Abstract：
Immune response and inflammation highly contribute to many metabolic syndromes such as inflammatory bowel disease (IBD), ageing and cancer with disruption of host metabolic homeostasis and the gut microbiome. Icariin-1 (GH01), a small-molecule flavonoid derived from Epimedium, has been shown to protect against systemic inflammation. However, the molecular mechanisms by which GH01 ameliorates ulcerative colitis via regulation of microbiota-mediated macrophages polarization remain elusive. In this study, we found that GH01 effectively ameliorated dextran sulfate sodium (DSS)-induced colitis symptoms in mice. Disruption of intestinal barrier function, commensal microbiota and its metabolites were also significantly restored by GH01 in a dose-dependent manner. Of note, we also found that GH01 enhanced phagocytic ability of macrophages and switched macrophage phenotype from M1 to M2 both in vitro and in vivo. Such macrophage polarization was highly associated with intestinal barrier integrity and the gut microbial community. Consequently, GH01 exhibited strong anti-inflammatory capacity by inhibiting TLR4 and NF-κB pathways and proinflammatory factors (IL-6). These findings suggested that GH01 might be a potential nutritional intervention strategy for IBD treatment with the gut microbial community-meditated macrophage as the therapeutic targets.
摘要：
免疫反应和炎症高度促进许多代谢综合征，如炎症性肠病（IBD），衰老和癌症与宿主代谢稳态和肠道微生物组的破坏。淫羊藿苷-1（GH01），一种来源于淫羊藿的小分子类黄酮，已被证明可以预防全身性炎症。然而,GH01通过调节微生物群介导的巨噬细胞极化来改善溃疡性结肠炎的分子机制仍然难以捉摸.在这项研究中,我们发现GH01能有效改善葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎症状。肠屏障功能的破坏，GH01也以剂量依赖性方式显着恢复了共生微生物群及其代谢产物。值得注意的是，我们还发现GH01在体外和体内增强了巨噬细胞的吞噬能力，并将巨噬细胞表型从M1转换为M2。这种巨噬细胞极化与肠屏障完整性和肠道微生物群落高度相关。因此,GH01通过抑制TLR4和NF-κB通路和促炎因子（IL-6）而表现出较强的抗炎能力。这些发现表明，GH01可能是IBD治疗的一种潜在营养干预策略，以肠道微生物群落介导的巨噬细胞为治疗靶点。
