Sodium houttuyfonate attenuates dextran sulfate sodium associated colitis precolonized with Candida albicans through inducing β-glucan exposure

鱼腥草素钠通过诱导 β-葡聚糖暴露减轻白色念珠菌预定植的葡聚糖硫酸钠相关性结肠炎

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作者:Kelong Ma, Mengli Chen, Juanjuan Liu, Yuzhu Ge, Tianming Wang, Daqiang Wu, Guiming Yan, Changzhong Wang, Jing Shao

Abstract

Inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis is a chronic intestinal disease most likely associated with gut dysbiosis. Candida related mycobiota has been demonstrated to play a role in IBD progression. Traditional Chinese herbal medicines (TCHMs) with antifungal activity have a potential in prevention and treatment of fungi-related IBD. Sodium houttuyfonate (SH) is a promising anti-Candida TCHMs. In this study, a dextran sulfate sodium induced colitis model with Candida albicans precolonization is established. SH gavage can significantly decrease the fungal burdens in feces and colon tissues, reduce disease activity index score, elongate colon length, and attenuate colonic damages. Moreover, SH markedly inhibits the levels of anti-Saccharomyces cerevisiae antibodies, β-glucan, and proinflammatory cytokine (IL-1β, IL-6, IL-8, TNF-α), and increases anti-inflammatory factor IL-10 level in serum and colon tissue. Further experiments demonstrate that SH could induce β-glucan exposure, priming intestinal macrophages to get rid of colonized C. albicans through the collaboration of Dectin-1 and TLR2/4. With the decreased fungal burden, the protein levels of Dectin-1, TLR2, TLR4, and NF-κBp65 are fallen back, indicating the primed macrophages calm down and the colitis is alleviated. Collectively, these results manifest that SH can attenuate C. albicans associated colitis via β-glucan exposure, deepening our understanding of TCHMs in the prevention and treatment of fungi associated IBD.

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