College of Animal Science, Jilin University, Changchun, China.
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.
Phytomedicine. 2024 Jul 25;130:155741. doi: 10.1016/j.phymed.2024.155741. Epub 2024 May 15.
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.
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.
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.
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.
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.
溃疡性结肠炎（UC）是一种慢性复发性肠道疾病，目前缺乏有效的治疗方法。熊果苷是一种从熊果叶中提取的糖苷，可调节许多病理过程。然而，熊果苷对 UC 的作用尚不清楚。
本研究旨在探讨熊果苷在缓解结肠炎中的作用及其在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中的潜在机制。
在 C75BL/6 J 小鼠中，用 DSS 诱导结肠炎，同时口服熊果苷（50 和 100 mg/kg），通过评估疾病活动指数（DAI）评分、结肠长度和组织病理学来评估其疗效。采用阿尔辛蓝过碘酸希夫（AB-PAS）染色、免疫组织化学（IHC）、免疫荧光（IF）和末端转移酶介导的 dUTP 缺口末端标记（Tunel）染色评估肠道屏障功能。采用流式细胞术、双 IF 和蛋白质印迹（WB）检测熊果苷对体内和体外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 16S rRNA 基因测序分析小鼠肠道微生物群。
结果表明，熊果苷能保护小鼠免受 DSS 诱导的结肠炎，表现为 DAI 评分降低和肠道病理损伤减轻。熊果苷减少炎症因子的分泌，显著调节中性粒细胞的功能，并通过 ErK 依赖性途径抑制 NETs 的形成，通过体内和体外实验证实了其对结肠炎的抵抗作用。同时，重塑肠道菌群结构，增加肠道微生物多样性和丰富度，特别是增加益生菌和产丁酸菌的丰度，进一步促进了对结肠炎的保护作用。
熊果苷通过抑制 NETs 的形成、维持黏膜屏障的完整性和塑造肠道微生物群的组成，促进肠道内环境的稳定，从而缓解 DSS 诱导的结肠炎。本研究为合理使用熊果苷预防结肠炎等相关疾病提供了科学依据。
