scholarly journals Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 477 ◽  
Author(s):  
Baolong Liu ◽  
Yizhu Lu ◽  
Xingyi Chen ◽  
Philma Glora Muthuraj ◽  
Xingzhi Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Therapeutic Potential ◽  
Disease Model ◽  
Protective Role ◽  
Therapeutic Interventions ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Shiitake Mushroom

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.

Targeting heme oxygenase-1 by quercetin ameliorates alcohol-induced acute liver injury via inhibiting NLRP3 inflammasome activation

2018 ◽  
Vol 9 (8) ◽  
pp. 4184-4193 ◽  
Author(s):  
Shu Liu ◽  
Lei Tian ◽  
Guangrui Chai ◽  
Bo Wen ◽  
Bingyuan Wang
Keyword(s):  
Liver Injury ◽  
Heme Oxygenase ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Heme Oxygenase 1 ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

Quercetin can ameliorate alcohol-induced acute liver injury via inducing heme oxygenase-1 and inhibiting NLRP3 inflammasome activation.

scholarly journals Inhibition of oxidative stress and NLRP3 inflammasome by Saikosaponin-d alleviates acute liver injury in carbon tetrachloride-induced hepatitis in mice

2020 ◽  
Vol 34 ◽  
pp. 205873842095059
Author(s):  
Yirong Chen ◽  
Renye Que ◽  
Liubing Lin ◽  
Yanting Shen ◽  
Jinkai Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Mice Model ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

NLRP3 inflammasome activation results in severe liver inflammation and injury. Saikosaponin-d (SSd) possesses anti-inflammatory and hepatoprotective effects. This study aimed to determine the protective effects of SSd on carbon tetrachloride (CCl4)-induced acute liver injury in mice, and whether oxidative stress and NLRP3 inflammasome activation participate in the process. The CCl4 mice model and controls were induced. The mice were treated with SSd at 1, 1.5, or 2.0 mg/kg in a total volume of 100 µl/25 g of body weight. Liver injury was assessed by histopathology. Oxidative stress was determined using mitochondrial superoxide production (MSP), malondialdehyde (MDA) content, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. NLRP3, ASC, and Caspase 1 were determined by real-time PCR and western blot. IL-1β and IL-18 levels were determined by ELISA. Significantly elevated oxidative stress was induced in the liver by CCl4, as demonstrated by histopathology and increases of MDA and MSP levels and decreases of SOD, GPx, and CAT activities (all P < 0.01). SSd significantly decreased the MDA and MSP levels and increased the activities of SOD, GPx, and CAT (all P < 0.05). The mRNA expression of NLRP3, ASC, and Caspase 1, and the protein expression of Caspase 1-p10, NLRP3, ASC, IL-1β, and IL-18 were significantly increased after CCl4 induction (all P < 0.01). These changes were reversed by SSd (all P < 0.05). Suppression of the oxidative stress and NLRP3 inflammasome activation were involved in SSd-alleviated acute liver injury in CCl4-induced hepatitis.

scholarly journals Hydrogen Sulfide Protects against Paraquat-Induced Acute Liver Injury in Rats by Regulating Oxidative Stress, Mitochondrial Function, and Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Zhenning Liu ◽  
Xiaofeng Wang ◽  
Lei Li ◽  
Guigui Wei ◽  
Min Zhao
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Hydrogen Sulfide ◽  
Liver Injury ◽  
Mitochondrial Function ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Nlrp3 Inflammasome Activation

In addition to the lung, the liver is considered another major target for paraquat (PQ) poisoning. Hydrogen sulfide (H2S) has been demonstrated to be effective in the inhibition of oxidative stress and inflammation. The aim of this study was to investigate the protective effect of exogenous H2S against PQ-induced acute liver injury. The acute liver injury model was established by a single intraperitoneal injection of PQ, evidenced by histological alteration and elevated serum aminotransferase levels. Different doses of NaHS were administered intraperitoneally one hour before exposure to PQ. Analysis of the data shows that exogenous H2S attenuated the PQ-induced liver injury and oxidative stress in a dose-dependent manner. H2S significantly suppressed reactive oxygen species (ROS) generation and the elevation of malondialdehyde content while it increased the ratio of GSH/GSSG and levels of antioxidant enzymes including SOD, GSH-Px, HO-1, and NQO-1. When hepatocytes were subjected to PQ-induced oxidative stress, H2S markedly enhanced nuclear translocation of Nrf2 via S-sulfhydration of Keap1 and resulted in the increase in IDH2 activity by regulating S-sulfhydration of SIRT3. In addition, H2S significantly suppressed NLRP3 inflammasome activation and subsequent IL-1β excretion in PQ-induced acute liver injury. Moreover, H2S cannot reverse the decrease in SIRT3 and activation of the NLRP3 inflammasome caused by PQ in Nrf2-knockdown hepatocytes. In summary, H2S attenuated the PQ-induced acute liver injury by enhancing antioxidative capability, regulating mitochondrial function, and suppressing ROS-induced NLRP3 inflammasome activation. The antioxidative effect of H2S in PQ-induced liver injury can at least partly be attributed to the promotion of Nrf2-driven antioxidant enzymes via Keap1 S-sulfhydration and regulation of SIRT3/IDH2 signaling via Nrf2-dependent SIRT3 gene transcription as well as SIRT3 S-sulfhydration. Thus, H2S supplementation can form the basis for a promising novel therapeutic strategy for PQ-induced acute liver injury.

Rhein, An Anthraquinone Drug, Suppresses the NLRP3 Inflammasome and Macrophage Activation in Urate Crystal-Induced Gouty Inflammation

2019 ◽  
Vol 47 (01) ◽  
pp. 135-151 ◽  
Author(s):  
Wan-Chun Chang ◽  
Mu-Tzu Chu ◽  
Chih-Yuan Hsu ◽  
Yeong-Jian Jan Wu ◽  
Jing-Yi Lee ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Gouty Arthritis ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Caspase 1 ◽  
Text Production ◽  
Nlrp3 Inflammasome Activation ◽  
Urate Crystal

Rhein, an anthraquinone drug, is a widely used traditional Chinese medicine. Rhein is a major bioactive metabolite of diacerein which has been approved for treating osteoarthritis with a good safety profile in humans. Gouty arthritis is an inflammatory disease characterized by urate crystal-induced NLRP3 inflammasome activation with up-regulated caspase-1 protease and IL-1[Formula: see text] in macrophages. Inhibition of the NLRP3 inflammasome formation has been considered as a potential therapeutic avenue for treating or preventing many inflammatory diseases. This study aimed to evaluate the anti-inflammatory effects of rhein on gouty arthritis. Rhein within the physiological levels of humans showed no toxicity on the cell viability and differentiation, but significantly decreased the production of IL-1[Formula: see text], TNF-[Formula: see text] and caspase-1 protease in urate crystal-activated macrophages. Compared to medium controls, rhein at the therapeutic concentration (2.5[Formula: see text][Formula: see text]g/mL) effectively inhibited IL-1[Formula: see text] production by 47% ([Formula: see text]). Rhein did not affect the mRNA levels of CASP1, NLRP3 and ASC, but suppressed the protein expression and enzyme activity of caspase-1. Immunofluorescence confocal microscopy further revealed that rhein suppressed the aggregation of ASC speck and inhibited the formation of NLRP3 inflammasome. Rhein of 5[Formula: see text][Formula: see text]g/mL significantly decreased the ASC speck to 36% ([Formula: see text]), and reduced the NLRP3 aggregates to 37.5% ([Formula: see text]). Our data demonstrate that rhein possesses pharmacological activity to suppress caspase-1 protease activity and IL-1[Formula: see text] production by interfering with the formation of NLRP3 multiprotein complex. These results suggest that rhein has therapeutic potential for treating NLRP3 inflammasome-mediated diseases such as gouty arthritis.

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