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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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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. |
format | Online Article Text |
id | pubmed-7439165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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