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, Shunyi; Xu, Kangquan; Yang, Hongzhi

doi:10.1155/2020/8786424

Cited by 8 publications

(8 citation statements)

References 81 publications

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“…Clinically, these TCM theories have been extensively used to treat both the heart diseases and liver diseases. For example, the methods of "Shu-Liver, 疏肝" and "Rou-Liver, 柔肝" based on "treating the heart disease from the liver" have been extensively used for treating coronary heart disease [24][25][26], and the methods of "Xing-Qi-Huo-Xue, 行气活血" and "Bu-Xue, 补血" have been used for treating nonalcoholic fatty liver disease (NAFLD) [27][28][29][30]. ese : e disturbance of liver-heart homeostasis in TCM.…”

Section: Liver and Heart In "Five-zang Correlationmentioning

confidence: 99%

“…Heart can modulate the pathophysiology of the liver based on the TCM theory of "illness of the child-organ involving the mother-organ," and liver can influence the pathophysiology of the heart based on the TCM theory of "mother-organ disorder involving its child-organ," respectively ( Figure 1). us, the coronary heart disease can be treated from the liver based on the TCM theory of "treating the heart disease from the liver" [24][25][26], and NAFLD can be treated by the methods of "Xing-Qi-Huo-Xue" and "Bu-Xue" in the clinical practice of TCM [27][28][29][30]. erefore, the evidences from TCM to Modern Medicine, and from basic research studies to clinical investigations, show that there exists interorgan crosstalk between the liver and heart (the heart and liver).…”

Section: Perspectivementioning

confidence: 99%

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Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine

Zhang

Xian-ming

2021

Evidence-Based Complementary and Alternative Medicine

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There is a close relationship between the liver and heart based on “zang-xiang theory,” “five-element theory,” and “five-zang/five-viscus/five-organ correlation theory” in the theoretical system of Traditional Chinese Medicine (TCM). Moreover, with the development of molecular biology, genetics, immunology, and others, the Modern Medicine indicates the existence of the essential interorgan communication between the liver and heart (the heart and liver). Anatomically and physiologically, the liver and heart are connected with each other primarily via “blood circulation.” Pathologically, liver diseases can affect the heart; for example, patients with end-stage liver disease (liver failure/cirrhosis) may develop into “cirrhotic cardiomyopathy,” and nonalcoholic fatty liver disease (NAFLD) may promote the development of cardiovascular diseases via multiple molecular mechanisms. In contrast, heart diseases can affect the liver, heart failure may lead to cardiogenic hypoxic hepatitis and cardiac cirrhosis, and atrial fibrillation (AF) markedly alters the hepatic gene expression profile and induces AF-related hypercoagulation. The heart can also influence liver metabolism via certain nonsecretory cardiac gene-mediated multiple signals. Moreover, organokines are essential mediators of organ crosstalk, e.g., cardiomyokines link the heart to the liver, while hepatokines link the liver to the heart. Therefore, both TCM and Western Medicine, and both the basic research studies and the clinical practices, all indicate that there exist essential “heart-liver axes” and “liver-heart axes.” To investigate the organ interactions between the liver and heart (the heart and liver) will help us broaden and deepen our understanding of the pathogenesis of both liver and heart diseases, thus improving the strategies of prevention and treatment in the future.

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Section: Liver and Heart In "Five-zang Correlationmentioning

confidence: 99%

Section: Perspectivementioning

confidence: 99%

Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine

Zhang

Xian-ming

2021

Evidence-Based Complementary and Alternative Medicine

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“…Given that NAFLD is accompanied by obesity, and considering that the known impacts of TLR4 signaling in high-fat-induced metabolic disarrangements ( Liu et al., 2019 ; Zhang et al., 2020b ), we therefore examined obesity-related parameters in HFD-fed mice in the presence of CLI-095 treatment. Sin A treatment significantly inhibited body weight gain in NAFLD mice, whereas CLI-095 administration abolished this improvement ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

Schisantherin A alleviates non-alcoholic fatty liver disease by restoring intestinal barrier function

Jiang

Li³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is intricately linked to dysregulation of the gut–liver axis, and correlated with intestinal inflammation and barrier disruption.ObjectivesTo investigate the protective effects and possible molecular mechanism of Schisantherin A (Sin A) in a high-fat diet (HFD) induced NAFLD mouse model.MethodsHFD-fed NAFLD mice were treated with the vehicle and 80 mg/kg Sin A every day for 6 weeks. The gut permeability of the NAFLD mice was assessed by intestinal permeability assays in vivo and transepithelial electrical resistance (TEER) measurements in vitro were also used to evaluate the function of the gut barrier. TLR4 inhibitor was then used to investigate the impact of Sin A in the LPS- TLR4 signaling pathway. Alternatively, the composition of the microbiome was assessed using 16S rRNA amplification. Finally, the experiment of antibiotic treatment was performed to elucidate the roles of the gut microbiome mediating Sin A induced metabolic benefits in the NAFLD mice.ResultsWe found that Sin A potently ameliorated HFD-induced hepatic steatosis and inflammation, alleviated gut inflammation, and restored intestinal barrier function. We also observed that Sin A improved gut permeability and reduced the release of lipopolysaccharide (LPS) into circulation and further found that Sin A can suppress LPS-TLR4 signaling to protect against HFD-induced NAFLD. Sin A treatment altered the composition of the microbiome in NAFLD mice compared to vehicle controls.ConclusionsSin A is an effective and safe hepatoprotective agent against HFD-induced NAFLD by partly ameliorating gut inflammation, restoring intestinal barrier function, and regulating intestinal microbiota composition.

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“…SWT, a TCM formula used in clinical practice to treat menstrual discomfort and infertility for centuries, has recently been investigated for its therapeutic effects on chronic liver diseases [ 22 ]. However, the underlying mechanisms of SWT against fibrotic liver injury remain to be further elucidated.…”

Section: Discussionmentioning

confidence: 99%

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

Xue

Ding

et al. 2021

Chin Med

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Background Fibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury. Methods UHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson’s trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC–MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot. Results SWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways. Conclusion SWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.

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

Cited by 8 publications

References 81 publications

Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine

Hepatocardiac or Cardiohepatic Interaction: From Traditional Chinese Medicine to Western Medicine

Schisantherin A alleviates non-alcoholic fatty liver disease by restoring intestinal barrier function

Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis

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