Benzyl isothiocyanate ameliorates high-fat/cholesterol/cholic acid diet-induced nonalcoholic steatohepatitis through inhibiting cholesterol crystal-activated NLRP3 inflammasome in Kupffer cells

2020 ◽  
Vol 393 ◽  
pp. 114941 ◽  
Author(s):  
Haw-Wen Chen ◽  
Chih-Ching Yen ◽  
Li-Li Kuo ◽  
Chia-Wen Lo ◽  
Chin-Shiu Huang ◽  
...  
Keyword(s):  
Cholic Acid ◽  
Kupffer Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Nlrp3 Inflammasome ◽  
Cholesterol Crystal ◽  
High Fat ◽  
Benzyl Isothiocyanate ◽  
Acid Diet

scholarly journals Benzyl Isothiocyanate Reduces High-Fat/High-Cholesterol/Cholic Acid Diet-Induced Non-Alcoholic Steatohepatitis by Inhibiting the Activation of NLRP3 Inflammasome (P06-084-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Li-Li Ko ◽  
Haw-wen Chen ◽  
Chong-Kuei Lii
Keyword(s):  
Total Cholesterol ◽  
Cholic Acid ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
High Cholesterol ◽  
High Fat ◽  
Benzyl Isothiocyanate ◽  
Alcoholic Steatohepatitis ◽  
Caspase 1 ◽  
Acid Diet

Abstract Objectives Non-alcoholic steatohepatitis (NASH) is one kind of fatty liver disease, which is associated with obesity. Benzyl isothiocyanate (BITC), an organosulfur compound enriched in cruciferous vegetables, shows anti-inflammatory, antioxidant, and anti-tumor activities. This study examined whether BITC protects against high-fat/high-cholesterol/cholic acid diet-induced NASH and the underlying mechanisms involved. Methods Male C57BL/6 J mice were randomly assigned into three groups: normal diet (ND), high-fat/high-cholesterol/cholic acid diet (HFCCD), or HFCCD supplemented with 0.1% BITC. After a 9-weeks feeding, liver tissues and blood samples were collected for analysis. Results Compared with mice fed with ND, the liver weight and the contents of serum GOP, GPT, and total cholesterol as well as hepatic triglycerides and total cholesterol were significantly increased in mice fed with HFCCD (p < 0.05). HFCCD-induced increases in serum GPT and hepatic triglyceride were significantly decreased by BITC (p < 0.05). Histological examination revealed that macrophage infiltration, fibrosis, and the formation of crown-like structure were induced in mice fed with HFCCD, and these inductions were attenuated by BITC. Increases in the expression of NLRP3 mRNA and protein and caspase 1 and IL-1β mRNA as well as the cleaved caspase 1 (p20) and IL-1β (p17) proteins in the liver as well as serum IL-1β concentration were evidenced in HFCCD-fed mice. In the presence of BITC, HFCCD-induced hepatic NLRP3, caspase 1, and IL-1β expression was mitigated. Conclusions These findings suggest that BITC possesses potent anti-steatohepatitis activity, and this protection is likely to be associated with the inhibition of NLRP3 inflammasome activation. Funding Sources This study was supported by the Minister of Science and Technology, Taiwan.

scholarly journals Deficiency of the Purinergic Receptor 2X7 Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Claudia Blasetti Fantauzzi ◽  
Stefano Menini ◽  
Carla Iacobini ◽  
Chiara Rossi ◽  
Eleonora Santini ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Purinergic Receptor ◽  
High Fat ◽  
Liver Sinusoidal Endothelial Cells ◽  
Nonalcoholic Fatty Liver ◽  
Markers Of Inflammation

Molecular mechanisms driving transition from simple steatosis to nonalcoholic steatohepatitis (NASH), a critical step in the progression of nonalcoholic fatty liver disease (NAFLD) to cirrhosis, are poorly defined. This study aimed at investigating the role of the purinergic receptor 2X7 (PR2X7), through the NLRP3 inflammasome, in the development of NASH. To this end, mice knockout for the Pr2x7 gene (Pr2x7−/−) and coeval wild-type (WT) mice were fed a high-fat diet (HFD) or normal-fat diet for 16 weeks. NAFLD grade and stage were lower in Pr2x7−/− than WT mice, and only 1/7 Pr2x7−/− animals showed evidence of NASH, as compared with 4/7 WT mice. Molecular markers of inflammation, oxidative stress, and fibrosis were markedly increased in WT-HFD mice, whereas no or significantly reduced increments were detected in Pr2x7−/− animals, which showed also decreased modulation of genes of lipid metabolism. Deletion of Pr2x7 gene was associated with blunted or abolished activation of NLRP3 inflammasome and expression of its components, which were induced in liver sinusoidal endothelial cells challenged with appropriate stimuli. These data show that Pr2x7 gene deletion protects mice from HFD-induced NASH, possibly through blunted activation of NLRP3 inflammasome, suggesting that PR2X7 and NLRP3 may represent novel therapeutic targets.

Freshwater clam extract reduces liver injury by lowering cholesterol accumulation, improving dysregulated cholesterol synthesis and alleviating inflammation in high-fat, high-cholesterol and cholic acid diet-induced steatohepatitis in mice

2018 ◽  
Vol 9 (9) ◽  
pp. 4876-4887 ◽  
Author(s):  
Hsien-Tsung Yao ◽  
Pei-Feng Lee ◽  
Chong-Kuei Lii ◽  
Yun-Ta Liu ◽  
Szu-Han Chen
Keyword(s):  
Liver Injury ◽  
Cholic Acid ◽  
Cholesterol Synthesis ◽  
Corbicula Fluminea ◽  
High Cholesterol ◽  
High Fat ◽  
Cholesterol Accumulation ◽  
Freshwater Clam ◽  
Acid Diet ◽  
Protective Food

Freshwater clam (Corbicula fluminea) is a traditional liver-protective food in Asia.

scholarly journals Effects of Soothing Liver and Invigorating Spleen Recipes on the IKKβ-NF-κB Signaling Pathway in Kupffer Cells of Nonalcoholic Steatohepatitis Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Xiang-Wen Gong ◽  
Yong-Jian Xu ◽  
Qin-He Yang ◽  
Yin-Ji Liang ◽  
Yu-Pei Zhang ◽  
...  
Keyword(s):  
Liver Function ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Kupffer Cells ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Liver Tissue ◽  
Male Rats ◽  
High Fat ◽  
Mrna And Protein Expression

This study investigates the effect of soothing liver and invigorating spleen recipes on steatohepatitis examining the IKKβ-NF-κB signaling pathway in KCs of NASH rats. SD male rats were randomly divided into 8 groups, and the NASH model was induced by a high-fat diet (HFD). After 26 weeks, liver tissue was examined in H&E stained sections and liver function was monitored biochemically. KCs were isolated by Seglen’s method, with some modifications. The mRNA and protein expression of the IKKβ-NF-κB signaling pathway components was examined by quantitative PCR and Western blotting. The results show that the high-fat diet induced NASH in the rats, and the soothing liver recipe and invigorating spleen recipe decreased the levels of TNF-α, IL-1, and IL-6 in KCs, as well as inhibiting the mRNA and protein expression of the IKKβ-NF-κB signaling pathway components. In conclusion, the experiment indicated the importance of the IKKβ-NF-κB signaling pathway in KCs for the anti-inflammatory effects of the soothing liver and invigorating spleen recipes.

scholarly journals Effects of 12 Weeks of Exercise on Hepatic TNF-α and PPARα in an Animal Model of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

2009 ◽  
Vol 7 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Haifeng Zhang ◽  
Yuxiu He ◽  
Pak Kwong Chung ◽  
Tom K. Tong ◽  
Frank H. Fu ◽  
...  
Keyword(s):  
Animal Model ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
High Fat ◽  
Tnf Α
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