Biochemical and Biophysical Research Communications
Sauchinone ameliorates intestinal inflammation and promotes Th17 cell production of IL-10 via Blimp-1
Introduction
Inflammatory bowel disease (IBD), which mainly consists of Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, unpredictable relapsing inflammatory disease of the gastrointestinal tract. Although the precise etiology and pathophysiology remain unclear, mainstream opinions regard IBD as a complex process with multiple factors involved, including genetic susceptibility, environmental factors, infectious agents, changes in the intestinal flora and dysregulated mucosal immune responses [1]. The prevalence of IBD has shown a steadily increasing trend worldwide, and it is intimately associated with an accumulating cost on society and public health care systems [2]. Therefore, numerous animal and human studies have been performed to determine the pathogenesis of IBD and develop suitable and effective therapeutic strategies.
The conventional therapeutic strategies for IBD include methotrexate, 5-aminosalicylic acid, sulfasalazine, corticosteroids, immunosuppressants and biological agents (i.e., infliximab and vedolizumab). Moreover, some novel drugs have recently emerged. Several small molecule drugs that target different immune signaling pathways are currently enrolled in phase II and III randomized trials, including janus kinase (JAK) inhibitors (tofacitinib) and S1P1 and S1P5 receptor agonists (ozanimod) [3]. However, these therapies for IBD either have limited efficacy or important safety issues, and some patients do not respond well to them in long-term treatment due to a loss of initial response or drug resistance, such as the induction of antibodies against these drugs.
In addition to the therapy strategies mentioned above, accumulating evidence indicates a potential role for medicinal plants in the treatment of IBD based on their validity and security. Numerous plant ingredients have been documented to exhibit anti-inflammatory effects. For example, apple peel polyphenols were found to be noticeable antioxidants that exert anti-inflammatory functions in the gut by inhibiting pro-inflammatory cytokine production and inducing the production of cytoprotective proteins, which could be used in patients with IBD [4]. Anthocyanins, another plant ingredient, were pointed out to exhibit IBD protective effects by regulating various signaling pathways, such as the NF-κB/pERK/MAPK, JAK/STAT signaling, and AMPK pathways [5]. Sauchinone (SAU), a key bioactive lignin isolated from the roots of the herb Saururus chinensis, has acquired more and more attention due to its various pharmaceutical activities. SAU has been suggested to exert beneficial effects for the treatment of hepatic steatosis [6], hepatocellular carcinoma [7], gastric cancer [8], and osteoarthritis [9] via multiple pathways. Furthermore, SAU has been reported to mediate various cellular pathways. For example, SAU could inhibit hepatic steatosis by reducing the expression of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9), and attenuate osteoarthritis inflammatory degeneration by suppressing IL-1β via the NF-κB and Nrf2/HO-1 pathways [6,[9], [10], [11]]. Moreover, SAU inhibits TGF-β1-induced epithelial-mesenchymal transition (EMT) in gastric cancer [8], and has been implicated as a potential novel therapeutic for allergic inflammatory diseases via inhibiting mast cell activation and anaphylaxis [12]. However, whether and how SAU mediates intestinal inflammation remains elusive.
In the current study, we performed in vitro and in vivo experiments to investigate the potential therapeutic anti-inflammatory abilities of SAU on the pathogenesis of intestinal inflammation, as well as determine the underlying mechanism. Our data reveal an uncharacterized mechanism whereby SAU regulates intestinal inflammation and Th17 differentiation, suggesting that SAU might serve as a new therapeutic approach for IBD.
Section snippets
Human samples
As reported previously [13,14], mucosal biopsies were collected from IBD patients and healthy individuals during colonoscopies, and peripheral blood CD4+ T cells were purified by using microbeads. All subjects were recruited from the Gastroenterology Department, Sichuan Provincial People’s Hospital (Chengdu, China). This study was approved by the Institutional Review Board for Clinical Research of the Sichuan Provincial People’s Hospital.
Mice and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis
Prdm1−/− mice were purchased from the Jackson Laboratory
SAU ameliorates TNBS-induced colitis in mice
To investigate the effects of SAU on regulating intestinal inflammation, we established TNBS-induced colitis in mice and treated them with SAU. TNBS-exposed mice without SAU treatment served as controls. SAU treatment significantly reduced the severity of TNBS-induced colitis, characterized by slighter weight loss and lower diarrhea and fecal blood scores than the controls (Fig. 1A–C). Pathological analysis of colon sections showed that SAU markedly mitigated mucosal injury by TNBS in the
Discussion
Although the precise mechanism of IBD remains unclear, dysregulated host immune responses mediated by CD4+ T cells are well-known to be a crucial player in the development and aggravation of the disease. Here, we revealed an uncharacterized role for SAU in the regulation of intestinal inflammation by suppressing Th17 differentiation but facilitating IL-10 production; moreover, SAU facilitated Th17 cell production of IL-10 via Blimp-1.
Different T cell subsets have diverse impacts on the
Funding
This research was funded by the National Natural Science Foundation of China (51603030).
Declaration of competing interest
The authors have declared that no conflict of interest exists.
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