Inflammatory bowel disease (IBD), which consists of ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract. Occurrence and development of UC have been associated with multiple potential causative factors, which include fungal dysbiosis. Growing evidence reveals that Candida albicans-associated dysbiosis is correlated with clinical deterioration in UC. Paeonol (PAE) is a commonly used traditional medicine with multiple reported properties including effective alleviation of UC. In this study, a murine UC model was established by colonizing mice with additional C. albicans via gavage prior to dextran sodium sulfate (DSS) administration. Effects of PAE treatment were also assessed at initiation and in preestablished C. albicans-associated colitis. The results showed that C. albicans supplementation could aggravate disease activity index (DAI), compromise mucosal integrity, exacerbate fecal and tissue fungal burdens, increase serum β-glucan and anti-Saccharomyces cerevisiae antibody (ASCA) levels, promote serum and colonic tissue pro-inflammatory cytokine secretion (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8) and decrease the anti-inflammatory cytokine IL-10 level. It also stimulated Dectin-1, TLR2 and TLR4 as well as expression of their downstream effector NF-κB in colonic tissue. After PAE treatment, the adverse impacts of C. albicans on colitis were relieved, via decreased receptor-associated local and systemic inflammation. Our study suggests that PAE should be a candidate for treatment of fungal dysbiosis-associated UC and may act through the Dectin-1/NF-κB pathway in collaboration with TLR2 and TLR4.

中文翻译：

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丹皮酚减轻葡聚糖硫酸钠诱导的涉及白色念珠菌相关菌群失调的结肠炎

炎症性肠病 (IBD) 由溃疡性结肠炎 (UC) 和克罗恩病 (CD) 组成，是一种胃肠道慢性炎症性疾病。UC的发生和发展与多种潜在的致病因素有关，其中包括真菌失调。越来越多的证据表明，与白色念珠菌相关的生态失调与 UC 的临床恶化相关。丹皮酚 (PAE) 是一种常用的传统药物，具有多种报道特性，包括有效缓解 UC。在这项研究中，在葡聚糖硫酸钠 (DSS) 给药之前，通过管饲法将额外的白色念珠菌定殖于小鼠，从而建立了小鼠 UC 模型。PAE 治疗的效果也在开始时和预先建立的白色念珠菌相关性结肠炎。结果表明，补充白色念珠菌可加重疾病活动指数 (DAI)、损害黏膜完整性、加重粪便和组织真菌负荷、增加血清 β-葡聚糖和抗酿酒酵母抗体 (ASCA) 水平，促进血清和结肠组织的增殖。 -炎性细胞因子分泌（肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6和IL-8）并降低抗炎细胞因子IL-10水平。它还刺激了 Dectin-1、TLR2 和 TLR4 以及它们下游效应子 NF-κB 在结肠组织中的表达。PAE处理后，白色念珠菌的不良影响通过减少受体相关的局部和全身炎症，结肠炎得到缓解。我们的研究表明，PAE 应该是治疗真菌失调相关 UC 的候选药物，并且可能通过 Dectin-1/NF-κB 通路与 TLR2 和 TLR4 合作发挥作用。