Rutin inhibits β-amyloid aggregation and cytotoxicity, attenuates oxidative stress, and decreases the production of nitric oxide and proinflammatory cytokines.

Alzheimer's disease (AD) is a complex, multi-factorial neurodegenerative disease. The aggregation of soluble β-amyloid (Aβ) into fibrillar deposits is a pathological hallmark of AD. The Aβ aggregate-induced neurotoxicity, inflammatory reactions, oxidative stress, and nitric oxide (NO) generation are strongly linked to the etiology of AD. Here, we show that the common dietary flavonoid, rutin, can dose-dependently inhibit Aβ42 fibrillization and attenuate Aβ42-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Moreover, rutin decreases the formation of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), and malondialdehyde (MDA), reduces inducible nitric oxide synthase (iNOS) activity, attenuates mitochondrial damage, increases the glutathione (GSH)/GSSG ratio, enhances the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and modulates the production of proinflammatory cytokines by decreasing TNF-α and IL-1β generation in microglia. Taken together, the actions of rutin on multiple pathogenic factors deserves further investigation for the prevention and treatment of AD.

Wang SW ，Wang YJ ，Su YJ ，Zhou WW ，Yang SG ，Zhang R ，Zhao M ，Li YN ，Zhang ZP ，Zhan DW ，Liu RT ... -  《-》

Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress.

Yu XL ，Li YN ，Zhang H ，Su YJ ，Zhou WW ，Zhang ZP ，Wang SW ，Xu PX ，Wang YJ ，Liu RT ... -  《-》

α-Tocopherol quinone inhibits β-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines.

Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disease. The aggregation of beta-amyloid (Aβ) into extracellular fibrillar deposition is a pathological hallmark of AD. The Aβ aggregate-induced neurotoxicity, inflammatory reactions and oxidative stress are linked strongly to the etiology of AD. The currently available hitting-one-target drugs are insufficient for the treatment of AD. Therefore, finding multipotent agents able to modulate multiple targets simultaneously is attracting more attention. Previous studies indicated that vitamin E or its constituent such as α-tocopherol (α-T) was able to attenuate the effects of several pathogenetic factors in AD. However, ineffective or detrimental results were obtained from a number of clinical trials of vitamin E. Here, we showed that naturally synthesized RRR-α-tocopherol quinone (α-TQ), a main derivative of α-T, could inhibit Aβ42 fibril formation dose-dependently. Further investigations indicated that α-TQ could attenuate Aβ42-induced neurotoxicity toward SH-SY5Y neuroblastoma cells, disaggregate preformed fibrils and interfere with natural intracellular Aβ oligomer formation. Moreover, α-TQ could decrease the formation of reactive oxygen species (ROS) and NO, and modulate the production of cytokines by decreasing TNF-α and IL-1β and increasing IL-4 formation in microglia. Taken together, α-TQ targeting multiple pathogenetic factors deserves further investigation for prevention and treatment of AD.

Yang SG ，Wang WY ，Ling TJ ，Feng Y ，Du XT ，Zhang X ，Sun XX ，Zhao M ，Xue D ，Yang Y ，Liu RT ... -  《-》

Neoechinulin A suppresses amyloid-β oligomer-induced microglia activation and thereby protects PC-12 cells from inflammation-mediated toxicity.

A pathological hallmark of Alzheimer's disease (AD), aggregation and deposition of amyloid-β peptides, has been recognized as a potent activator of microglia-mediated neuroinflammation and neuronal dysfunction. Therefore, downregulation of microglial activation has a significant therapeutic demand. In this study, focus was given to evaluate the ability of neoechinulin A, an indole alkaloid isolated from marine-derived Microsporum sp., to attenuate microglial activation by oligomeric amyloid-β 1-42 (Aβ42). Neoechinulin A treatment significantly inhibited the generation of reactive oxygen and nitrogen species in Aβ42-activated BV-2 microglia cells. In addition, we found that neoechinulin A significantly suppressed the production of neurotoxic inflammatory mediator tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in activated BV-2 cells. Moreover, the treatment downregulated the protein and gene expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β and IL-6. Further, activated microglia-mediated apoptosis of PC-12 pheochromocytoma cells was significantly repressed by neoechinulin A. The molecular mechanism studies suggested that neoechinulin A may block the phosphorylation of mitogen-activated protein kinase (MAPK) molecule p38, apoptosis signal-regulating kinase 1 (ASK-1) and nuclear translocation of nuclear factor-κB (NF-κB) p65 and p50 subunits. Regulation of these signalling pathways have most probably contributed to the anti-inflammatory activity of neoechinulin A. Collectively, these results suggest that with further studies neoechinulin A have a potential to be developed as a modulator of neuroinflammatory process in AD.

Dewapriya P ，Li YX ，Himaya SW ，Pangestuti R ，Kim SK ... -  《-》

Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles in the brain. Aβ aggregation is closely associated with neurotoxicity, oxidative stress, and neuronal inflammation. The soluble Aβ oligomers are believed to be the most neurotoxic form among all forms of Aβ aggregates. We have previously reported a polyphenol compound rutin that could inhibit Aβ aggregation and cytotoxicity, attenuate oxidative stress, and decrease the production of nitric oxide and proinflammatory cytokines in vitro. In the current study, we investigated the effect of rutin on APPswe/PS1dE9 transgenic mice. Results demonstrated that orally administered rutin significantly attenuated memory deficits in AD transgenic mice, decreased oligomeric Aβ level, increased super oxide dismutase (SOD) activity and glutathione (GSH)/glutathione disulfide (GSSG) ratio, reduced GSSG and malondialdehyde (MDA) levels, downregulated microgliosis and astrocytosis, and decreased interleukin (IL)-1β and IL-6 levels in the brain. These results indicated that rutin is a promising agent for AD treatment because of its antioxidant, anti-inflammatory, and reducing Aβ oligomer activities.

Xu PX ，Wang SW ，Yu XL ，Su YJ ，Wang T ，Zhou WW ，Zhang H ，Wang YJ ，Liu RT ... -  《-》