Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer’s disease

Yu, Wenjun; An, Shengjun; Shao, Tie‐Mei; Xu, Hongjun; Chen, Hong‐Xu; Ning, JunDa; Zhou, Yongjie; Chai, Xin‐Sheng

doi:10.18632/aging.102522

Cited by 23 publications

(14 citation statements)

References 52 publications

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“…In particular, Aβ plaques found in the AD cortex and hippocampi are associated with iron deposits and ferritin [37][38][39]. In accordance with previous studies of AD model mice [40][41][42], we demonstrated significant increases of ferritin in the cortex of 7-month-old 5xFAD mice. Since ferritin is responsible for attenuation and sequestration of free iron [43], ADassociated increases of ferritin levels may indicate elevated labile iron level in the brain.…”

Section: Discussionsupporting

confidence: 91%

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Belaya

Kucháriková

Górová

et al. 2021

IJMS

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Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice. Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle. Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway. These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice.

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Section: Discussionsupporting

confidence: 91%

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Belaya

Kucháriková

Górová

et al. 2021

IJMS

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“…Additionally, transferrin receptor protein 1 (Tfr1), the major vehicle of iron delivery into cells, also was significantly upregulated in AD mice. Treatment with the active compounds of herbs ameliorate impaired cognition and this beneficial effect is associated with reduced impairment of iron metabolism ( Yu et al, 2019 ; Ma et al, 2021 ). Thus, enhancing iron export or inhibiting iron transport could be a promising strategy to reduce the ferroptotic cell death in this disease.…”

Section: Ferroptosis-related Signaling Pathways In Admentioning

confidence: 99%

Ferroptosis, a Potential Therapeutic Target in Alzheimer’s Disease

Chen

Jiang

et al. 2021

Front. Cell Dev. Biol.

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Cell death is a common phenomenon in the progression of Alzheimer’s disease (AD). However, the mechanism of triggering the death of neuronal cells remains unclear. Ferroptosis is an iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Moreover, several hallmarks of AD pathogenesis were consistent with the characteristics of ferroptosis, such as excess iron accumulation, elevated lipid peroxides, and reactive oxygen species (ROS), reduced glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels. Besides, some ferroptosis inhibitors can relieve AD-related pathological symptoms in AD mice and exhibit potential clinical benefits in AD patients. Therefore, ferroptosis is gradually being considered as a distinct cell death mechanism in the pathogenesis of AD. However, direct evidence is still lacking. In this review, we summarize the features of ferroptosis in AD, its underlying mechanisms in AD pathology, and review the application of ferroptosis inhibitors in both AD clinical trials and mice/cell models, to provide valuable information for future treatment and prevention of this devastating disease.

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“…First, PUE can generate multiple beneficial effects by manipulation of different signal pathways, but we primarily focused on PI3K/Akt signal activation‐mediated suppression of the NF‐κB pathway. Hence, PUE may exert neuroprotective effects by other signal pathways such as the Nrf2 signaling pathway 32 and iron metabolism pathway 25 . Second, the collagenase‐induced rat ICH model itself cannot completely mirror the pathophysiological process of ICH patients.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, PUE may exert neuroprotective effects by other signal pathways such as the Nrf2 signaling pathway 32 and iron metabolism pathway. 25 Second, the collagenase‐induced rat ICH model itself cannot completely mirror the pathophysiological process of ICH patients. Thus, results from our research might need to be further verified with other ICH models such as autologous blood and hemoglobin injection and be carefully explained.…”

Section: Discussionmentioning

confidence: 99%

“…Puerarin (PUE), as a primary bioactive compound of Pueraria lobata roots, 7 , 8 has exhibited potently neuroprotective activity in multiple central nervous system (CNS) disorders, including stroke, 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 subarachnoid hemorrhage (SAH), 17 traumatic brain injury (TBI), 18 spinal cord injury (SCI), 19 , 20 , 21 , 22 , 23 Alzheimer's disease (AD), 24 , 25 , 26 , 27 , 28 and Parkinson's disease (PD). 29 , 30 , 31 , 32 , 33 Research studies have shown that PUE can generate brain‐protective effects by activating the phosphatidylinositol 3‐kinase (PI3K)/Akt signal against acute CNS disorders 18 , 19 , 34 and neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

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Puerarin attenuates intracerebral hemorrhage‐induced early brain injury possibly by PI3K/Akt signal activation‐mediated suppression of NF‐κB pathway

Zeng

Zheng

Chen

et al. 2021

J Cellular Molecular Medi

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Intracerebral hemorrhage (ICH) can induce intensively oxidative stress, neuroinflammation, and brain cell apoptosis. However, currently, there is no highly effective treatment available. Puerarin (PUE) possesses excellent neuroprotective effects by suppressing the NF‐κB pathway and activating the PI3K/Akt signal, but its role and related mechanisms in ICH‐induced early brain injury (EBI) remain unclear. In this study, we intended to observe the effects of PUE and molecular mechanisms on ICH‐induced EBI. ICH was induced in rats by collagenase IV injection. PUE was intraperitoneally administrated alone or with simultaneously intracerebroventricular injection of LY294002 (a specific inhibitor of the PI3K/Akt signal). Neurological deficiency, histological impairment, brain edema, hematoma volume, blood–brain barrier destruction, and brain cell apoptosis were evaluated. Western blot, immunohistochemistry staining, reactive oxygen species (ROS) measurement, and enzyme‐linked immunosorbent assay were performed. PUE administration at 50 mg/kg and 100 mg/kg could significantly reduce ICH‐induced neurological deficits and EBI. Moreover, PUE could notably restrain ICH‐induced upregulation of the NF‐κB pathway, pro‐inflammatory cytokines, ROS level, and apoptotic pathway and activate the PI3K/Akt signal. However, LY294002 delivery could efficaciously weaken these neuroprotective effects of PUE. Overall, PUE could attenuate ICH‐induced behavioral defects and EBI possibly by PI3K/Akt signal stimulation‐mediated inhibition of the NF‐κB pathway, and this made PUE a potential candidate as a promising therapeutic option for ICH‐induced EBI.

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Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer’s disease

Cited by 23 publications

References 52 publications

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Ferroptosis, a Potential Therapeutic Target in Alzheimer’s Disease

Puerarin attenuates intracerebral hemorrhage‐induced early brain injury possibly by PI3K/Akt signal activation‐mediated suppression of NF‐κB pathway

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