Rhubarb free anthraquinones improved mice nonalcoholic fatty liver disease by inhibiting NLRP3 inflammasome

Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and has become a huge public health issue worldwide. Inhibition of nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a potential therapeutic strategy...

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Bibliographic Details
Published in:Journal of translational medicine 2022-06, Vol.20 (1), p.1-294, Article 294
Main Authors: Wu, Chao, Bian, Yanqin, Lu, Bingjie, Wang, Dan, Azami, Nisma Lena Bahaji, Wei, Gang, Ma, Feng, Sun, Mingyu
Format: Article
Language:English
Subjects:
Anthraquinones
Antibodies
Apoptosis
Arthritis
Bone marrow
Care and treatment
Caspase-1
Cell culture
Cholesterol
Clinical trials
Drug delivery
Drugs
Emodin
Experiments
Fatty liver
Fibrosis
Health aspects
Hepatocytes
IL-1β
Inflammasomes
Inflammation
Interleukin 1
Lipopolysaccharides
Liver cancer
Liver diseases
Macrophages
Methionine
Mortality
NAFLD
NLRP3
NLRP3 inflammasome
Nutrient deficiency
Oligomerization
Osteoarthritis
Physiological aspects
Public health
Pyrin protein
Rhubarb free anthraquinones
Testing
Tumor necrosis factor-α
Veins & arteries
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Summary:Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and has become a huge public health issue worldwide. Inhibition of nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome is a potential therapeutic strategy for NAFLD. Currently, there are no drugs targeting NLRP3 inflammasome for clinical treatment of NAFLD. In this study, we explored the efficacy and mechanism of rhubarb free anthraquinones (RFAs) in treating NAFLD by inhibiting NLRP3 inflammasome. Methods First, NLRP3 inflammasome was established in mouse bone marrow-derived macrophages (BMDMs), Kuffer cells and primary hepatocytes stimulated by lipopolysaccharide (LPS) and inflammasome inducers to evaluate the effect of RFAs on inhibiting NLRP3 inflammasome and explore the possible mechanism. Further, Mice NAFLD were established by methionine and choline deficiency diet (MCD) to verify the effect of RFAs on ameliorating NAFLD by inhibiting NLRP3 inflammasome. Results Our results demonstrated that RFAs including rhein/diacerein, emodin, aloe emodin and 1,8-dihydroxyanthraquinone inhibited interleukin-1 beta (IL-1[beta]) but had no effect on tumor necrosis factor-alpha (TNF-[alpha]). Similar results were also showed in mouse primary hepatocytes and Kuffer cells. RFAs inhibited cleavage of caspase-1, formation of apoptosis-associated speck-like protein containing a CARD (ASC) speck, and the combination between NLRP3 and ASC. Moreover, RFAs improved liver function, serum inflammation, histopathological inflammation score and liver fibrosis. Conclusions RFAs including rhein/diacerein, emodin, aloe emodin and 1,8-dihydroxyanthraquinone ameliorated NAFLD by inhibiting NLRP3 inflammasome. RFAs might be a potential therapeutic agent for NAFLD. Graphical Keywords: Rhubarb free anthraquinones, NAFLD, NLRP3 inflammasome
ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-022-03495-4