Increasing evidence suggests that neurodegenerative disorders such as Alzheimer's disease (AD) are mediated via disruption of cholinergic neurons and enhanced oxidative stress. Therefore, attention has been focused on searching for antioxidant phytochemicals for the prevention and/or treatment of AD through their ability to fortify cholinergic function and antioxidant defense capacity. In this study, we have investigated the neuroprotective effect of α-pinene (APN) against learning and memory impairment induced by scopolamine (SCO, 1 mg/kg, i.p.), a muscarinic receptor antagonist in C57BL/6 mice. Administration of APN (10 mg/kg, i.p.) significantly improved SCO-induced cognitive dysfunction as assessed by Y-maze and passive avoidance tests. In Morris water-maze test, APN effectively shortened the mean escape latency to find the hidden platform during training days. To further elucidate the molecular mechanisms underlying the neuroprotective effect of APN, the expression of proteins involved in the acetylcholine metabolism and antioxidant system was examined. Particularly, APN treatment increased mRNA expression of choline acetyltransferase in the cortex and protein levels of antioxidant enzymes such as heme oxygenase-1 and manganese superoxide dismutase in the hippocampus via activation of NF-E2-related factor 2. These findings suggest the possible neuroprotective potentials of APN for the management of dementia with learning and memory loss.

β-amyloid peptide (Aβ), a major component of senile plaques, plays important roles in neuropathology of Alzheimer's disease (AD). An array of in vitro and in vivo data indicates that Aβ-induced neuronal death is mediated by oxidative stress. In this study, we aimed to investigate effects of sulforaphane (SUL), an isothiocyanate in cruciferous vegetables, on Aβ-induced oxidative cell death in SH-SY5Y cells. Cells treated with Aβ 25–35 exhibited decreased cell viability and underwent apoptosis as determined by MTT assay and TUNEL, respectively. Aβ 25–35-induced cytotoxicity and apoptotic characteristics such as activation of c-JNK, dissipation of mitochondrial membrane potential, altered expression of Bcl-2 family proteins, and DNA fragmentation were effectively attenuated by SUL pretreatment. The antiapoptotic activity of SUL seemed to be mediated by inhibition of intracellular accumulation of reactive oxygen species and oxidative damages. SUL exerted antioxidant potential by upregulating expression of antioxidant enzymes including γ-glutamylcysteine ligase, NAD(P)H:quinone oxidoreductase-1, and heme oxygenase-1 via activation of NF-E2-related factor 2(Nrf2). The protective effect of SUL against Aβ 25–35-induced apoptotic cell death was abolished by siRNA of Nrf2. Taken together, the results suggest that pharmacologic activation of Nrf2 signaling pathway by SUL might be a practical prevention and/or protective treatment for the management of AD.

beta-Amyloid (Abeta) peptide, a major component of senile plaques has been regarded to play a crucial role in the development and neuropathogenesis of Alzheimer's disease (AD). Increasing data from in vitro and in vivo studies indicate that Abeta-induced damages in neurons and glia are mediated via nitrosative as well as oxidative stress. Therefore, recent researches have been focused on searching for dietary and herbal manipulations to protect against the Abeta-induced oxidative and/or nitrosative cell death. Epigallocatechin-3-gallate (EGCG), one of these candidates is a major polyphenolic compound present in green tea and has been reported to exhibit potent antioxidant and anti-inflammatory properties. In the present study, we have investigated the effect of EGCG against Abeta-induced oxidative and/or nitrosative cell death in BV2 microglia. Abeta treatment led to apoptosis in BV2 cells as revealed by DNA fragmentation, perturbation of mitochondrial transmembrane potential, and alterations in the expression of apoptosis-regulator Bcl-2 family proteins. EGCG pretreatment effectively ameliorated Abeta-induced cytotoxicity and manifestation of proapoptotic signals. Furthermore, BV2 cells exposed to Abeta underwent nitrosative stress as shown by the increased expression of inducible nitric oxide synthase (iNOS) and subsequent production of nitric oxide (NO) and peroxynitrite, which were effectively suppressed by EGCG pretreatment. To elucidate a molecular mechanism underlying the neuroprotective effect of EGCG, we have examined the cellular metabolism of reduced glutathione (GSH) with antioxidant properties. EGCG treatment fortified cellular GSH pool through elevated mRNA expression of gamma-glutamylcysteine ligase (GCL), the rate limiting enzyme in the glutathione biosynthesis. These results suggest that EGCG may have preventive and/or therapeutic potential in AD patients by augmenting cellular antioxidant defense capacity and attenuating Abeta-mediated oxidative and/or nitrosative cell death.

We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day). To further verify the neuroprotective mechanism of GIN, we have focused on the brain-derived neurotrophic factor (BDNF). The administration of GIN elevated the protein expression of BDNF, which was mediated via the activation of protein kinase B/Akt- and cAMP-response element binding protein (CREB) signaling pathway. These results suggest that GIN may have preventive and/or therapeutic potentials in the management of memory deficit and cognitive impairment in mice with amnesia.

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