Standardized Fraction of Turbinaria ornata Alleviates Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice via Upregulation of FOXP3+ Regulatory T Cells.

Na-Hyun Kim,Yun Na Kim,You-Jin Jeon,Jung-Rae Rho,Seon Min Lee,Eun Ju Jeong,Jeong-Doo Heo

doi:10.3390/biom10101463

Abstract

Turbinaria ornata is a tropical brown algae (seaweed) known to have anti-inflammatory properties. In this study, we analyzed T. ornata extract (TOE) using liquid chromatography quadrupole time of flight mass spectrometry (LC-QTOF-MS) and nuclear magnetic resonance (NMR) and evaluated the in vivo efficacy of TOE against dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. The bioactive fraction of TOE was administered orally daily for 6 weeks to mice under different treatments normal, colitis, and colitis + conventional drug (5-aminosalicylic acid, 5-ASA). Regarding clinical manifestation, the disease activity index and colon length of the colitis + TOE group were significantly reduced compared to those of the colitis group. The results of myeloperoxidase activity and histopathological examination showed similar results. Western blot analysis of colon tissues revealed that cyclooxygenase-2, tumor necrosis factor alpha (TNF-α), and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) were significantly decreased in the colitis + 5-ASA group, whereas forkhead box P3 (FOXP3) was increased. qPCR results showed changes in T cell subsets; the administration of TOE upregulated regulatory T cell (Treg) expression, although T helper 17 cell (Th17) expression did not change significantly. Interestingly, the colitis + TOE group showed high levels of both Th1 and Th2 transcription factors, but the secreted cytokine interferon (IFN)-γ and interleukin (IL)-4 remained unchanged and somewhat reduced. Additionally, TNF-α gene expression was significantly reduced in the colitis + TOE group. IL-6 mRNA levels were also decreased, although not significantly. Four compounds were structurally elucidated using 1D- and 2D-NMR spectroscopy, and five compounds were fully identified or tentatively characterized using LC-QTOF-MS. In conclusion, TOE could alleviate chronic colitis via upregulation of Foxp3+ Treg cells and production of the anti-inflammatory cytokine IL-10, which directly inhibits macrophages and pro-inflammatory cytokine synthesis, leading to reduced colitis.

Highlights

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), which is an idiopathic, chronic obstructive disease with typical recurrent episodes of colitis symptoms [1,2]
The 1H nuclear magnetic resonance (NMR) spectrum of M2 is shown in Figure 1, which contains severely overlapped signals in the upfield and oxygen-bearing regions
Our research team reported the anti-inflammatory effect of T. ornata in an in vitro model of IBD comprising human epithelial Caco-2 and THP-1 macrophages [28]

Summary

Introduction

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), which is an idiopathic, chronic obstructive disease with typical recurrent episodes of colitis symptoms [1,2]. IBD is known to initiate when the intestinal epithelial barrier is broken down by toxic chemicals, pathogens, or idiopathic causes [6]. Once this barrier collapses, the underlying tissues are exposed and attacked by gut microbiota, leading to the recruitment of leukocytes into the lamina propria and causing uncontrolled inflammation [6]. TNF-α is a major pathological cytokine that can affect the activation and progression of colitis by including direct disruption of the intestinal epithelial barrier integrity, provocation of epithelial cell death, and co-stimulation of effector T cells toward further chronic inflammation [9,10]

Methods

Results

Conclusion