Shaoyao Decoction Inhibits Inflammation and Improves Intestinal Barrier Function in Mice With Dextran Sulfate Sodium-Induced Colitis.

Honggang Chi,Dan Wang,Xuebao Zheng,Mengting Chen,Fengyan Yu,Jiantao Lin,Shuhua Zhang,Ying Zou,Jun Zhou

doi:10.3389/fphar.2021.524287

Abstract

Shaoyao decoction (SYD), a classical traditional Chinese medicine formula, is effective for the treatment of inflammatory bowel disease (IBD). This study was designed to investigate the therapeutic effects of SYD on IBD and possible mechanisms. Dextran sulfate sodium (DSS, 3.5%) was used to induce colitis in C57BL/6 mice. Disease phenotypes were investigated based on disease activity index (DAI), colon length, and microscopic and macroscopic scores. Additionally, the presence of proinflammatory cytokines, immune cell infiltrates, intestinal cell proliferation, apoptosis, epithelial permeability, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-κB (NF-κB) signaling, as well as the intestinal mucosal barrier function, were investigated. The administration of SYD significantly ameliorated the clinical signs, suppressed the levels of proinflammatory cytokines, and reduced immune cell infiltrates into colonic tissues of DSS-induced colitis model mice. SYD also significantly reduced the DSS-induced activation of STAT3 and NF-κB signaling. Furthermore, SYD promoted epithelial integrity by regulating epithelial cell apoptosis and epithelial permeability. Finally, we demonstrated that SYD protected the intestinal barrier function by significantly regulating the mucus layer genes Muc1, Muc2, Muc4, and Tff3, as well as the epithelial barrier genes Z O -1 and Occludin. Our results indicate that SYD has a protective effect on DSS-induced colitis, which is attributable to its anti-inflammatory activity and intestinal barrier function-enhancing effects. These results provide valuable insights into the pharmacological actions of SYD for the treatment of IBD.

Highlights

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease, is a group of chronic, relapsing, and remitting inflammatory disorders of the gastrointestinal tract characterized by fever, bloody diarrhea, abdominal cramping, and weight loss (Ivanov et al, 2009)
We investigated whether Shaoyao decoction (SYD) could inhibit the activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor- κB (NF-κB) signaling pathways which are known to regulate the transcription of proinflammatory genes (Atreya et al, 2008; Garrett et al, 2010)
We found that the serum level of fluorescein isothiocyanate (FITC)-dextran was significantly higher in DSS-treated mice than in control mice; it was reduced by SYD treatment (Figure 5D)

Summary

Introduction

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease, is a group of chronic, relapsing, and remitting inflammatory disorders of the gastrointestinal tract characterized by fever, bloody diarrhea, abdominal cramping, and weight loss (Ivanov et al, 2009). IBD therapy is directed toward dampening the inflammatory response in the gastrointestinal tract to alleviate symptoms and involves the use of immunomodulators, anti-tumor necrosis factor-alpha (TNF-α) antibodies, 5-aminosalicylic acid agents, and antimicrobials (Baumgart and Sandborn, 2012; Cheifetz et al, 2017). The currently used treatment methods are generally considered effective, not all patients achieve sustained remission and treatment is usually limited by adverse reactions (Quezada et al, 2018). Alternative medicines, such as traditional Chinese medicine formulas and natural food substances, are desirable because of their efficacy and safety

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Conclusion