Geng Runyi, Cao Yongqing, Liu Te, Zhong Shenglan
Department of Anorectal Surgery, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Department of Anorectal, School of Medicine, Shanghai Fourth People's Hospital, Tongji University, 1279 Sanmen Road, Shanghai, 200434, China.
Int J Colorectal Dis. 2025 Aug 5;40(1):169. doi: 10.1007/s00384-025-04974-y.
As the inflammatory bowel disease subtype, ulcerative colitis (UC) is the idiopathic chronic inflammatory condition affecting colonic mucosa. Characterized by high incidence and therapeutic challenges, UC imposes significant burdens on global health. β-Sitosterol, a phytosterol abundant in fruit and medicinal plants, has demonstrated potential anti-inflammatory properties.
Herein, the UC mouse model was created by administering dextran sulfate sodium, followed by β-sitosterol treatment. Histopathology, single-cell RNA-sequencing (scRNA-seq), Kyoto Encyclopedia of Genes and Genomes (KEGG), flow cytometry (FCM), enzyme-linked immunosorbent assays (ELISAs), Western blotting, and quantitative real-time reverse transcription PCR (qRT-PCR) were implemented.
Oral administration of β-sitosterol markedly alleviated intestinal damage and inflammation in UC mice. The scRNA-seq assay revealed that the immune cell subpopulations in the colorectal tissues of mice treated by β-sitosterol gavage apparently decreased compared with them in UC mice, with the most significant difference in the number of macrophages. KEGG analysis predicted significant downregulation of ribosome pathway activity in CD68 + MΦ1 macrophages following β-sitosterol treatment. Both FCM and ELISA analyses showed that β-sitosterol significantly downregulated inflammatory factor generation like interleukin-1β (IL-1β) and inducible nitrous oxide synthase (iNOS) by RAW264.7-derived MΦ1 macrophages. In vitro, as confirmed by qRT-PCR and Western blotting analyses, β-sitosterol dramatically inhibited MΦ1 macrophage expression of ribosome pathway core factors.
The present study confirmed that β-sitosterol inhibits MΦ1 macrophage polarization and inflammatory activity by downregulating the key gene transcriptional activity and expression in ribosome signaling pathway in MΦ1 macrophages, thereby ameliorating UC symptoms in mice.
作为炎症性肠病的亚型，溃疡性结肠炎（UC）是一种影响结肠黏膜的特发性慢性炎症性疾病。UC发病率高且治疗具有挑战性，给全球健康带来了重大负担。β-谷甾醇是一种在水果和药用植物中含量丰富的植物甾醇，已显示出潜在的抗炎特性。
在此，通过给予葡聚糖硫酸钠建立UC小鼠模型，随后进行β-谷甾醇治疗。实施了组织病理学、单细胞RNA测序（scRNA-seq）、京都基因与基因组百科全书（KEGG）、流式细胞术（FCM）、酶联免疫吸附测定（ELISA）、蛋白质印迹法和定量实时逆转录PCR（qRT-PCR）。
口服β-谷甾醇可显著减轻UC小鼠的肠道损伤和炎症。scRNA-seq分析显示，与UC小鼠相比，经β-谷甾醇灌胃处理的小鼠结肠直肠组织中的免疫细胞亚群明显减少，其中巨噬细胞数量差异最为显著。KEGG分析预测，β-谷甾醇治疗后CD68+MΦ1巨噬细胞中核糖体途径活性显著下调。FCM和ELISA分析均表明，β-谷甾醇可显著下调RAW264.7来源的MΦ1巨噬细胞产生的白细胞介素-1β（IL-1β）和诱导型一氧化氮合酶（iNOS）等炎症因子。在体外，经qRT-PCR和蛋白质印迹法分析证实，β-谷甾醇可显著抑制MΦ1巨噬细胞中核糖体途径核心因子的表达。
本研究证实，β-谷甾醇通过下调MΦ1巨噬细胞核糖体信号通路中的关键基因转录活性和表达，抑制MΦ1巨噬细胞极化和炎症活性，从而改善小鼠UC症状。
