Well-established studies have shown an elevated level of reactive oxygen species (ROS) that induces oxidative stress in the Alzheimer's disease (AD) patient's brain and an animal model of AD. Herein, we investigated the underlying anti-oxidant neuroprotective mechanism of natural dietary supplementation of anthocyanins extracted from Korean black beans in the amyloid precursor protein/presenilin-1 (APP/PS1) mouse model of AD. Both in vivo (APP/PS1 mice) and in vitro (mouse hippocampal HT22 cells) results demonstrated that anthocyanins regulate the phosphorylated-phosphatidylinositol 3-kinase-Akt-glycogen synthase kinase 3 beta (p-PI3K/Akt/GSK3β) pathways and consequently attenuate amyloid beta oligomer (AβO)-induced elevations in ROS level and oxidative stress via stimulating the master endogenous anti-oxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (Nrf2/HO-1) pathways and prevent apoptosis and neurodegeneration by suppressing the apoptotic and neurodegenerative markers such as activation of caspase-3 and PARP-1 expression as well as the TUNEL and Fluoro-Jade B-positive neuronal cells in the APP/PS1 mice. In vitro ApoTox-Glo™ Triplex assay results also showed that anthocyanins act as a potent anti-oxidant neuroprotective agent and reduce AβO-induced neurotoxicity in the HT22 cells via PI3K/Akt/Nrf2 signaling. Importantly, anthocyanins improve memory-related pre- and postsynaptic protein markers and memory functions in the APP/PS1 mice. In conclusion, our data suggested that consumption and supplementation of natural-derived anti-oxidant neuroprotective agent such as anthocyanins may be beneficial and suggest new dietary-supplement strategies for intervention in and prevention of progressive neurodegenerative diseases, such as AD.

Chronic neuroinflammation is responsible for multiple neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Lipopolysaccharide (LPS) is an essential component of the gram-negative bacterial cell wall and acts as a potent stimulator of neuroinflammation that mediates neurodegeneration. Quercetin is a natural flavonoid that is abundantly found in fruits and vegetables and has been shown to possess multiple forms of desirable biological activity including anti-inflammatory and antioxidant properties. This study aimed to evaluate the neuroprotective effect of quercetin against the detrimental effects of LPS, such as neuroinflammation-mediated neurodegeneration and synaptic/memory dysfunction, in adult mice. LPS [0.25 mg/kg/day, intraperitoneally (I.P.) injections for 1 week]-induced glial activation causes the secretion of cytokines/chemokines and other inflammatory mediators, which further activate the mitochondrial apoptotic pathway and neuronal degeneration. Compared to LPS alone, quercetin (30 mg/kg/day, I.P.) for 2 weeks (1 week prior to the LPS and 1 week cotreated with LPS) significantly reduced activated gliosis and various inflammatory markers and prevented neuroinflammation in the cortex and hippocampus of adult mice. Furthermore, quercetin rescued the mitochondrial apoptotic pathway and neuronal degeneration by regulating Bax/Bcl2, and decreasing activated cytochrome c, caspase-3 activity and cleaving PARP-1 in the cortical and hippocampal regions of the mouse brain. The quercetin treatment significantly reversed the LPS-induced synaptic loss in the cortex and hippocampus of the adult mouse brain and improved the memory performance of the LPS-treated mice. In summary, our results demonstrate that natural flavonoids such as quercetin can be beneficial against LPS-induced neurotoxicity in adult mice.

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Microglia plays a critical role in the brain and protects neuronal cells from toxins. However, over-activation of microglia leads to deleterious effects. Lipopolysaccharide (LPS) has been reported to affect neuronal cells via activation of microglia as well as directly to initiate neuroinflammation. In the present study, we evaluated the anti-inflammatory and anti-oxidative effect of anthocyanins against LPS-induced neurotoxicity in an animal model and in cell cultures. Intraperitoneal injections of LPS (250 μg/kg/day for 1 week) induce ROS production and promote neuroinflammation and neurodegeneration which ultimately leads to memory impairment. However, anthocyanins treatment at a dose of 24 mg/kg/day for 2 weeks (1 week before and 1 week co-treated with LPS) prevented ROS production, inhibited neuroinflammation and neurodegeneration, and improved memory functions in LPS-treated mice. Both histological and immunoblot analysis indicated that anthocyanins reversed the activation of JNK, prevented neuroinflammation by lowering the levels of inflammatory markers (p-NF-kB, TNF-α, and IL-1β), and reduced neuronal apoptosis by reducing the expression of Bax, cytochrome c, cleaved caspase-3, and cleaved PARP-1, while increasing the level of survival proteins p-Akt, p-GSK3β, and anti-apoptotic Bcl-2 protein. Anthocyanins treatment increased the levels of memory-related pre- and post-synaptic proteins and improved the hippocampus-dependent memory in the LPS-treated mice. Overall, this data suggested that consumption of naturally derived anti-oxidant agent such as anthocyanins ameliorated several pathological events in the LPS-treated animal model and we believe that anthocyanins would be a safe therapeutic agent for slowing the inflammation-induced neurodegeneration in the brain against several diseases such as Alzheimer's disease and Parkinson's disease.

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain. Here, we describe for the first time the development of a new, pioneering nanotechnology-based drug delivery approach for potential therapies for neurodegenerative diseases, particularly AD. We demonstrated the delivery of fluorescent carboxyl magnetic Nile Red particles (FMNPs) to the brains of normal mice using a functionalized magnetic field (FMF) composed of positive- and negative-pulsed magnetic fields generated by electromagnetic coils. The FMNPs successfully reached the brain in a few minutes and showed evidence of blood-brain barrier (BBB) crossing. Moreover, the best FMF conditions were found for inducing the FMNPs to reach the cortex and hippocampus regions. Under the same FMF conditions, dextran-coated FeO magnetic nanoparticles (MNPs) loaded with osmotin (OMNP) were transported to the brains of Aβ-treated mice. Compared with native osmotin, the OMNP potently attenuates Aβ-induced synaptic deficits, Aβ accumulation, BACE-1 expression and tau hyperphosphorylation. This magnetic drug delivery approach can be extended to preclinical and clinical use and may advance the chances of success in the treatment of neurological disorders like AD in the future.

The aim of the current study was to explore the underlying neuroprotective mechanisms of curcumin (50 mg/kg, for six weeks) against ethanol (5 mg/kg i.p., for six weeks) induced oxidative stress and inflammation-mediated cognitive dysfunction in mice. According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains. Moreover, curcumin regulated the expression of the glial cell markers in ethanol-treated mice brains, as analyzed by the relative expression TLR4 (Toll like Receptor 4), RAGE (Receptor for Advanced Glycations End products), GFAP (Glial fibrillary acidic protein), and Iba-1 (Ionized calcium binding adaptor molecule 1), through Western blot and confocal microscopic analysis. Moreover, our results showed that curcumin downregulated the expression of p-JNK (Phospo c-Jun N-Terminal Kinase), p-NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), and its downstream targets, as assessed by Western blot and confocal microscopic analysis. Finally, the expression of synaptic proteins and the behavioral results also supported the hypothesis that curcumin may inhibit memory dysfunction and behavioral alterations associated with ethanol intoxication. Altogether, to the best of our knowledge, we believe that curcumin may serve as a potential, promising, and cheaply available neuroprotective compound against ethanol-associated neurodegenerative diseases.

A field experiment was conducted during 2004-05 on wheat and rice to study the response of Zinc application in wheat-rice system. Two levels of zinc 5 and 10 kg ha(-1) with control were studied with the basal dose of N, P2O5, K2O as 120-90-60 kg ha(-1) in the form of urea, TSP, SOP and zinc sulphate during both the crops. Wheat variety Naseer 2000 and rice variety IRRI 6, both were planted in R.C.B design with three replications. Zn application, significantly affected wheat grain yield, ranged from 2.7 to 3.5 t ha(-1), giving highest increase of 31.6% over control from 5 kg Zn ha(-1). The number of tillers, spike m(-2), spike length, plant height and 1000 grain weight of wheat were also significantly affected over control with the same treatment. Paddy yield was also significantly affected by Zn levels ranged from 3.9 to 5.9 t ha(-1). The highest yield was obtained from 10 kg Zn ha(-1) each applied to both crops. Similarly Zn application also affected significantly to the yield parameters of rice like the number of spike m(-2), number of spike/plant, spike length, plant height and 1000 grain weight over control from the above said treatment of 10 kg Zn ha(-1). The concentration of zinc in soil and leaves was significantly affected by the application of zinc in wheat and rice, ranged from 0.47-1.37, 22.6-367.37 mg kg(-1) in wheat and 0.45-1.18; 29.32-40.67 mg kg(-1) in rice, respectively (soil and leaves). The highest concentration in soil and leaves was recorded by the cumulative application of 10 kg Zn ha(-1) while lowest from control. The direct application of 5 and 10 kg Zn ha(-1) gave an increase of 39 and 45% while residual effect 30.0 and 43.0%, cumulative effect of 38 and 50% over control, respectively. The residual application of 10 kg Zn ha(-1) can be recommended for economical production in wheat rice system.