College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.
Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
DNA Cell Biol. 2024 Oct;43(10):520-536. doi: 10.1089/dna.2024.0101. Epub 2024 Aug 26.
Isoorientin (ISO) is a naturally occurring flavonoid with diverse functional properties that mitigate the risk of diseases stemming from oxidation, inflammation, and cancer cell proliferation. P-glycoprotein (P-gp) is a vital component of the intestinal epithelium and may play a role in the onset of intestinal inflammatory conditions, such as inflammatory bowel disease (IBD). Recent studies have suggested that short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) produced by the gut microbiota stimulate the increase of P-gp expression, alleviating excessive inflammation and thereby preservation of intestinal homeostasis. ISO has been shown to improve colon health and modulate the gut microbiota. In this study, we aimed to explore whether ISO can modulate the microbes and their metabolites to influence P-gp expression to alleviate IBD. First, the impact of ISO on dextran sulfate sodium (DSS)-treated colitis in mice was investigated. Second, 16S rRNA gene sequencing was conducted. The present study indicated that ISO mitigated the symptoms and pathological damage associated with DSS-treated colitis in mice. Western blot analysis revealed ISO upregulated P-gp in colon tissues, suggesting the critical role of P-gp protein in intestinal epithelial cells. 16S microbial diversity sequencing revealed ISO restored the richness and variety of intestinal microorganisms in colitis-bearing mice and enriched SCFA-producing bacteria, such as . The experiments also revealed that the ISO fecal microbiota transplantation (FMT) inoculation of DSS-treated mice had similarly beneficial results. FMT mice showed a reduction in colitis symptoms, which was more pronounced in ISO-FMT than in CON-FMT mice. Meanwhile, ISO-FMT expanded the abundance of beneficial microorganisms, increased the expression of metabolites, such as SCFAs and total SBAs, and significantly upregulated the expression of P-gp protein. In addition, Spearman's correlation analysis demonstrated a positive correlation between the production of SCFAs and SBAs and the expression of P-gp. The present study identified that ISO increases the expression of P-gp in the intestinal epithelium by regulating intestinal microorganisms and their metabolites, which maintains colonic homeostasis, improves the integrity of the colonic epithelium, and alleviates colitis.
异甘草素（ISO）是一种天然存在的类黄酮，具有多种功能特性，可降低氧化、炎症和癌细胞增殖导致疾病的风险。P-糖蛋白（P-gp）是肠上皮的重要组成部分，可能在肠道炎症性疾病（如炎症性肠病（IBD））的发病中发挥作用。最近的研究表明，肠道微生物群产生的短链脂肪酸（SCFAs）和次级胆汁酸（SBAs）刺激 P-gp 表达的增加，从而减轻过度炎症并维持肠道内环境平衡。ISO 已被证明可改善结肠健康并调节肠道微生物群。在这项研究中，我们旨在探讨 ISO 是否可以调节微生物及其代谢物来影响 P-gp 表达，从而缓解 IBD。首先，研究了 ISO 对葡聚糖硫酸钠（DSS）处理的结肠炎小鼠的影响。其次，进行了 16S rRNA 基因测序。本研究表明，ISO 减轻了 DSS 处理的结肠炎小鼠的症状和病理损伤。Western blot 分析显示 ISO 在上皮细胞中上调 P-gp 的表达，表明 P-gp 蛋白在肠上皮细胞中的关键作用。16S 微生物多样性测序显示 ISO 恢复了结肠炎小鼠肠道微生物的丰富度和多样性，并丰富了产生 SCFA 的细菌，如 。实验还表明，ISO 粪便微生物群移植（FMT）接种 DSS 处理的小鼠也具有类似的有益效果。FMT 小鼠的结肠炎症状减轻，ISO-FMT 组比 CON-FMT 组更为明显。同时，ISO-FMT 扩大了有益微生物的丰度，增加了代谢物（如 SCFA 和总 SBA）的表达，并显著上调了 P-gp 蛋白的表达。此外，Spearman 相关性分析表明 SCFAs 和 SBAs 的产生与 P-gp 的表达呈正相关。本研究表明，ISO 通过调节肠道微生物及其代谢物增加肠上皮细胞中 P-gp 的表达，从而维持结肠内环境平衡，改善结肠上皮完整性，缓解结肠炎。
