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Nonalcoholic fatty liver disease (NAFLD) has high global prevalence; however, the treatments of NAFLD are limited due to lack of approved drugs. <jats:italic>Methods<\/jats:italic>. Mice were randomly assigned into three groups: Control group, NAFLD group, NAFLD plus Si\u2010Wu\u2010Tang group. A NAFLD mice model was established by feeding with a methionine\u2010 and choline\u2010deficient (MCD) diet for four weeks. Si\u2010Wu\u2010Tang was given orally by gastric gavage at the beginning of 3rd week, and it lasted for two weeks. The treatment effects of Si\u2010Wu\u2010Tang 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&amp;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. <jats:italic>Results<\/jats:italic>. 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&amp;E staining showed severe liver steatosis with high steatosis grade scores. All these can be improved by treating with Si\u2010Wu\u2010Tang for two weeks. Mechanistically, the increased hepatic TLR4 expression and its downstream JNK phosphorylation induced by MCD diet were suppressed by Si\u2010Wu\u2010Tang. Moreover, the upregulations of Caspase\u20108, gasdermin D (GSDMD), and cleaved\u2010GSDMD in liver mediated by MCD diet were all inhibited by Si\u2010Wu\u2010Tang. <jats:italic>Conclusions<\/jats:italic>. Treatment with Si\u2010Wu\u2010Tang improves MCD diet\u2010induced NAFLD in part via blocking TLR4\u2010JNK and Caspase\u20108\u2010GSDMD signaling pathways, suggesting that Si\u2010Wu\u2010Tang has potential for clinical application in treating NAFLD.<\/jats:p>","DOI":"10.1155\/2020\/8786424","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:07Z","timestamp":1597190407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Si\u2010Wu\u2010Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4\u2010JNK and Caspase\u20108\u2010GSDMD Signaling Pathways"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1179-8076","authenticated-orcid":false,"given":"Yaxing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibing","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiongshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingmin","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchao","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangjing","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangquan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-1931","authenticated-orcid":false,"given":"Hongzhi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2019.08.006"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29367"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0212-0"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.003"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30702"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6491420"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i30.6890"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-012-0993-2"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-012-1836-0"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-016-0102-0"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-8"},{"key":"e_1_2_10_14_2","first-page":"175","article-title":"Serum fructose concentration in rats after single dose oral administration of Si-Wu-Tang","volume":"4","author":"Liang Q. 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