Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood-brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl3), which mimics the sporadic form of Alzheimer's disease. Our results showed that treatment with CUR enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl3-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl3-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl3-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD.

Ginsenoside Rg1 ameliorates the cognitive deficits in D-galactose and AlCl3-induced aging mice by restoring FGF2-Akt and BDNF-TrkB signaling axis to inhibit apoptosis.

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl3. We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases.

An aluminum adjuvant-integrated nano-MOF as antigen delivery system to induce strong humoral and cellular immune responses.

Metal-organic frameworks (MOFs) have high surface area, tunable pore size, and high loading capacity, making them promising for drug delivery. However, their synthesis requires organic solvents, high temperature and high pressure that are incompatible with biomacromolecules. Zeolitic imidazole frameworks (ZIF-8) which forms through coordination between zinc ions and 2-methylimidazole (MeIM) have emerged as an advanced functional material for drug delivery due to its unique features such as high loading and pH-sensitive degradation. In this study, we took advantage of a natural biomineralization process to create aluminum-containing nanoZIF-8 particles for antigen delivery. Without organic solvents or stabilizing agent, nanoparticles (ZANPs) were synthesized by a mild and facile method with aluminum, model antigen ovalbumin (OVA) and ZIF-8 integrated. A high antigen loading capacity (%) of 30.6% and a pH dependent antigen release were achieved. A Toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides (CpG) was adsorbed on the surface of ZANPs (hereafter CpG/ZANPs) to boost the immune response. After subcutaneous injection in vivo, CpG/ZANPs targeted lymph nodes (LNs), where their cargo was efficiently internalized by LN-resident antigen-presenting cells (APCs). ZANPs decomposition in lysosomes released antigen into the cytoplasm and enhanced cross-presentation. Moreover, CpG/ZANPs induced strong antigen-specific humoral and cytotoxic T lymphocyte responses that significantly inhibited the growth of EG7-OVA tumors while showing minimal cytotoxicity. We demonstrate that ZANPs may be a safe and effective vehicle for the development of cancer vaccines.

A Polysaccharide Extract from Maitake Culinary-Medicinal Mushroom, Grifola frondosa (Agaricomycetes) Ameliorates Learning and Memory Function in Aluminum Chloride-Induced Amnesia in Mice.

Maitake (Grifola frondosa) is an edible mushroom exhibiting high nutritional value in terms of containing health-beneficial bioactive compounds. Previously, we reported that a protein-bound polysaccharide bioactive component of G. frondosa (PGM) could enhance the expression of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), which is critical for learning and memory. However, the potential benefits of PGM on learning and memory function have never been investigated. In the current study, we aimed to explore the beneficial effect of PGM on learning and memory function in aluminum chloride (AlCl3)-induced amnesia in mice and to explore the underlying mechanisms. Mice were intraperitoneally administered with AlCl3 (60 mg/kg/d) and PGM (5, 10, or 20 mg/kg/d) for 6 weeks consecutively, and then the Morris water maze (MWM) test was conducted to assess the learning and memory function. Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal dentate gyrus (DG). The expression of p-Tau (Ser396), Tau, p-GluA1 (S845), GluA1, and brain-derived neurotrophic factor (BDNF) proteins was evaluated with western blot. We found that PGM (5 and 10 mg/kg/d) significantly improved learning and memory function and attenuated histopathological abnormalities in the hippocampal DG region in the AlCl3-treated mice. Furthermore, PGM treatment significantly enhanced the level of AMPAR and BDNF in the hippocampus, while suppressing the tau protein hyperphosphorylation at the Ser396 site. These findings indicated that PGM could significantly attenuate the AlCl3-induced amnesia through the synergistic action of its active component on tau pathology, AMPAR and BDNF signaling pathway.