Fruitless Wolfberry-Sprout Extract Rescued Cognitive Deficits and Attenuated Neuropathology in Alzheimer's Disease Transgenic Mice.

Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aβ leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aβ levels and inhibiting Aβ-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown. The effects of fruitless wolfberry-sprout extract (FWE) on Aβ fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aβ oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aβ40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aβ burden and gliosis was evaluated by immunostaining and immunoblotting, respectively. FWE significantly inhibited Aβ fibrillation and disaggregated the formed Aβ fibrils, lowered Aβ oligomer level and Aβ-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aβ burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice. These findings indicate that FWE is a promising natural agent for AD treatment.

Liu SY ，Lu S ，Yu XL ，Yang SG ，Liu W ，Liu XM ，Wang SW ，Zhu J ，Ji M ，Liu DQ ，Zhang ZP ，Liu RT ... -  《-》

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 ... -  《-》

Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model.

The accumulation of β-amyloid (Aβ) peptide derived from abnormal processing of amyloid precursor protein (APP) is a common pathological hallmark of Alzheimer's disease (AD) brains. In this study, we evaluated the therapeutic effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a well established transgenic mouse model of AD. Two-month-old TgCRND8 mice received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by oral gavage until 6 months old. BBR treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. In addition, enzyme-linked immunosorbent assay (ELISA) measurement showed that there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in brain homogenates of BBR-treated mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau phosphorylation, was significantly inhibited by BBR treatment. We also found that BBR significantly decreased the levels of C-terminal fragments of APP and the hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3 signaling pathway in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a-SwedAPP). Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted.

Durairajan SS ，Liu LF ，Lu JH ，Chen LL ，Yuan Q ，Chung SK ，Huang L ，Li XS ，Huang JD ，Li M ... -  《-》

L-3-n-butylphthalide improves cognitive impairment and reduces amyloid-beta in a transgenic model of Alzheimer's disease.

Peng Y ，Sun J ，Hon S ，Nylander AN ，Xia W ，Feng Y ，Wang X ，Lemere CA ... -  《-》

Effects of the superoxide dismutase/catalase mimetic EUK-207 in a mouse model of Alzheimer's disease: protection against and interruption of progression of amyloid and tau pathology and cognitive decline.

Clausen A ，Xu X ，Bi X ，Baudry M ... -  《-》