Neohesperidin dihydrochalcone down-regulates MyD88-dependent and -independent signaling by inhibiting endotoxin-induced trafficking of TLR4 to lipid rafts

Xia, Xiaomin; Fu, Juanli; Song, Xiufang; Shi, Qiong; Su, Chuanyang; Song, Erqun; Song, Yang

doi:10.1016/j.freeradbiomed.2015.08.023

Cited by 31 publications

(19 citation statements)

References 49 publications

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“…In our studies, AA treatment effectively decreased the ALT and AST levels in sera and increased survival rate in the L/D-induced mouse model. Conversely, previous studies have indicated that L/D-induced macrophages in FHF mice provoke the release of numerous inflammatory factors, including TNF-α, IL-6, and IL-1β, by liver cells, resulting in significant damage to the live structure and functions (37, 38). Our findings demonstrated that AA pretreatment efficiently restored damage of the hepatic architecture and reduced TNF-α, IL-6, and IL-1β secretion in mice with L/D-induced FHF.…”

Section: Discussionmentioning

confidence: 89%

“…Our findings demonstrated that AA pretreatment efficiently restored damage of the hepatic architecture and reduced TNF-α, IL-6, and IL-1β secretion in mice with L/D-induced FHF. Recent studies have shown that ROS, such as the superoxide radical

(O_{2}^{-})

, NO, and hydrogen peroxide (H 2 O 2 ), are essential for the development of L/D-induced FHF (38, 39). Moreover, oxidative stress can increase the production of MPO and MDA formation to further result in liver tissue damage (40).…”

Section: Discussionmentioning

confidence: 99%

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Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

Wang

et al. 2017

Front. Immunol.

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Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i.e., H2O2, NO, and O2−), and increasing the glutathione and superoxide dismutase contents. Moreover, AA treatment significantly inhibited mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway activation via the partial induction of programmed cell death 4 (PDCD4) protein expressions, which are involved in inflammatory responses. Furthermore, AA treatment dramatically induced the expression of the glutamate-cysteine ligase modifier subunit, the glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, and NAD (P) H: quinoneoxidoreductase 1 (NQO1), which are largely dependent on activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) through the induction of AMP-activated protein kinase (AMPK) and glycogen synthase kinase-3β (GSK3β) phosphorylation. Accordingly, AA exhibited protective roles against LPS/d-GalN-induced FHF by inhibiting oxidative stress and inflammation. The underlying mechanism may be associated with the inhibition of MAPK and NF-κB activation via the partial induction of PDCD4 and upregulation of Nrf2 in an AMPK/GSK3β pathway activation-dependent manner.

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Section: Discussionmentioning

confidence: 89%

(O_{2}^{-})

Section: Discussionmentioning

confidence: 99%

Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

Wang

et al. 2017

Front. Immunol.

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“…Acute liver failure (ALF) is commonly associated with gram‐negative bacterial endotoxins. Lipopolysaccharide (LPS) is a major structural and toxic component of the outer membranes of gram‐negative bacteria that interfere with or destroy healthy cells . d ‐Galactosamine (D‐GalN) is able to sensitize toxic impacts of LPS on hepatocytes and it promotes the onset of acute liver failure .…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D‐GalN‐induced acute liver injury by inhibiting NF‐κB and activating Nrf2/HO‐1 signaling pathways

Bian

Liu

et al. 2019

J Sci Food Agric

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BACKGROUND In China, Acanthopanax sessiliflorus is a delicious wild vegetable. It is also used to treat inflammation and pain. Chiisanoside (CSS) is the main constituent of the leaf of A. sessiliflorus. Combined use of lipopolysaccharide and d‐galactosamine (LPS/D‐GalN) can induce acute liver failure in human beings, and there are no reports on the protective effect of CSS against LPS/D‐GalN‐induced acute liver injury in mice. RESULTS Chiisanoside pretreatment evidently reduced the activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the changes induced by LPS/D‐GalN, and these histopathological changes induced by LPS/GalN were significantly weakened. Catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) activities increased, and malondialdehyde (MDA) activity decreased after CSS treatment compared with LPS/D‐GalN treatment. Pretreatment with CSS also inhibited the expression levels of inflammatory factors. The administration of CSS prevented the phosphorylated expression of inhibitor kappa B (IκB) kinase, and led to a significant increase in heme oxygenase‐1 (HO‐1) expression and nuclear factor erythroid 2‐related factor2 (Nrf2) nuclear translocation. CONCLUSION The protective effects of CSS are attributed to its antioxidative effect and inflammatory suppression in Nuclear factor kappa beta (NF‐κB) and Nrf2/HO‐1 signaling pathways. Chiisanoside might therefore be a potential ingredient for drug and food development against acute liver injury in the future. © 2018 Society of Chemical Industry

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“…Although the signal transduction pathways of most members of the TLR family are MyD88-dependent, TLR4 possesses MyD88-dependent and independent pathways for signal transduction [23][24][25]. The signal transduction of the MyD88-dependent pathways is primarily intracellular and results in the transfer of NF-κB to the nucleus; this translocation initiates the transcription of inflammatory cytokines such as TNF-α, IL-1β and IL-6 to amplify inflammatory reactions in a cascade manner, inducing vascular injury and ultimately leading to post-operative restenosis.…”

Section: Introductionmentioning

confidence: 99%

Effect of Paclitaxel+Hirudin on the TLR4-MyD88 Signaling Pathway During Inflammatory Activation of Human Coronary Artery Smooth Muscle Cells and Mechanistic Analysis

Li¹,

Wang²,

Xu³

2018

Cell Physiol Biochem

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Background/Aims: Approximately 10%-20% of patients with acute cardiovascular disease who have received coronary intervention suffer restenosis and high inflammation. The stent compound paclitaxel+hirudin was prepared for the treatment of post-intervention restenosis. This study aimed to explore the anti-inflammatory and anti-restenosis mechanisms of paclitaxel+hirudin with regard to the TLR4/MyD88/NF-κB pathway. Methods: Human coronary artery smooth muscle cells (HCASMCs) at 4-6 generations after in vitro culture were used as a model. Lipopolysaccharide (LPS) was used as an inducer to maximally activate the TLR4/MyD88/NF-κB inflammation pathway. After MyD88 knockdown and selective blocking of MyD88 degradation with epoxomicin, the effects of paclitaxel+hirudin stenting on key sites of the TLR4/MyD88/NF-κB pathway were detected using ELISA, Q-PCR, and western blot analysis. Results: LPS at 1 μg/mL for 48 h was the optimal modeling condition for inflammatory activation of HCASMCs. Paclitaxel+hirudin inhibited the levels of key proteins and the gene expression, except for that of the MyD88 gene, of the TLR4-MyD88 pathway. The trend of the effect of paclitaxel+hirudin on the pathway proteins was similar to that of MyD88 knockdown. After epoxomicin intervention, the inhibitory effects of paclitaxel+hirudin on the key genes and proteins of the TLR4-MyD88 pathway were significantly weakened, which even reached pre-intervention levels. Paclitaxel+hirudin affected the MyD88 protein in a dosage-dependent manner. Conclusion: The paclitaxel+hirudin compound promotes MyD88 degradation in the TLR4/MyD88/NF-κB pathway to reduce the activity of TLR4 and NF-κB p65 and to weaken the LPS-initiated inflammatory reactions of IL-1β, IL-6, and TNF-α.

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Neohesperidin dihydrochalcone down-regulates MyD88-dependent and -independent signaling by inhibiting endotoxin-induced trafficking of TLR4 to lipid rafts

Cited by 31 publications

References 49 publications

Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

Hepatoprotective effect of chiisanoside from Acanthopanax sessiliflorus against LPS/D‐GalN‐induced acute liver injury by inhibiting NF‐κB and activating Nrf2/HO‐1 signaling pathways

Effect of Paclitaxel+Hirudin on the TLR4-MyD88 Signaling Pathway During Inflammatory Activation of Human Coronary Artery Smooth Muscle Cells and Mechanistic Analysis

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