Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and NLRP3 Inflammasome

Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. Administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) triggers acute liver injury in mice, simulating many clinical features of FHF in humans; therefore, this disease model is often used to investigate potential therapeutic interventions to treat FHF. Recently, suppression of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, was shown to alleviate the severity of GalN/LPS-induced liver damage in mice. Therefore, the goal of this study was to find dietary exosome-like nanoparticles (ELNs) with therapeutic potential in curbing FHF by suppressing the NLRP3 inflammasome. Seven commonly consumed mushrooms were used to extract ELNs. These mushrooms were found to contain ELNs composed of RNAs, proteins, and lipids. Among these mushroom-derived ELNs, only shiitake mushroom-derived ELNs (S-ELNs) substantially inhibited NLRP3 inflammasome activation by preventing inflammasome formation in primary macrophages. S-ELNs also suppressed the secretion of interleukin (IL)-6, as well as both protein and mRNA levels of the Il1b gene. Remarkably, pre-treatment with S-ELNs protected mice from GalN/LPS-induced acute liver injury. Therefore, S-ELNs, identified as potent new inhibitors of the NLRP3 inflammasome, represent a promising class of agents with the potential to combat FHF.

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Mitophagy protects against acetaminophen-induced acute liver injury in mice through inhibiting NLRP3 inflammasome activation

Biochemical Pharmacology ◽

10.1016/j.bcp.2019.113643 ◽

2019 ◽

Vol 169 ◽

pp. 113643 ◽

Cited By ~ 12

Author(s):

Shulin Shan ◽

Zhenyu Shen ◽

Cuiqin Zhang ◽

Ruirui Kou ◽

Keqin Xie ◽

...

Keyword(s):

Liver Injury ◽

Nlrp3 Inflammasome ◽

Acute Liver Injury ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation

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Identification of Exosome-Like Nanoparticles as a New Bioactive Component in Honey

Current Developments in Nutrition ◽

10.1093/cdn/nzab037_093 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 383-383

Author(s):

Jiujiu Yu

Keyword(s):

Liver Injury ◽

Nlrp3 Inflammasome ◽

Acute Liver Injury ◽

Medical Science ◽

The United States ◽

United States Department ◽

Bioactive Component ◽

Medicinal Food ◽

Anti Inflammatory ◽

Experimentally Induced

Abstract Objectives To investigate whether honey, as a medicinal food, contain exosome-like nanoparticles (ELNs). Methods Honey was diluted in phosphate-buffered saline and subjected to sequential centrifugation followed by ultracentrifugation. ELNs were obtained from honey. Such ELNs were characterized in detail by electron microscopy analysis and biomolecule omics analysis. The anti-inflammatory functions of these honey-derived ELNs (H-ELNs) were studied in primary macrophages and experimentally induced acute liver injury in mice. Results H-ELNs were membrane-enclosed nanoparticles composed of lipids, proteins, and RNAs. These nanoparticles specifically hindered assembly and activation of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, which is a critical pro-inflammatory enzyme complex in the innate immune system. H-ELNs protected mice from acute inflammation and liver damage in the experimentally induced acute liver injury. microRNA miR-4057 in H-ELNs was found to potently inhibit activation of the NLRP3 inflammasome. Conclusions H-ELNs were identified as a new bioactive component in honey and these nanoparticles demonstrated potent anti-inflammatory function in vitro and in vivo. This finding opens a new avenue for studying honey, a medicinal food since ancient times. Funding Sources This work was supported by the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) and the National Institutes of Health (NIH) National Institute for General Medical Science (NIGMS).

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HYPERGLYCEMIA AGGRAVATES ACUTE LIVER INJURY BY PROMOTING LIVER-RESIDENT MACROPHAGE NLRP3 INFLAMMASOME ACTIVATION VIA THE INHIBITION OF AMPK/MTOR-MEDIATED AUTOPHAGY INDUCTION

Transplantation Journal ◽

10.1097/01.tp.0000701340.80509.6e ◽

2020 ◽

Vol 104 (S3) ◽

pp. S526-S526

Author(s):

Wang Qi ◽

Wei Song ◽

Zhou Haoming ◽

Lu Ling

Keyword(s):

Liver Injury ◽

Nlrp3 Inflammasome ◽

Acute Liver Injury ◽

Inflammasome Activation ◽

Resident Macrophage ◽

Nlrp3 Inflammasome Activation ◽

Autophagy Induction

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Oleoylethanolamide Protects Against Acute Liver Injury by Regulating Nrf-2/HO-1 and NLRP3 Pathways in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2020.605065 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiaji Hu ◽

Zhoujie Zhu ◽

Hanglu Ying ◽

Jie Yao ◽

Huabin Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Nlrp3 Inflammasome ◽

Acute Liver Injury ◽

Inflammatory Factors ◽

High Morbidity ◽

Therapeutic Effects ◽

Protective Effects ◽

Mechanism Study ◽

Oxidation Activity

Acute liver injury is a rapidly deteriorating clinical condition with markedly high morbidity and mortality. Oleoylethanolamide (OEA) is an endogenous lipid messenger with multiple bioactivities, and has therapeutic effects on various liver diseases. However, effects of OEA on acute liver injury remains unknown. In this study, effects and mechanisms of OEA in lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced acute liver injury in mice were investigated. We found that OEA treatment significantly attenuated LPS/D-Gal-induced hepatocytes damage, reduced liver index (liver weight/body weight), decreased plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels. Moreover, mechanism study suggested that OEA pretreatment significantly reduced hepatic MDA levels, increased Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) activities via up-regulate Nrf-2 and HO-1 expression to exert anti-oxidation activity. Additionally, OEA markedly reduced the expression levels of Bax, Bcl-2 and cleaved caspase-3 to suppress hepatocyte apoptosis. Meanwhile, OEA remarkedly reduced the number of activated intrahepatic macrophages, and alleviated the mRNA expression of pro-inflammatory factors, including TNF-α, IL-6, MCP1 and RANTES. Furthermore, OEA obviously reduced the expression of IL-1β in liver and plasma through inhibit protein levels of NLRP3 and caspase-1, which indicated that OEA could suppress NLRP3 inflammasome pathway. We further determined the protein expression of PPAR-α in liver and found that OEA significantly increase hepatic PPAR-α expression. In addition, HO-1 inhibitor ZnPP blocked the therapeutic effects of OEA on LPS/D-Gal-induced liver damage and oxidative stress, suggesting crucial role of Nrf-2/HO-1 pathway in the protective effects of OEA in acute liver injury. Together, these findings demonstrated that OEA protect against the LPS/D-Gal-induced acute liver injury in mice through the inhibition of apoptosis, oxidative stress and inflammation, and its mechanisms might be associated with the Nrf-2/HO-1 and NLRP3 inflammasome signaling pathways.

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