enhance the effects of ginger by improving the bioavailability of its relevant components via fermentation. Some reports have suggested that the fermented ginger has the ability to affect the AD in vitro systems; however, its anti-amnesic effects on an in vivo model still remain to be investigated. In the present study, we aimed to investigate the neuroprotective effects of ginger fermented with Schizosaccharomyces pombe (FG) in the in vivo models of AD. The neuroprotective effects were investigated by employing behavioral, western blotting, and immunohistochemical assays. The administration of FG improved recognition memory, impaired by scopolamine injection, than that of non-fermented ginger. In addition, FG ameliorated memory impairment in amyloid beta1-42 (Aß1-42) plaque-injected mice via protecting neuronal cells in the CA3 area of the mouse hippocampus. Moreover, FG reinstated the pre- and postsynaptic protein levels decreased by Aß1-42 plaque-toxicity. Overall, these data suggest that FG attenuates memory impairment in Aß1-42 plaque-induced AD mice through inhibition of neuronal cell loss and synaptic disruption.

An Optimized Combination of Ginger and Peony Root Effectively Inhibits Amyloid-ß Accumulation and Amyloid-ß-Mediated Pathology in AßPP/PS1 Double-Transgenic Mice.

The progressive aggregation of amyloid-ß protein (Aß) into senile plaques is a major pathological factor of Alzheimer's disease (AD) and is believed to result in memory impairment. We aimed to investigate the effect of an optimized combination of ginger and peony root (OCGP), a standardized herbal mixture of ginger and peony root, on Aß accumulation and memory impairment in amyloid-ß protein precursor (AßPP)/presenilin 1 (PS1) double-transgenic mice. In an in vitro thioflavin T fluorescence assay, 100 µg/ml OCGP inhibited Aß accumulation to the same extent as did 10 µM curcumin. Furthermore, AßPP/PS1 double-transgenic mice treated with OCGP (50 or 100 mg/kg/day given orally for 14 weeks) exhibited reduced Aß plaque accumulation in the hippocampus and lower levels of glial fibrillary acid protein and cyclooxygease-2 expression compared with vehicle-treated controls. These results suggest that OCGP may prevent memory impairment in AD by inhibiting Aß accumulation and inflammation in the brain.

Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3ß pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: A growing body of literature supports the concept that antiaging herbs may be potential candidates for use in treating age-related neurodegeneration, including Alzheimer׳s disease (AD). Mori Fructus is a well-known traditional herbal medicine, food, and dietary supplement. This study employed models of amyloid beta (Aß)-induced AD to investigate the protective effects of Mori Fructus ethanol extract (ME) against age-related disease and cognitive deficits. MATERIALS AND METHODS: To examine the protective effect of ME, we measured cell viability, cytotoxicity, and survival in rat primary hippocampal cultures. We performed behavioral tests and histological analysis in mouse models of AD induced by Aß(25-35) toxicity. To investigate the mechanism underlying the protective effect, we performed western blotting using antibodies against apoptotic markers as well as the nonphosphorylated and phosphorylated forms of Akt, glycogen synthase kinase-3ß (GSK-3ß), and tau. We also measured apoptotic marker fluorescence intensity. RESULTS: ME significantly attenuated Aß-induced cell damage, enhanced Akt and GSK-3ß phosphorylation, and reduced tau phosphorylation. ME reduced apoptotic markers that were activated by GSK-3ß, and reduced reactive oxygen species production. Further, ME decreased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X expression ratio, mitochondria depolarization, cytochrome c release from mitochondria, and caspase-3 activation. We confirmed that ME treatment improved cognitive impairment and neuronal cell death induced by Aß(25-35) toxicity in the mouse hippocampus via its antiapoptotic activity. CONCLUSIONS: These results indicate that ME protects cognition and neurons in AD-like models induced by Aß via reduction of tau phosphorylation and apoptosis through GSK-3ß inactivation.

Coriander alleviates 2,4-dinitrochlorobenzene-induced contact dermatitis-like skin lesions in mice.

Contact dermatitis (CD) is a pattern of inflammatory responses in the skin that occurs through contact with external factors. The clinical picture is a polymorphic pattern of skin inflammation characterized by a wide range of clinical features, including itching, redness, scaling, and erythema. Coriandrum sativum L. (CS), commonly known as coriander, is a member of the Apiaceae family and is cultivated throughout the world for its nutritional and culinary values. Linoleic acid and linolenic acid in CS have various pharmacological activities. However, no study of the inhibitory effects of CS on CD has been reported. In this study, we demonstrated the protective effect of CS against 2,4-dinitrochlorobenzene-induced CD-like skin lesions. CS, at doses of 0.5-1%, applied to the dorsal skin inhibited the development of CD-like skin lesions. Moreover, the Th2-mediated inflammatory cytokines, immunoglobulin E, tumor necrosis factor-α, interferon-γ, interleukin (IL)-1, IL-4, and IL-13, were significantly reduced. In addition, CS increased the levels of total glutathione and heme oxygenase-1 protein. Thus, CS can inhibit the development of CD-like skin lesions in mice by regulating immune mediators and may be an effective alternative therapy for contact diseases.

Ginger improves cognitive function via NGF-induced ERK/CREB activation in the hippocampus of the mouse.

Ginger (the rhizome of Zingiber officinale Roscoe) has been used worldwide for many centuries in cooking and for treatment of several diseases. The main pharmacological properties of ginger include anti-inflammatory, antihyperglycemic, antiarthritic, antiemetic and neuroprotective actions. Recent studies demonstrated that ginger significantly enhances cognitive function in various cognitive disorders as well as in healthy brain. However, the biochemical mechanisms underlying the ginger-mediated enhancement of cognition have not yet been studied in normal or diseased brain. In the present study, we assessed the memory-enhancing effects of dried ginger extract (GE) in a model of scopolamine-induced memory deficits and in normal animals by performing a novel object recognition test. We found that GE administration significantly improved the ability of mice to recognize novel objects, indicating improvements in learning and memory. Furthermore, to elucidate the mechanisms of GE-mediated cognitive enhancement, we focused on nerve growth factor (NGF)-induced signaling pathways. NGF enzyme-linked immunosorbent assay analysis revealed that GE administration led to elevated NGF levels in both the mouse hippocampus and rat glioma C6 cells. GE administration also resulted in phosphorylation of extracellular-signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB), as revealed by Western blotting analysis. Neutralization of NGF with a specific NGF antibody inhibited GE-triggered activation of ERK and CREB in the hippocampus. Also, GE treatment significantly increased pre- and postsynaptic markers, synaptophysin and PSD-95, which are related to synapse formation in the brain. These data suggest that GE has a synaptogenic effect via NGF-induced ERK/CREB activation, resulting in memory enhancement.