Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice

Ruan, Yingying; Zhai, Wei; Shi, Xiaomeng; Zhang, Lu; Hu, Yanli

doi:10.1007/s11011-016-9857-3

Cited by 11 publications

(7 citation statements)

References 37 publications

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“…Numerous studies have observed that the phosphorylation of some sites of tau is significantly increased in APP/PS1 mice despite the lack of mature tangles. 51 , 52 , 53 Consistent with previous studies, we found that the level of tau phosphorylation at Thr181 and Ser396 was increased in the hippocampus (Figure 6B,D ) and cortex (Figure 6F,H ) of the APP/PS1 mice, but similar results were not observed for tau phosphorylation at Ser202 (Figure 6C,G ). The role of HDAC2/3 in tau pathway is not well‐defined.…”

Section: Discussionsupporting

confidence: 91%

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Apicidin attenuates memory deficits by reducing the Aβ load inAPP/PS1mice

et al. 2023

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Aims Amyloid beta (Aβ) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic Aβ by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of Aβ in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10. Methods Nine‐month‐old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The Aβ levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting. Results Apicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of Aβ‐enriched plaques, and decreased the levels of soluble and insoluble Aβ40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPPα, and reduced the production of sAPPβ, but did not affect the levels of phosphorylated tau in APP/PS1 mice. Conclusion Apicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of Aβ rather than decreasing the phosphorylation of tau.

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Section: Discussionsupporting

confidence: 91%

“…Numerous studies have observed that the phosphorylation of some sites of tau is significantly increased in APP/PS1 mice despite the lack of mature tangles. [51][52][53] Consistent with previous studies, we found that the level of tau phosphorylation at Thr181…”

Section: Apicidin Treatment Does Not Reduce Tau Phosphorylation In Th...supporting

confidence: 92%

Apicidin attenuates memory deficits by reducing the Aβ load inAPP/PS1mice

et al. 2023

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“…Hyperphosphorylated tau is the primary component of intracellular NFTs, which have an important role in AD pathology ( 2 , 39 ). It has been demonstrated that hyperphosphorylated tau may also result in neuronal death and memory impairment ( 5 , 40 , 41 ). A number of serine phosphorylation sites of tau are elevated in AD mice, including Ser199 and Ser396 ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…Pathologically, accumulation of senile plaques, neurofibrillary tangles (NFTs) and neuronal loss have been observed in the brain cortex and hippocampus of patients with AD ( 2 ). Although the underlying mechanisms have not been fully elucidated, β-amyloid (Aβ) aggregation and tau hyperphosphorylation have been revealed to exhibit key roles in the pathogenesis of AD ( 3 , 4 ), as they are primary components of senile plaques and NFTs, respectively ( 5 , 6 ) and are associated with neuronal loss and memory deficits ( 7 , 8 ). Therefore, potential pharmacological agents targeting the inhibition of these pathological processes may be promising therapeutic approaches in treating AD.…”

Section: Introductionmentioning

confidence: 99%

Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of β‑amyloid production and tau hyperphosphorylation

Zhong

Liu

Zhang³

et al. 2018

Exp Ther Med

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β-amyloid (Aβ) aggregation and tau hyperphosphorylation are considered to be the primary pathological hallmarks of Alzheimer's disease (AD). Targeted inhibition of these pathological processes may provide effective treatments for AD. Accumulating evidence has demonstrated that ellagic acid (EA) exerts neuroprotective effects in several diseases. The present study investigated the effects of EA on AD-associated learning and memory deficits on APP/PS1 double transgenic mice and the underlying mechanisms. APP/PS1 mice or wild-type C57BL/6 mice were intragastrically administered EA (50 mg/kg/day) or vehicle for 60 consecutive days. The learning and memory abilities of mice were investigated using the Morris water maze test. Hippocampal regions were examined for the presence of amyloid plaques, neuronal apoptosis and tau phosphorylation. Expression levels of APP, Aβ, RAC-αserine/threonine-protein kinase and glycogen synthase kinase (GSK)3β in the hippocampus were determined by western blot analysis and ELISA. The results demonstrated that EA treatment ameliorated spatial learning and memory impairment in APP/PS1 mice and significantly reduced neuronal apoptosis and Aβ deposition in the hippocampus (P<0.05 and P<0.01). In addition, EA significantly inhibited the hyperphosphorylation of tau and significantly decreased the activity of glycogen synthase kinase (GSK)3β (P<0.01), which is involved in tau phosphorylation. Overall, these findings indicated that the beneficial effects of EA on AD-associated cognitive impairments may be attributed to the inhibition of Aβ production and tau hyperphosphorylation, and its beneficial action may be mediated in part, by the RAC-α serine/threonine-protein kinase/GSK3β signaling pathway.

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“…The step-down test was performed as described by Ruan et al (2016) . The error times during training, step-down delay and error times during experiments were recorded.…”

Section: Methodsmentioning

confidence: 99%

Rheum tanguticum Alleviates Cognitive Impairment in APP/PS1 Mice by Regulating Drug-Responsive Bacteria and Their Corresponding Microbial Metabolites

et al. 2021

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Drugs targeting intestinal bacteria have shown great efficacy for alleviating symptoms of Alzheimer’s disease (AD), and microbial metabolites are important messengers. Our previous work indicated that Rheum tanguticum effectively improved cognitive function and reshaped the gut microbial homeostasis in AD rats. However, its therapeutic mechanisms remain unclear. Herein, this study aimed to elaborate the mechanisms of rhubarb for the treatment of AD by identifying effective metabolites associated with rhubarb-responsive bacteria. The results found that rhubarb reduced hippocampal inflammation and neuronal damage in APP/PS1 transgenic (Tg) mice. 16S rRNA sequencing and metabolomic analysis revealed that gut microbiota and their metabolism in Tg mice were disturbed in an age-dependent manner. Rhubarb-responsive bacteria were further identified by real-time polymerase chain reaction (RT-PCR) sequencing. Four different metabolites reversed by rhubarb were found in the position of the important nodes on rhubarb-responsive bacteria and their corresponding metabolites combined with pathological indicators co-network. Furthermore, in vitro experiments demonstrated o-tyrosine not only inhibited the viabilities of primary neurons as well as BV-2 cells, but also increased the levels of intracellular reactive oxygen species and nitric oxide. In the end, the results suggest that rhubarb ameliorates cognitive impairment in Tg mice through decreasing the abundance of o-tyrosine in the gut owing to the regulation of rhubarb-responsive bacteria. Our study provides a promising strategy for elaborating therapeutic mechanisms of bacteria-targeted drugs for AD.

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Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice

Cited by 11 publications

References 37 publications

Apicidin attenuates memory deficits by reducing the Aβ load inAPP/PS1mice

Apicidin attenuates memory deficits by reducing the Aβ load inAPP/PS1mice

Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of β‑amyloid production and tau hyperphosphorylation

Rheum tanguticum Alleviates Cognitive Impairment in APP/PS1 Mice by Regulating Drug-Responsive Bacteria and Their Corresponding Microbial Metabolites

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