PMID- 35765026
OWN - NLM
STAT- MEDLINE
DCOM- 20220630
LR  - 20220716
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Jun 28
TI  - Rhubarb free anthraquinones improved mice nonalcoholic fatty liver disease by 
      inhibiting NLRP3 inflammasome.
PG  - 294
LID - 10.1186/s12967-022-03495-4 [doi]
LID - 294
AB  - 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-1beta) 
      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.
CI  - (c) 2022. The Author(s).
FAU - Wu, Chao
AU  - Wu C
AD  - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of 
      Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese 
      Medicine, No.528 Zhangheng Road Pudong New District, Shanghai, 201203, China.
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
FAU - Bian, Yanqin
AU  - Bian Y
AD  - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of 
      Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese 
      Medicine, No.528 Zhangheng Road Pudong New District, Shanghai, 201203, China.
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
AD  - Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese 
      Medicine, Shanghai, China.
FAU - Lu, Bingjie
AU  - Lu B
AD  - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of 
      Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese 
      Medicine, No.528 Zhangheng Road Pudong New District, Shanghai, 201203, China.
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
FAU - Wang, Dan
AU  - Wang D
AD  - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of 
      Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese 
      Medicine, No.528 Zhangheng Road Pudong New District, Shanghai, 201203, China.
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
FAU - Azami, Nisma Lena Bahaji
AU  - Azami NLB
AD  - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of 
      Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese 
      Medicine, No.528 Zhangheng Road Pudong New District, Shanghai, 201203, China.
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
FAU - Wei, Gang
AU  - Wei G
AD  - State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of 
      Genetics and Development, School of Life Sciences, Human Phenome Institute, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Ma, Feng
AU  - Ma F
AD  - Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Suzhou, 215123, People's Republic of China. 
      mafeng_2016@163.com.
FAU - Sun, Mingyu
AU  - Sun M
AUID- ORCID: 0000-0001-8103-7283
AD  - Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of 
      Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese 
      Medicine, No.528 Zhangheng Road Pudong New District, Shanghai, 201203, China. 
      mysun248@hotmail.com.
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 
      mysun248@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220628
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Anthraquinones)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - KA46RNI6HN (Emodin)
SB  - IM
MH  - Animals
MH  - Anthraquinones/pharmacology/therapeutic use
MH  - *Emodin
MH  - Inflammasomes/metabolism
MH  - Inflammation/drug therapy/metabolism
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - *Non-alcoholic Fatty Liver Disease/pathology
MH  - *Rheum/metabolism
PMC - PMC9238089
OTO - NOTNLM
OT  - NAFLD
OT  - NLRP3 inflammasome
OT  - Rhubarb free anthraquinones
COIS- The authors declare no competing financial interests.
EDAT- 2022/06/29 06:00
MHDA- 2022/07/01 06:00
PMCR- 2022/06/28
CRDT- 2022/06/28 23:40
PHST- 2022/04/25 00:00 [received]
PHST- 2022/06/20 00:00 [accepted]
PHST- 2022/06/28 23:40 [entrez]
PHST- 2022/06/29 06:00 [pubmed]
PHST- 2022/07/01 06:00 [medline]
PHST- 2022/06/28 00:00 [pmc-release]
AID - 10.1186/s12967-022-03495-4 [pii]
AID - 3495 [pii]
AID - 10.1186/s12967-022-03495-4 [doi]
PST - epublish
SO  - J Transl Med. 2022 Jun 28;20(1):294. doi: 10.1186/s12967-022-03495-4.