Acetyl-L-carnitine confers neuroprotection against lipopolysaccharide (LPS) -induced neuroinflammation by targeting TLR4/NFκB, autophagy, inflammation and oxidative stress

Jamali-Raeufy, Nida; Alizadeh, Fahimeh; Mehrabi, Zhila; Mehrabi, Soraya; Goudarzi, Mina

doi:10.1007/s11011-021-00715-6

Cited by 24 publications

(15 citation statements)

References 42 publications

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“…Systemic LPS exposure and neuroinflammation increase oxidative stress in brain regions such as the hippocampus (Jamali-Raeufy et al, 2021). In the present study, we had no evidence of increased oxidative stress, i.e., increased level of MDA, in the hippocampus and cerebral cortex on the next day of the last LPS administration, while upregulation in the transcript level was observed in several oxidative stress-related genes.…”

Section: Discussioncontrasting

confidence: 75%

Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats

et al. 2023

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This study investigated the role of neuroinflammation in a lipopolysaccharides (LPS)induced cognitive dysfunction model in rats using an antioxidant, α-glycosyl isoquercitrin (AGIQ). Sixweek-old rats were dietary treated with 0.5% (w/w) AGIQ for 38 days, and LPS at 1 mg/kg body weight was administered intraperitoneally once daily on Days 8 and 10. On Day 11, LPS alone increased or tended to increase interleukin-1β and tumor necrosis factor-α in the hippocampus and cerebral cortex. Immunohistochemically, LPS alone increased the number of Iba1 + and CD68 + microglia, and GFAP + astrocytes in the hilus of the hippocampal dentate gyrus (DG). AGIQ treatment decreased or tended to decrease brain proinflammatory cytokine levels and the number of CD68 + microglia in the DG hilus. In the contextual fear conditioning test during Day 34 and Day 38, LPS alone impaired fear memory acquisition, and AGIQ tended to recover this impairment. On Day 38, LPS alone decreased the number of DCX + cells in the neurogenic niche, and AGIQ increased the numbers of PCNA + cells in the subgranular zone and CALB2 + hilar interneurons. Additionally, LPS alone decreased or tended to decrease the number of synaptic plasticity-related FOS + and COX2 + granule cells and AGIQ recovered them. The results suggest that LPS administration induced acute neuroinflammation and subsequent impairment of fear memory acquisition caused by suppressed synaptic plasticity of newborn granule cells following disruptive neurogenesis. In contrast, AGIQ exhibited anti-inflammatory effects and ameliorated LPS-induced adverse effects. These results suggest that neuroinflammation is a key factor in the development of LPS-induced impairment of fear memory acquisition.

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Section: Discussioncontrasting

confidence: 75%

Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats

et al. 2023

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“…Bif.animalis F1-7 intervention. Studies had reported that ALC could improve inflammatory response and oxidative stress through TLR4/NFκB pathway [45]. It could also reduce atherosclerotic plaque accumulation by acting on CRP and TNF-α [46].…”

Section: Discussionmentioning

confidence: 99%

Metabolite acetyl- L-carnitine participates in Bifidobacterium animalis F1-7 to ameliorate atherosclerotic inflammation by downregulating theTLR4/NF-κB pathway

Liu¹,

Zhang²,

Tian³

et al. 2024

Food Science and Human Wellness

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This study aimed to explore the effect of Bif. Animalis F1-7 on the improvement of atherosclerotic inflammation. Arteriosclerosis model ApoE -/mice were orally administered with Bif. Animalis F1-7 for 12 weeks. The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages, and downregulated the expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NFκB) pathway to reduce the levels of inflammatory factors. The widely-targeted metabolomics analysis showed that acetyl-L-carnitine (ALC) in the intestine of atherosclerotic mice was significantly increased after Bif. Animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response. By using ox-LDL induced macrophage foam cells, we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NFκB pathway. Finally, our results revealed that Bif. Animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses, leading to the reduction of plaque accumulation of atherosclerosis.

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“…However, a study reported that the activation of TLR4 by bacterial LPS inhibited autophagy through the MyD88-TAK1-MAPK-dependent phosphorylation of mTOR (Zhou et al, 2018). Another recent study showed that the intraperitoneal injection of LPS promoted neuroinflammation by activating TLR4, inhibiting autophagic markers, and inducing excessive oxidation intermediates (Jamali-Raeufy et al, 2021a). We hypothesize that this opposite result is related to the different concentrations and duration of stimulation or different types of cells used.…”

Section: Tlr4 and Nitroxidative Stress Induce Autophagymentioning

confidence: 88%

Mechanisms of TLR4-Mediated Autophagy and Nitroxidative Stress

Zhang

Huang

Deng

et al. 2021

Front. Cell. Infect. Microbiol.

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Pathogenic infections have badly affected public health and the development of the breeding industry. Billions of dollars are spent every year fighting against these pathogens. The immune cells of a host produce reactive oxygen species and reactive nitrogen species which promote the clearance of these microbes. In addition, autophagy, which is considered an effective method to promote the destruction of pathogens, is involved in pathological processes. As research continues, the interplay between autophagy and nitroxidative stress has become apparent. Autophagy is always intertwined with nitroxidative stress. Autophagy regulates nitroxidative stress to maintain homeostasis within an appropriate range. Intracellular oxidation, in turn, is a strong inducer of autophagy. Toll-like receptor 4 (TLR4) is a pattern recognition receptor mainly involved in the regulation of inflammation during infectious diseases. Several studies have suggested that TLR4 is also a key regulator of autophagy and nitroxidative stress. In this review, we describe the role of TLR4 in autophagy and oxidation, and focus on its function in influencing autophagy-nitroxidative stress interactions.

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Acetyl-L-carnitine confers neuroprotection against lipopolysaccharide (LPS) -induced neuroinflammation by targeting TLR4/NFκB, autophagy, inflammation and oxidative stress

Cited by 24 publications

References 42 publications

Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats

Amelioration of lipopolysaccharides-induced impairment of fear memory acquisition by alpha-glycosyl isoquercitrin through suppression of neuroinflammation in rats

Metabolite acetyl- L-carnitine participates in Bifidobacterium animalis F1-7 to ameliorate atherosclerotic inflammation by downregulating theTLR4/NF-κB pathway

Mechanisms of TLR4-Mediated Autophagy and Nitroxidative Stress

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