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

Yaxing Zhang; Ge Zhou; Zifeng Chen; Weibing Guan; Jiongshan Zhang; Mingmin Bi; Fenglin Wang; Xinchao You; Yangjing Liao; Shuhui Zheng; Kangquan Xu; Hongzhi Yang

doi:10.1155/2020/8786424

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

Evid Based Complement Alternat Med. 2020 Aug 11:2020:8786424. doi: 10.1155/2020/8786424. eCollection 2020.

Authors

Yaxing Zhang^{1

2}, Ge Zhou^{1

2}, Zifeng Chen^{3

4}, Weibing Guan^{1

2}, Jiongshan Zhang^{1

2}, Mingmin Bi^{5

6}, Fenglin Wang^{1

2}, Xinchao You⁷, Yangjing Liao^{1

2}, Shuhui Zheng⁸, Kangquan Xu^{3

4}, Hongzhi Yang^{1

2}

Affiliations

¹ Department of Traditional Chinese Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Institute of Integrated Traditional Chinese and Western Medicine, Sun Yat-sen University, Guangzhou, China.
³ Biofeedback Laboratory, Xinhua College of Sun Yat-sen University, Guangzhou, China.
⁴ School of Biomedical Engineering, Xinhua College of Sun Yat-sen University, Guangzhou, China.
⁵ Department of Otorhinolaryngology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁶ Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
⁷ Department of Science and Education, The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China.
⁸ Research Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

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.