Abstract

Ulcerative colitis (UC) is a chronic intestinal disease with unclear pathogenesis. With an increasing global prevalence over the past two decades, UC poses a serious threat to public health. Baitouweng decoction (BTW), a traditional Chinese medicine, has been shown to have good clinical efficacy for treating intestinal inflammation. Yet, the efficacy of BTW in UC and the underlying mechanism remain unclear. The current study aimed to determine whether BTW suppressed intestinal inflammation in mice and the potential mechanism. We used a dextran sulfate sodium (DSS)-induced murine colitis model to test the anti-inflammatory efficacy of BTW. Clinical symptoms were scored by the disease activity index (DAI), and the colon length and pathological changes in colon tissue were also used to further evaluate the efficacy of BTW. Precisely how BTW affected immune function and the intestinal barrier of UC mice was also examined. BTW significantly reduced DAI score and colonic pathological damage. BTW regulated the balance between T helper (Th)17 and regulatory T (Treg) cells, decreased interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, and increased IL-10 levels. BTW reduced intestinal permeability of UC mice, increased expression of tight junction proteins (occludin and zonula occludens-1), and decreased expression of phospho-nuclear factor (p-NF)-κB and phospho-extracellular signal-regulated kinase (p-ERK) in the colon. BTW inhibited the ERK/p-NF-κB signaling pathway and suppressed expression of cyclo-oxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW 264.7 cells. BTW significantly promoted the synthesis of short-chain fatty acids in the gut, particularly acetate, propionate, isobutyric acid, and isovalerate. The results suggest that BTW can protect against DSS-induced UC. The mechanism may be partially attributed to regulating the balance of Th17/Treg cells and restoring the intestinal epithelial barrier.

Highlights

  • Ulcerative colitis (UC) is a state of chronic, recurrent intestinal inflammation presenting with abdominal pain, diarrhea, and mucopurulent stools as the key symptoms

  • An in-house component library of Baitouweng decoction (BTW) and MS1 and MS and tandem MS (MS/MS) data was compared to the literature or standards

  • The literature shows a balance of Th17 and Treg cell functions in the development of colitis

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Summary

INTRODUCTION

Ulcerative colitis (UC) is a state of chronic, recurrent intestinal inflammation presenting with abdominal pain, diarrhea, and mucopurulent stools as the key symptoms. Baitouweng decoction (BTW), a well-known TCM prescription, has a documented history of >2000 years. It is widely used and is effective against various types of enteritis. BTW is composed of four TCMs: Pulsatilla chinensis (Bunge) Regel (Baitouweng), Coptis chinensis Franch (Huanglian), Phellodendron chinense C. Previous studies have indicated that the extract of Pulsatilla chinensis (Bunge) Regel acts as an anti-inflammatory and immunomodulator in a mouse model of lipopolysaccharide (LPS)-induced systemic inflammation (Kang et al, 2019). Coptidine and berberine, which are the main components in Coptis chinensis Franch, have been shown to exert antitumor, anti-inflammatory, and antibacterial effects in rats (Wu J. et al, 2019; Zhu et al, 2019). The current study investigated the mechanism by which BTW successfully suppressed gut inflammation in mice with dextran sulfate sodium (DSS)-induced UC

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