Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by progressive loss of memory and cognitive function, and is associated with the deficiency of synaptic acetylcholine, as well as chronic neuroinflmmation. Tacrine, a potent acetylcholinesterase (AChE) inhibitor, was previously a prescribed clinical therapeutic agent for AD, but it was recently withdrawn because it caused widespread hepatotoxicity. Hydrogen sulfide (H2S) has neuroprotective, hepatoprotective, and anti-inflammatory effects. In this study, we synthesized a new compound, a tacrine–H2S donor hybrid (THS) by introducing H2S-releasing moieties (ACS81) to tacrine. Subsequently, pharmacological and biological evaluations of THS were conducted in the aluminum trichloride (AlCl3)-induced AD mice model. We found that THS (15 mmol/kg) improved cognitive and locomotor activity in AD mice in the step-through test and open field test, respectively. THS showed strong AChE inhibitory activity in the serum and hippocampus of AD mice and induced increased hippocampal H2S levels. Furthermore, THS reduced mRNA expression of the proinflammatory cytokines, TNF-α, IL-6, and IL-1β and increased synapse-associated proteins (synaptophysin and postsynaptic density protein 95) in the hippocampus of AD mice. Importantly, THS, unlike tacrine, did not increase liver transaminases (alanine transaminase and aspartate transaminase) or proinflammatory cytokines, indicating THS is much safer than tacrine. Therefore, the multifunctional effects of this new hybrid compound of tacrine and H2S indicate it is a promising compound for further research into the treatment of AD.

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Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p < 0.05 or p < 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p < 0.05 or p < 0.01) and nuclear factor-kappa B (NF-κB p65; p < 0.05 or p < 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p < 0.05 or p < 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p < 0.05 or p < 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p < 0.05 or p < 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice.

Luteolin, a flavonoid isolated from Cirsium japonicum, has antioxidant, anti-inflammatory and neuroprotective activities. Our previous studies brought a prospect that luteolin benefited diabetic rats with cognitive impairments. In this study, we examined whether luteolin could suppress the inflammatory cytokines, thus increasing synapse-associated proteins in streptozotocin (STZ)-induced diabetes in rat models. The model rats underwent luteolin treatment for 8 consecutive weeks, followed by assessment of cognitive performances with MWM test. Nissl staining was employed to assess the neuropathological changes in the hippocampus and the effects of luteolin on diabetic rats. With animals sacrificed, expressions of inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and synapse-associated proteins including growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were determined. The results affirmed improvement of behavioral performances in the MWM test, downexpression of glycation end products (AGEs) in the plasma and the receptor for advanced glycation end products in the hippocampus, inhibition of IL-1β and TNF-α in both the hippocampus and plasma in diabetic rats. Furthermore, luteolin treatment upregulated the expressions of GAP-43 and SYN in the hippocampus. Thus, luteolin could ameliorate the cognitive dysfunctions in STZ-induced diabetic rat model.

Manganese-oxide and palladium nanoparticle-co-decorated polypyrrole/graphene oxide (MnO2@Pd@PPy/GO) nanoenzyme composites were synthesized, and could be as a novel “theranostic nanoagent” for cancer treatment due to excellent performance.