Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimers disease DOI Creative Commons
Zhi Tang,

Tong-Tong Sha,

Yun-sheng WANG

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

Introduction Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer′s disease (AD). Isoliquiritigenin, a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on stress. Here, we assessed neuroprotective isoliquiritigenin streptozotocin-injected mouse model. Method Molecular docking analysis performed for with mTOR ERK2. The mice (n = 27, male) were intracerebroventricularly injected streptozotocin, treated (intraperitoneal, 2 days) using Morris water maze. Oxidative stress, tau phosphorylation, synaptic impairment evaluated cortex hippocampal tissues by biochemical assays immunofluorescence staining. Results Isoliquiritigenin treatment mitigated spatial memory capacity alleviated phosphorylation at Ser396; production reactive oxygen species; fission proteins Mfn1 Mfn2; neuronal loss; (PSD95, SNAP25). reduced levels Ser2448 ERK1/2 T202/Y204 upregulated level GSK-3βSer9 hippocampus mice. Conclusion In conclusion, our findings suggest that ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, decreasing ERK activity increasing GSK-3β activity.

Язык: Английский

Myricetin ameliorates cognitive impairment in 3×Tg Alzheimer’s disease mice by regulating oxidative stress and tau hyperphosphorylation DOI Creative Commons
Li Wang, Zhi Tang, Bo Li

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 116963 - 116963

Опубликована: Июнь 17, 2024

Alzheimer's disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro vivo. Here, we aimed elucidate the mechanism pathways involved protective effect of myricetin.

Язык: Английский

Процитировано

4
The role of gastrodin in the management of CNS‐related diseases: Underlying mechanisms to therapeutic perspectives DOI
Xirui He,

Xufei Chen,

Yan Yang

и другие.

Phytotherapy Research, Год журнала: 2024, Номер 38(11), С. 5107 - 5133

Опубликована: Авг. 15, 2024

Abstract Central nervous system (CNS)‐related diseases have a high mortality rate, are serious threat to physical and mental health, always been an important area of research. Gastrodin, the main active metabolite Gastrodia elata Blume, used in Chinese medicine food, has wide range pharmacological effects, mostly related CNS disorders. This review aims systematically summarize discuss effects underlying mechanisms gastrodin treatment diseases, assess its potential for further development as lead drug both biomedicine traditional medicine. Studies on indicate that it may exert anti‐neurodegenerative, cerebrovascular protective, ameliorative diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression anxiety, sleep disorders through various mechanisms. To date, 110 products approved clinical use, but multicenter case–control studies relatively scarce. Preclinical confirmed can be treat CNS‐related However, concerns need addressed context likely non‐specific, assay interfering when is studied using vitro silico approaches, calling systematic assessment evidence date. High‐quality trials should priority evaluate therapeutic safety efficacy gastrodin. Further experimental research appropriate vivo models also needed, focusing neurodegenerative cerebral ischemic hypoxic brain damage caused by methamphetamine or heavy metals, epilepsy.

Язык: Английский

Процитировано

4
Gastrodin Ameliorates Tau Pathology and BBB Dysfunction in 3xTg‐AD Transgenic Mice by Regulating the ADRA1/NF‐κB/NLRP3 Pathway to Reduce Neuroinflammation DOI Open Access
Bo Li, Li Wang, Yan Xiao

и другие.

Phytotherapy Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

ABSTRACT Background and aim: Gastrodin, an active compound derived from the traditional Chinese herbal medicine Gastrodia, demonstrates a variety of pharmacological effects, particularly in enhancement neural functions. Thus, aim this study is to explore therapeutic effects gastrodin on Alzheimer's disease (AD) its underlying molecular mechanisms. Experimental procedure: Cognitive function was assessed via Morris water maze Y‐maze tests. Tau pathology, neuroinflammation, BBB dysfunction were analyzed using various techniques, including Western blot, immunohistochemistry, ELISA. ADRA1 overexpression induced by lentiviral infection, gastrodin's impact NF‐κB p65, NLRP3, IL‐1β, IL‐18 levels evaluated. Key results: In vivo experiment, enhanced learning spatial memory 3xTg‐AD mice, as well reducing p‐Tau protein expression hippocampus cortex. Gastrodin inhibited ADRA1/NF‐κB/NLRP3 pathway, which decreased glial cell activation inflammatory cytokines IL‐1β IL‐18, improving neuron function. vitro NF‐κB/NLRP3 pathway due prevented Aβ 42 ‐induced increase SH‐SY5Y cells. It also reduced cytokine release, restoring tight junction bEnd.3 Conclusions implications: ameliorates abilities alleviating neuroinflammation tau structure neurons BBB, suggesting that may serve effective drug for treatment AD.

Язык: Английский

Процитировано

0
Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer's Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity DOI Creative Commons
Li Wang, Bo Li, Zhi Tang

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(3)

Опубликована: Март 1, 2025

The pathogenesis of Alzheimer's disease (AD) remains incompletely elucidated, and there is a notable deficiency in effective safe therapeutic interventions. influence brain matrix viscoelasticity on the progression AD has frequently been underestimated. It imperative to elucidate these overlooked pathogenic factors innovate novel strategies for AD. Gastrodin, bioactive constituent derived from traditional Chinese medicinal herb Gastrodia elata, exhibits range pharmacological properties, notably enhancement neural function. Nevertheless, underlying mechanisms its action remain insufficiently elucidated. Consequently, this study seeks examine effects gastrodin context AD, with particular emphasis potential viscoelastic properties matrix. This employs methodologies, including Morris water maze test, Y-maze spontaneous alternation atomic force microscopy (AFM), immunofluorescence, transmission electron microscopy, molecular docking, Cellular Thermal Shift Assay (CETSA), demonstrate that mitigates tau pathology by modulating FERMT2, thereby reversing deterioration mechanical brain. Gastrodin administration via gavage demonstrated mitigate cognitive decline associated attenuate hyperphosphorylation protein hippocampus cortex, ameliorate synaptic damage. Additionally, was observed counteract reduction 3xTg-AD mice, as evidenced upregulation extracellular components pertinent viscoelasticity, collagen types I IV. Furthermore, docking CETSA revealed strong binding affinity between FERMT2. treatment resulted FERMT2 fluorescence intensity, which selectively expressed astrocytes. contributed restoration blood-brain barrier (BBB) modulated expression levels inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), metallopeptidase 8 (MMP8). pathology, enhancing learning memory mouse models. effect may be mediated through modulation cerebral mechanosensor facilitates structure process potentially linked maintenance BBB integrity factor release.

Язык: Английский

Процитировано

0
mTOR inhibition alleviated tau phosphorylation-induced mitochondrial impairment, oxidative stress, and cognitive impairment DOI Creative Commons
Zhi Tang, Min Guo,

Yuanting Ding

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 24, 2024

Aim: Hyperphosphorylated tau plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Whether mammalian target rapamycin (mTOR) directly interacts with Tau protein at Ser214, Ser356 and Thr231 is not clear. This study aimed to investigate whether mTOR-regulated phosphorylation disrupts mitochondrial dynamics function rapamycin, an mTOR inhibitor, can modulate levels attenuate AD-related alterations. Methods: Adeno-associated virus (AAV) vectors were used intracranially deliver TauS214E/T231E/S356E (Tau3E) variant into 2-month-old C57BL/6 mice. The mice intraperitoneally administered inhibitor for one week, followed by assessment via Morris water maze test. Western blot analysis, immunofluorescence staining, flow cytometry employed measure expression mTOR, p70S6K, tau; dynamics; reactive oxygen species (ROS) HT22 cells mouse model overexpressing Tau3E, as well postmortem brain tissues from AD patients. Results: p-mTORS2448 colocalized p-TauSer214, p-TauSer356, p-TauThr231 hippocampal CA3 region Tau3E presented elevated p-mTOR, downstream p-p70S6K, ROS production; fragmentation; p-TauThr231. Rapamycin treatment partially mitigated cognitive molecular alterations Conclusion: revealed causal link between Ser356, p-Thr231 upregulation impairments ROS, dysfunction function. Treatment using (i.p.) alleviate impairment, reduce p-Tau restore homeostasis, neuronal loss impairment

Язык: Английский

Процитировано

0
Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimers disease DOI Creative Commons
Zhi Tang,

Tong-Tong Sha,

Yun-sheng WANG

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

Introduction Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer′s disease (AD). Isoliquiritigenin, a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on stress. Here, we assessed neuroprotective isoliquiritigenin streptozotocin-injected mouse model. Method Molecular docking analysis performed for with mTOR ERK2. The mice (n = 27, male) were intracerebroventricularly injected streptozotocin, treated (intraperitoneal, 2 days) using Morris water maze. Oxidative stress, tau phosphorylation, synaptic impairment evaluated cortex hippocampal tissues by biochemical assays immunofluorescence staining. Results Isoliquiritigenin treatment mitigated spatial memory capacity alleviated phosphorylation at Ser396; production reactive oxygen species; fission proteins Mfn1 Mfn2; neuronal loss; (PSD95, SNAP25). reduced levels Ser2448 ERK1/2 T202/Y204 upregulated level GSK-3βSer9 hippocampus mice. Conclusion In conclusion, our findings suggest that ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, decreasing ERK activity increasing GSK-3β activity.

Язык: Английский

Процитировано

0