Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Clin Lab Anal. 2022 Jun;36(6):e24455. doi: 10.1002/jcla.24455. Epub 2022 May 7.
Dioscin has been proven to have anti-cancer, anti-inflammatory, and anti-infection roles. However, the role of Dioscin in inflammatory bowel disease (IBD) and its related mechanisms is unclear and needs further study.
The colitis model in mice was established. After Dioscin (20, 40, or 80 mg/kg) treatment, the colon length was measured by a ruler. Histopathology, inflammatory cytokines, gut permeability, tight junction proteins, macrophage infiltration, macrophage polarization, and miR-125a-5p level were detected by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), FITC-dextran, Western blot, and flow cytometry. In vitro experiments, after RAW264.7 cells induced by lipopolysaccharide (LPS)/interleukin-4 (IL-4), were treated with Dioscin and miR-125a-5p inhibitor, miR-125a-5p level, cell vitality, inflammatory cytokines, and M1/M2 marker genes were measured by qRT-PCR and MTT assay.
Dioscin (20, 40, or 80 mg/kg) relieved DSS-triggered colitis and restrained the serum and colon of pro-inflammatory cytokines expression. Meanwhile, different concentrations' Dioscin weakened M1 macrophage polarization but facilitated tight junction protein expressions, M2 macrophage polarization, and miR-125a-5p level in colitic mice. Moreover, miR-125a-5p inhibitor reversed the modulation of Dioscin on miR-125a-5p expression, cell vitality, and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. We further discovered that Dioscin restrained M1 marker gene (CD16) expression while intensifying M2 marker genes (CD206 and Arginase-1) expressions in vitro, which was reversed by miR-125a-5p inhibitor.
Dioscin modulated macrophage polarization by increasing miR-125a-5p, thereby improving the intestinal epithelial barrier function and reducing IBD.
薯蓣皂苷元已被证明具有抗癌、抗炎和抗感染作用。然而，薯蓣皂苷元在炎症性肠病（IBD）中的作用及其相关机制尚不清楚，需要进一步研究。
建立小鼠结肠炎模型。经薯蓣皂苷元（20、40 或 80mg/kg）治疗后，用标尺测量结肠长度。通过苏木精-伊红染色、酶联免疫吸附试验、实时定量聚合酶链反应（qRT-PCR）、FITC-葡聚糖、Western blot 和流式细胞术检测组织病理学、炎症细胞因子、肠道通透性、紧密连接蛋白、巨噬细胞浸润、巨噬细胞极化和 miR-125a-5p 水平。在体外实验中，用脂多糖（LPS）/白细胞介素-4（IL-4）诱导 RAW264.7 细胞后，用薯蓣皂苷元和 miR-125a-5p 抑制剂处理，通过 qRT-PCR 和 MTT 测定 miR-125a-5p 水平、细胞活力、炎症细胞因子和 M1/M2 标记基因。
薯蓣皂苷元（20、40 或 80mg/kg）缓解 DSS 诱导的结肠炎，抑制血清和结肠中促炎细胞因子的表达。同时，不同浓度的薯蓣皂苷元减弱 M1 巨噬细胞极化，但促进紧密连接蛋白表达、M2 巨噬细胞极化和 colitic 小鼠中 miR-125a-5p 水平。此外，miR-125a-5p 抑制剂逆转了薯蓣皂苷元对 LPS 诱导的 RAW264.7 细胞中 miR-125a-5p 表达、细胞活力和炎症细胞因子的调节作用。我们进一步发现，薯蓣皂苷元在体外抑制 M1 标记基因（CD16）表达，同时增强 M2 标记基因（CD206 和精氨酸酶-1）的表达，而 miR-125a-5p 抑制剂则逆转了这一作用。
薯蓣皂苷元通过增加 miR-125a-5p 调节巨噬细胞极化，从而改善肠道上皮屏障功能，减轻 IBD。
