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Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has high global prevalence; however, the treatments of NAFLD are limited due to lack of approved drugs. METHODS: Mice were randomly assigned into three groups: Control group, NAFLD group, NAFLD plus Si-Wu-Tang group. A NAFLD mice model was establi...

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Autores principales: Zhang, Yaxing, Zhou, Ge, Chen, Zifeng, Guan, Weibing, Zhang, Jiongshan, Bi, Mingmin, Wang, Fenglin, You, Xinchao, Liao, Yangjing, Zheng, Shuhui, Xu, Kangquan, Yang, Hongzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439165/
https://www.ncbi.nlm.nih.gov/pubmed/32849904
http://dx.doi.org/10.1155/2020/8786424
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author Zhang, Yaxing
Zhou, Ge
Chen, Zifeng
Guan, Weibing
Zhang, Jiongshan
Bi, Mingmin
Wang, Fenglin
You, Xinchao
Liao, Yangjing
Zheng, Shuhui
Xu, Kangquan
Yang, Hongzhi
author_facet Zhang, Yaxing
Zhou, Ge
Chen, Zifeng
Guan, Weibing
Zhang, Jiongshan
Bi, Mingmin
Wang, Fenglin
You, Xinchao
Liao, Yangjing
Zheng, Shuhui
Xu, Kangquan
Yang, Hongzhi
author_sort Zhang, Yaxing
collection PubMed
description BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has high global prevalence; however, the treatments of NAFLD are limited due to lack of approved drugs. METHODS: Mice were randomly assigned into three groups: Control group, NAFLD group, NAFLD plus Si-Wu-Tang group. A NAFLD mice model was established by feeding with a methionine- and choline-deficient (MCD) diet for four weeks. Si-Wu-Tang was given orally by gastric gavage at the beginning of 3rd week, and it lasted for two weeks. The treatment effects of Si-Wu-Tang were confirmed by examining the change of body weight, serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, Oil Red O staining, and hematoxylin and eosin (H&E) staining of the liver samples and accompanied by steatosis grade scores. The expression and activation of the possible signaling proteins involved in the pathogenesis of NAFLD were determined by western blotting. RESULTS: Mice fed with four weeks of MCD diet displayed elevated serum levels of ALT and AST, while there was decreased body weight. The hepatic Oil Red O staining and H&E staining showed severe liver steatosis with high steatosis grade scores. All these can be improved by treating with Si-Wu-Tang for two weeks. Mechanistically, the increased hepatic TLR4 expression and its downstream JNK phosphorylation induced by MCD diet were suppressed by Si-Wu-Tang. Moreover, the upregulations of Caspase-8, gasdermin D (GSDMD), and cleaved-GSDMD in liver mediated by MCD diet were all inhibited by Si-Wu-Tang. CONCLUSIONS: Treatment with Si-Wu-Tang improves MCD diet-induced NAFLD in part via blocking TLR4-JNK and Caspase-8-GSDMD signaling pathways, suggesting that Si-Wu-Tang has potential for clinical application in treating NAFLD.
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spelling pubmed-74391652020-08-25 Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways Zhang, Yaxing Zhou, Ge Chen, Zifeng Guan, Weibing Zhang, Jiongshan Bi, Mingmin Wang, Fenglin You, Xinchao Liao, Yangjing Zheng, Shuhui Xu, Kangquan Yang, Hongzhi Evid Based Complement Alternat Med Research Article BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has high global prevalence; however, the treatments of NAFLD are limited due to lack of approved drugs. METHODS: Mice were randomly assigned into three groups: Control group, NAFLD group, NAFLD plus Si-Wu-Tang group. A NAFLD mice model was established by feeding with a methionine- and choline-deficient (MCD) diet for four weeks. Si-Wu-Tang was given orally by gastric gavage at the beginning of 3rd week, and it lasted for two weeks. The treatment effects of Si-Wu-Tang were confirmed by examining the change of body weight, serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, Oil Red O staining, and hematoxylin and eosin (H&E) staining of the liver samples and accompanied by steatosis grade scores. The expression and activation of the possible signaling proteins involved in the pathogenesis of NAFLD were determined by western blotting. RESULTS: Mice fed with four weeks of MCD diet displayed elevated serum levels of ALT and AST, while there was decreased body weight. The hepatic Oil Red O staining and H&E staining showed severe liver steatosis with high steatosis grade scores. All these can be improved by treating with Si-Wu-Tang for two weeks. Mechanistically, the increased hepatic TLR4 expression and its downstream JNK phosphorylation induced by MCD diet were suppressed by Si-Wu-Tang. Moreover, the upregulations of Caspase-8, gasdermin D (GSDMD), and cleaved-GSDMD in liver mediated by MCD diet were all inhibited by Si-Wu-Tang. CONCLUSIONS: Treatment with Si-Wu-Tang improves MCD diet-induced NAFLD in part via blocking TLR4-JNK and Caspase-8-GSDMD signaling pathways, suggesting that Si-Wu-Tang has potential for clinical application in treating NAFLD. Hindawi 2020-08-11 /pmc/articles/PMC7439165/ /pubmed/32849904 http://dx.doi.org/10.1155/2020/8786424 Text en Copyright © 2020 Yaxing Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Yaxing
Zhou, Ge
Chen, Zifeng
Guan, Weibing
Zhang, Jiongshan
Bi, Mingmin
Wang, Fenglin
You, Xinchao
Liao, Yangjing
Zheng, Shuhui
Xu, Kangquan
Yang, Hongzhi
Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways
title Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways
title_full Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways
title_fullStr Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways
title_full_unstemmed Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways
title_short Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways
title_sort si-wu-tang alleviates nonalcoholic fatty liver disease via blocking tlr4-jnk and caspase-8-gsdmd signaling pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439165/
https://www.ncbi.nlm.nih.gov/pubmed/32849904
http://dx.doi.org/10.1155/2020/8786424
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