Abstract：
BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent intestinal disease lacking effective treatments. β-arbutin, a glycoside extracted from the Arctostaphylos uva-ursi leaves, that can regulate many pathological processes. However, the effects of β-arbutin on UC remain unknown.
OBJECTIVE: In this study, we investigated the role of β-arbutin in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis.
METHODS: In C75BL/6 J mice, DSS was used to induce colitis and concomitantly β-arbutin (50 and 100 mg/kg) was taken orally to evaluate its curative effect by evaluating disease activity index (DAI) score, colon length and histopathology. Alcian blue periodic acid schiff (AB-PAS) staining, immunohistochemistry (IHC), immunofluorescence (IF) and TdT-mediated dUTP Nick-End Labeling (Tunel) staining were used to assess intestinal barrier function. Flow cytometry, double-IF and western blotting (WB) were performed to verify the regulatory mechanism of β-arbutin on neutrophil extracellular traps (NETs) in vivo and in vitro. NETs depletion experiments were used to demonstrate the role of NETs in UC. Subsequently, the 16S rRNA gene sequencing was used to analyze the intestinal microflora of mouse.
RESULTS: Our results showed that β-arbutin can protect mice from DSS-induced colitis characterized by a lower DAI score and intestinal pathological damage. β-arbutin reduced inflammatory factors secretion, notably regulated neutrophil functions, and inhibited NETs formation in an ErK-dependent pathway, contributing to the resistance to colitis as demonstrated by in vivo and in vitro experiments. Meanwhile, remodeled the intestinal flora structure and increased the diversity and richness of intestinal microbiota, especially the abundance of probiotics and butyric acid-producing bacteria. It further promoted the protective effect in the resistance of colitis.
CONCLUSIONS: β-arbutin promoted the maintenance of intestinal homeostasis by inhibiting NETs formation, maintaining mucosal-barrier integrity, and shaping gut-microbiota composition, thereby alleviating DSS-induced colitis. This study provided a scientific basis for the rational use of β-arbutin in preventing colitis and other related diseases.
OBJECTIVE: In this study, we investigated the role of β-arbutin in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis.
METHODS: In C75BL/6 J mice, DSS was used to induce colitis and concomitantly β-arbutin (50 and 100 mg/kg) was taken orally to evaluate its curative effect by evaluating disease activity index (DAI) score, colon length and histopathology. Alcian blue periodic acid schiff (AB-PAS) staining, immunohistochemistry (IHC), immunofluorescence (IF) and TdT-mediated dUTP Nick-End Labeling (Tunel) staining were used to assess intestinal barrier function. Flow cytometry, double-IF and western blotting (WB) were performed to verify the regulatory mechanism of β-arbutin on neutrophil extracellular traps (NETs) in vivo and in vitro. NETs depletion experiments were used to demonstrate the role of NETs in UC. Subsequently, the 16S rRNA gene sequencing was used to analyze the intestinal microflora of mouse.
RESULTS: Our results showed that β-arbutin can protect mice from DSS-induced colitis characterized by a lower DAI score and intestinal pathological damage. β-arbutin reduced inflammatory factors secretion, notably regulated neutrophil functions, and inhibited NETs formation in an ErK-dependent pathway, contributing to the resistance to colitis as demonstrated by in vivo and in vitro experiments. Meanwhile, remodeled the intestinal flora structure and increased the diversity and richness of intestinal microbiota, especially the abundance of probiotics and butyric acid-producing bacteria. It further promoted the protective effect in the resistance of colitis.
CONCLUSIONS: β-arbutin promoted the maintenance of intestinal homeostasis by inhibiting NETs formation, maintaining mucosal-barrier integrity, and shaping gut-microbiota composition, thereby alleviating DSS-induced colitis. This study provided a scientific basis for the rational use of β-arbutin in preventing colitis and other related diseases.
摘要：
背景：溃疡性结肠炎（UC）是一种慢性复发性肠道疾病，缺乏有效的治疗方法。β-熊果苷，从Arctostyplosuva-ursi叶中提取的糖苷，可以调节许多病理过程。然而,β-熊果苷对UC的作用尚不清楚。
目的：在本研究中，我们研究了β-熊果苷在缓解结肠炎中的作用,并探讨了其在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型中的潜在机制.
方法：在C75BL/6J小鼠中，用DSS诱导结肠炎，同时口服β-熊果苷（50和100mg/kg），通过评估疾病活动指数（DAI）评分来评价其疗效。结肠长度和组织病理学。阿尔辛蓝高碘酸希夫（AB-PAS）染色，免疫组织化学（IHC），免疫荧光（IF）和TdT介导的dUTP尼克末端标记（Tunel）染色用于评估肠屏障功能。流式细胞术,进行了双IF和蛋白质印迹（WB），以验证体内和体外β-熊果苷对中性粒细胞胞外陷阱（NETs）的调节机制。NETs耗竭实验用于证明NETs在UC中的作用。随后，采用16SrRNA基因测序技术对小鼠肠道菌群进行分析。
结果：我们的结果表明，β-熊果苷可以保护小鼠免受DSS诱导的结肠炎，其特征是DAI评分降低和肠道病理损伤。β-熊果苷减少炎症因子的分泌，特别是中性粒细胞功能的调节，并抑制ErK依赖性途径中的NETs形成，体内和体外实验证明了对结肠炎的抵抗力。同时,重塑了肠道菌群结构，增加了肠道菌群的多样性和丰富度，尤其是丰富的益生菌和产生丁酸的细菌。它进一步促进了结肠炎抗性的保护作用。
结论：β-熊果苷通过抑制NETs的形成促进肠道稳态的维持，保持粘膜屏障的完整性，和塑造肠道微生物群组成，从而减轻DSS诱导的结肠炎。本研究为合理使用β-熊果苷预防结肠炎等相关疾病提供了科学依据。
目的：在本研究中，我们研究了β-熊果苷在缓解结肠炎中的作用,并探讨了其在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型中的潜在机制.
方法：在C75BL/6J小鼠中，用DSS诱导结肠炎，同时口服β-熊果苷（50和100mg/kg），通过评估疾病活动指数（DAI）评分来评价其疗效。结肠长度和组织病理学。阿尔辛蓝高碘酸希夫（AB-PAS）染色，免疫组织化学（IHC），免疫荧光（IF）和TdT介导的dUTP尼克末端标记（Tunel）染色用于评估肠屏障功能。流式细胞术,进行了双IF和蛋白质印迹（WB），以验证体内和体外β-熊果苷对中性粒细胞胞外陷阱（NETs）的调节机制。NETs耗竭实验用于证明NETs在UC中的作用。随后，采用16SrRNA基因测序技术对小鼠肠道菌群进行分析。
结果：我们的结果表明，β-熊果苷可以保护小鼠免受DSS诱导的结肠炎，其特征是DAI评分降低和肠道病理损伤。β-熊果苷减少炎症因子的分泌，特别是中性粒细胞功能的调节，并抑制ErK依赖性途径中的NETs形成，体内和体外实验证明了对结肠炎的抵抗力。同时,重塑了肠道菌群结构，增加了肠道菌群的多样性和丰富度，尤其是丰富的益生菌和产生丁酸的细菌。它进一步促进了结肠炎抗性的保护作用。
结论：β-熊果苷通过抑制NETs的形成促进肠道稳态的维持，保持粘膜屏障的完整性，和塑造肠道微生物群组成，从而减轻DSS诱导的结肠炎。本研究为合理使用β-熊果苷预防结肠炎等相关疾病提供了科学依据。
