Luteolin alleviates cognitive impairment in Alzheimer’s disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation

Kou, Jiejian; Shi, Jun-Zhuo; He, Yangyang; Hao, Jie; Zhang, Haiyu; Dong-mei, Luo; Song, Junke; Yi, Yan; Xie, Xinmei; Du, Guanhua; Pang, Xiaobin

doi:10.1038/s41401-021-00702-8

Cited by 86 publications

(57 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once the mice found the platform, it would stay thereon for a minimum of 5 s. For any mice incapable of finding the platform within the designated time, guidance was given to reach and maintain thereon for 10 s. The platform was withdrawn from the pool on the 6th d for probe testing to test memory consolidation. The cut-off time for probe test was 90 s. The time and distance spent by each mouse in the target quadrant were recorded [ 40 ]. Data documentation was accomplished with the ZS-001 analyzer (Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

et al. 2022

Self Cite

View full text Add to dashboard Cite

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

show abstract

Section: Methodsmentioning

confidence: 99%

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the specific case of luteolin and its glycoside form, the overall scientific data regarding their biological effects suggests an impacting role for these natural compounds by negatively modulating pro-inflammatory and pro-oxidant signaling. Indeed, chronic inflammation, ROS production, and lipid/protein oxidation have been found in the onset of several human diseases such as psoriasis; atherosclerosis; cardiovascular, metabolic, and neurodegenerative disorders; and even in aging [ 1 , 9 , 21 ]. Luteolin and its glycoside have been described to regulate NF-κB, MAPK, and JAK/STAT pathways, modifying the effects induced by different pro-inflammatory cytokines such as TLRs, TNF, IL-1TNF, IL-1, and IL-6.…”

Section: Discussionmentioning

confidence: 99%

“…In sum, flavonoids are molecules with a series of beneficial effects, exerting anti-inflammatory [ 6 , 9 ], antioxidant [ 9 ], pro-apoptotic [ 19 ], anti-aging [ 1 , 20 ], neuroprotective [ 21 ], anti-cancer [ 22 ], antimicrobial [ 23 , 24 , 25 ], antiviral [ 26 , 27 , 28 ], anti-parasitic [ 28 , 29 ], anti-angiogenic [ 9 ], cardioprotective [ 30 ], and antidiabetic [ 31 ] properties.…”

Section: Flavonoids In Nature and Chemical Structurementioning

confidence: 99%

See 1 more Smart Citation

Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside

et al. 2022

View full text Add to dashboard Cite

Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, and other organoleptic characteristics, as well as contributing to important nutritional aspects. Beyond these characteristics, due to their biochemical properties and characteristics, they can be considered bioactive compounds. Several interesting studies have demonstrated their biological activity in different cellular and physiological processes in high-order organisms including humans. The flavonoid molecular structure confers the capability of reacting with and neutralizing reactive oxygen species (ROS), behaving as scavengers in all processes generating this class of molecules, such as UV irradiation, a process widely present in plant physiology. Importantly, the recent scientific literature has demonstrated that flavonoids, in human physiology, are active compounds acting not only as scavengers but also with the important role of counteracting the inflammation process. Among the wide variety of flavonoid molecules, significant results have been shown by investigating the role of the flavones luteolin and luteolin-7-O-glucoside (LUT-7G). For these compounds, experimental results demonstrated an interesting anti-inflammatory action, both in vitro and in vivo, in the interaction with JAK/STAT3, NF-κB, and other pathways described in this review. We also describe the effects in metabolic pathways connected with inflammation, such as cellular glycolysis, diabetes, lipid peroxidation, and effects in cancer cells. Moreover, the inhibition of inflammatory pathway in endothelial tissue, as well as the NLRP3 inflammasome assembly, demonstrates a key role in the progression of such phenomena. Since these micronutrient molecules can be obtained from food, their biochemical properties open new perspectives with respect to the long-term health status of healthy individuals, as well as their use as a coadjutant treatment in specific diseases.

show abstract

“…This effect has been explained by the ability of luteolin to suppress in a dose-dependent manner the expression of pro-inflammatory and pro-apoptotic genes hence shifting the microglial transcriptome toward an anti-inflammatory phenotype ( Dirscherl et al, 2010 ). Recently, it has been reported that luteolin is able to improve memory deficits in a mouse model of AD by inhibiting astrocyte overactivation and neuroinflammation and by reducing endoplasmic reticulum (ER) stress ( Kou et al, 2021 ). In agreement, luteolin has been demonstrated to improve cognitive abilities in a mouse model of vascular dementia by modulating the expression of pro-inflammatory and pro-apoptotic proteins and by stimulating neurogenesis ( Siracusa et al, 2017 ; Cordaro et al, 2020 ).…”

Section: Plant-derived Natural Compounds As Multi-target Disease-modi...mentioning

confidence: 99%

Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes

et al. 2022

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation, neuroinflammation and oxidative stress. Nonetheless, the therapeutic strategies conceived thus far to treat AD neurodegeneration have proven unsuccessful, probably due to the use of single-target drugs unable to arrest the progressive deterioration of brain functions. For this reason, the theoretical description of the AD etiology has recently switched from over-emphasizing a single deleterious process to considering AD neurodegeneration as the result of different pathogenic mechanisms and their interplay. Moreover, much relevance has recently been conferred to several comorbidities inducing insulin resistance and brain energy hypometabolism, including diabetes and obesity. As consequence, much interest is currently accorded in AD treatment to a multi-target approach interfering with different pathways at the same time, and to life-style interventions aimed at preventing the modifiable risk-factors strictly associated with aging. In this context, phytochemical compounds are emerging as an enormous source to draw on in the search for multi-target agents completing or assisting the traditional pharmacological medicine. Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.

show abstract

Luteolin alleviates cognitive impairment in Alzheimer’s disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation

Cited by 86 publications

References 46 publications

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

Cornuside Is a Potential Agent against Alzheimer’s Disease via Orchestration of Reactive Astrocytes

Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside

Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes

Contact Info

Product

Resources

About