Neuroinflammation in Alzheimer's disease and beneficial action of luteolin

Delgado, Alejandro; Cholevas, Christos; Tc, Theoharides

doi:10.1002/biof.1714

Cited by 26 publications

(30 citation statements)

References 179 publications

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“…We found that, similar to luteolin, SP600125 reduced the phosphorylation of JNK and its downstream signaling and that inhibition of JNK with Luteolin significantly reduced the expression of JNK and of the inflammatory and apoptotic markers, showing a role of JNK in the neuroprotective effects of Luteolin. The anti-inflammatory effects of Luteolin are in agreement with those reported in previous studies on Luteolin [46]. The inhibition of p-JNK through Luteolin was also confirmed by another study conducted on amyloid beta-treated cortical neurons and LPS-stimulated microglial cells [47,48].…”

Section: Discussionsupporting

confidence: 90%

Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

Ahmad

Ikram

et al. 2021

IJMS

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The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ1–42)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For the development of an AD mouse model, amyloid-beta (Aβ1–42, 5 µL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice’s brain by using a stereotaxic frame. After that, the mice were treated with Luteolin for two weeks at a dose of 80 mg/kg/day. To monitor the biochemical changes, we conducted western blotting and immunofluorescence analysis. According to our findings, the infusion of amyloid-beta activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental mice; these changes were significantly inhibited in Aβ1–42 + Luteolin-treated mice. Likewise, we also checked the expression of inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB p65 (Ser536), tissue necrosis factor (TNF-α), and Interleukin1-β (IL-1β), in Aβ1–42-injected mice brain, which was attenuated in Aβ1–42 + Luteolin-treated mice brains. Further, we investigated the expression of pro- and anti-apoptotic cell death markers such as Bax, Bcl-2, Caspase-3, and Cox-2, which was significantly reduced in Aβ1–42 + Lut-treated mice brains compared to the brains of the Aβ-injected group. The results also indicated that with the administration of Aβ1–42, the expression levels of β-site amyloid precursor protein cleaving enzyme (BACE-1) and amyloid-beta (Aβ1–42) were significantly enhanced, while they were reduced in Aβ1–42 + Luteolin-treated mice. We also checked the expression of synaptic markers such as PSD-95 and SNAP-25, which was significantly enhanced in Aβ1–42 + Lut-treated mice. To unveil the underlying factors responsible for the protective effects of Luteolin against AD, we used a specific JNK inhibitor, which suggested that Luteolin reduced Aβ-associated neuroinflammation and neurodegeneration via inhibition of JNK. Collectively, our results indicate that Luteolin could serve as a novel therapeutic agent against AD-like pathological changes in mice.

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Section: Discussionsupporting

confidence: 90%

Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

Ahmad

Ikram

et al. 2021

IJMS

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“…Resveratrol has been found to modulate levels of Aβ and certain inflammatory markers in AD patients [172]. Luteolin can play a prophylactic role against AD [173]. Additionally, moderate activation of microglia is thought to have beneficial effects in removing neurotoxins, cellular debris, and dying cells or in promoting neuronal survival.…”

Section: Potential Strategies Involving Cytokines For Management Of Admentioning

confidence: 99%

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Ogunmokun,

Dewanjee,

Chakraborty

et al. 2021

Cells

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Alzheimer’s disease (AD) is one of the most prominent neurodegenerative diseases, which impairs cognitive function in afflicted individuals. AD results in gradual decay of neuronal function as a consequence of diverse degenerating events. Several neuroimmune players (such as cytokines and growth factors that are key players in maintaining CNS homeostasis) turn aberrant during crosstalk between the innate and adaptive immunities. This aberrance underlies neuroinflammation and drives neuronal cells toward apoptotic decline. Neuroinflammation involves microglial activation and has been shown to exacerbate AD. This review attempted to elucidate the role of cytokines, growth factors, and associated mechanisms implicated in the course of AD, especially with neuroinflammation. We also evaluated the propensities and specific mechanism(s) of cytokines and growth factors impacting neuron upon apoptotic decline and further shed light on the availability and accessibility of cytokines across the blood-brain barrier and choroid plexus in AD pathophysiology. The pathogenic and the protective roles of macrophage migration and inhibitory factors, neurotrophic factors, hematopoietic-related growth factors, TAU phosphorylation, advanced glycation end products, complement system, and glial cells in AD and neuropsychiatric pathology were also discussed. Taken together, the emerging roles of these factors in AD pathology emphasize the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

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“…Both flavonoids have broad anti-viral properties, inhibit entry of the virus into host cells, 108,147,148 inhibit neuroinflammation, 149 and reduce cognitive decline. 150 Furthermore, luteolin better penetrates into the brain, inhibits both microglia 151,152 and mast cells, 153,154 and has been reported to reduce neuroinflammation 145,155,156 and cognitive dysfunction, 157,158 including Alzheimer's disease in humans 159,160 and in animal models. 161 Luteolin and quercetin are difficult to absorb after oral administration, 162 but their pharmacokinetics are greatly improved in liposomal preparations using olive pomace oil.…”

Section: Treatment Approachesmentioning

confidence: 99%

Long‐COVID syndrome‐associated brain fog and chemofog: Luteolin to the rescue

Cholevas²,

Polyzoidis³

et al. 2021

BioFactors

Self Cite

164

140

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COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

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Neuroinflammation in Alzheimer's disease and beneficial action of luteolin

Cited by 26 publications

References 179 publications

Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ1–42-Induced Alzheimer’s Disease

The Potential Role of Cytokines and Growth Factors in the Pathogenesis of Alzheimer’s Disease

Long‐COVID syndrome‐associated brain fog and chemofog: Luteolin to the rescue

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