Natural products derived from plants, as well as their bioactive compounds, have been extensively studied in recent years for their therapeutic potential in a variety of neurodegenerative diseases (NDs), including Alzheimer’s (AD), Huntington’s (HD), and Parkinson’s (PD) disease. These diseases are characterized by progressive dysfunction and loss of neuronal structure and function. There has been little progress in designing efficient treatments, despite impressive breakthroughs in our understanding of NDs. In the prevention and therapy of NDs, the use of natural products may provide great potential opportunities; however, many clinical issues have emerged regarding their use, primarily based on the lack of scientific support or proof of their effectiveness and patient safety. Since neurodegeneration is associated with a myriad of pathological processes, targeting multi-mechanisms of action and neuroprotection approaches that include preventing cell death and restoring the function of damaged neurons should be employed. In the treatment of NDs, including AD and PD, natural products have emerged as potential neuroprotective agents. This current review will highlight the therapeutic potential of numerous natural products and their bioactive compounds thatexert neuroprotective effects on the pathologies of NDs.

Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used cholesterol-lowering drugs. Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. The objective here was to elucidate the molecular mechanism by which statins induce lymphoma cells death. Statins (atorvastatin, fluvastatin and simvastatin) treatment enhanced the DNA fragmentation and the activation of proapoptotic members such as caspase-3, PARP and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells, which was accompanied by inhibition of cell survival. Both increase in levels of reactive oxygen species (ROS) and activation of p38 MAPK and decrease in mitochondrial membrane potential and activation of Akt and Erk pathways were observed in statin-treated lymphoma cells. Statin-induced cytotoxic effects, DNA fragmentation and changes of activation of caspase-3, Akt, Erk and p38 were blocked by antioxidant (N-acetylcysteine) and metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggests that HMG-CoA reductase inhibitors induce lymphoma cells apoptosis by increasing intracellular ROS generation and p38 activation and suppressing activation of Akt and Erk pathways, through inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.

Silicon dioxide (SiO₂) nanoparticles (NPs) have been widely used in the biomedical field, such as in drug delivery and gene therapy. However, little is known about the biological effects and potential hazards of SiO₂. Herein, the colloidal SiO₂ NPs with two different sizes (20 nm and 100 nm) and different charges (L-arginine modified: SiO₂^EN20[R], SiO₂^EN100[R]; and negative: SiO2^EN20[-], SiO₂^EN100[-]) were orally administered (750 mg/kg/day) in female C57BL/6 mice for 14 days. Assessments of immunotoxicity include hematology profiling, reactive oxygen species generation and their antioxidant effect, stimulation assays for B- and T-lymphocytes, the activity of natural killer (NK) cells, and cytokine profiling. In vitro toxicity was also investigated in the RAW 264.7 cell line. When the cellularity of mouse spleen was evaluated, there was an overall decrease in the proliferation of B- and T-cells for all the groups fed with SiO₂ NPs. Specifically, the SiO₂^EN20(-) NPs showed the most pronounced reduction. In addition, the nitric oxide production and NK cell activity in SiO₂ NP-fed mice were significantly suppressed. Moreover, there was a decrease in the serum concentration of inflammatory cytokines such as interleukin (IL)-1Β, IL-12 (p70), IL-6, tumor necrosis factor-α, and interferon-γ. To elucidate the cytotoxicity mechanism of SiO₂ in vivo, an in vitro study using the RAW 264.7 cell line was performed. Both the size and charge of SiO₂ using murine macrophage RAW 264.7 cells decreased cell viability dose-dependently. Collectively, our data indicate that different sized and charged SiO₂ NPs would cause differential immunotoxicity. Interestingly, the small-sized and negatively charged SiO₂ NPs showed the most potent in vivo immunotoxicity by way of suppressing the proliferation of lymphocytes, depressing the killing activity of NK cells, and decreasing proinflammatory cytokine production, thus leading to immunosuppression.

Oxidative stress (OS) and neuroinflammatory stress affect many neurological disorders. Despite the clinical significance of oxidative damage in neurological disorders, still, no effective and safe treatment methods for neuro diseases are available. With this, molecular hydrogen (H₂) has been recently reported as an antioxidant and anti-inflammatory agent to treat several oxidative stress-related diseases. In animal and human clinical trials, the routes for H₂ administration are mainly categorized into three types: H₂ gas inhalation, H₂ water dissolving, and H₂-dissolved saline injection. This review explores some significant progress in research on H₂ use in neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, neonatal disorders of the brain, and other NDs (retinal ischemia and traumatic brain injury). Even though most neurological problems are not currently curable, these studies have shown the therapeutic potential for prevention, treatment, and mitigation of H₂ administration. Several possible H₂-effectors, including cell signaling molecules and hormones, which prevent OS and inflammation, will also be addressed. However, more clinical and other related studies are required to evaluate the direct H₂ target molecule.

Purpose. This study was performed to evaluate antifatigue effect of hydrogen water (HW) drinking in chronic forced exercise mice model. Materials and Methods. Twelve-week-old C57BL6 female mice were divided into nonstressed normal control (NC) group and stressed group: (purified water/PW-treated group and HW-treated group). Stressed groups were supplied with PW and HW, respectively, ad libitum and forced to swim for the stress induction every day for 4 consecutive weeks. Gross antifatigue effects of HW were assessed by swimming endurance capacity (once weekly for 4 wk), metabolic activities, and immune-redox activities. Metabolic activities such as blood glucose, lactate, glycogen, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) as well as immune-redox activities such as reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), catalase, and the related cytokines were evaluated to elucidate underlying mechanism. Blood glucose and lactate were measured at 0 wk (before swimming) and 4 wk (after swimming). Results. HW group showed a higher swimming endurance capacity (p<0.001) than NC and PW groups. Positive metabolic effects in HW group were revealed by the significant reduction of blood glucose, lactate, and BUN in serum after 4 wk (p<0.01, resp.), as well as the significant increase of liver glycogen (p<0.001) and serum LDH (p<0.05) than PW group. In parallel, redox balance was represented by lower NO in serum (p<0.01) and increased level of GPx in both serum and liver (p<0.05) than PW group. In line, the decreased levels of serum TNF-α (p<0.01), IL-6, IL-17, and liver IL-1β (p<0.05) in HW group revealed positive cytokine profile compared to PW and NC group. Conclusion. This study shows antifatigue effects of HW drinking in chronic forced swimming mice via metabolic coordination and immune-redox balance. In that context, drinking HW could be applied to the alternative and safety fluid remedy for chronic fatigue control.

This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO₂^EN,20(-) (20 nm) or SiO₂^EN,100(-) (100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO₂ particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO₂ particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO₂^EN,20(-) (20 nm) or SiO₂^EN,100(-) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO₂^EN,20(-) and SiO₂^EN,100(-) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex.