Zhao Huan, Hu Xueli, Guan Shenghong, Cai Jinhong, Li Wei, Zhang Di, Feng Yue, Zhu Wei, Marzorati Massimo, Li Bing, Zhang Xiaoyong, Tian Jingkui
Key Laboratory for Molecular Medicine and Chinese Medicine Preparations, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China; Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Key Laboratory for Molecular Medicine and Chinese Medicine Preparations, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Int Immunopharmacol. 2025 Jan 27;146:113858. doi: 10.1016/j.intimp.2024.113858. Epub 2024 Dec 20.
Ulcerative colitis is a chronic idiopathic inflammatory disease that impacts the mucous membrane of the colon. Lately, the incidence and prevalence of UC has been increasing globally. However, there are significant side effects of existing drugs for UC intervention. Accordingly, there is a pressing demand to explore novel bioactive substances for addressing UC. Natural product saponins have attracted great attention due to their obvious anti-colitis potential. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia capillipes Hemsl., exhibits good anti-inflammatory activity. Nonetheless, the impact and mechanism of CPS-A on ulcerative colitis remains obscure. This study aimed to investigate the therapeutic effects of CPS-A on the dextran sulphate sodium induced colitis mouse model and explore its mechanism. The efficacy and safety of CPS-A were evaluated in a well-established dextran sodium sulfate (DSS)-induced colitis mice model. Disease progression was monitored via clinical symptoms, histopathological examination, quantification of inflammatory cytokines, and epithelial barrier function evaluation. Plasma samples and intestinal contents were collected for non-targeted metabolomics and 16sRNA sequencing, respectively, to jointly evaluate the mechanism of action. CPS-A alleviated colitis by improving weight, Disease activity index score, histopathology, goblet cell, colon length, and expression of inflammatory factors. Moreover, CPS-A effectively preserved the integrity of the intestinal barrier by enhancing the expression of tight junction proteins and mucin in the colonic tissue of mice. Furthermore, CPS-A exerted a regulatory effect on the composition of the gut microbiota, promoting bacterial richness and diversity. It not only suppressed the abundance of detrimental bacteria while enhancing the abundance of advantageous bacteria, but also modulated the metabolites derived from the intestinal flora. Importantly, correlation analysis shows that these indicators are highly correlated. This study revealed that CPS-A exhibits a favorable therapeutic efficacy against colitis, primarily attributed to its ability to modulate the gut microbiota their associated metabolites as the key mechanisms of action.
溃疡性结肠炎是一种影响结肠黏膜的慢性特发性炎症性疾病。近来，全球范围内溃疡性结肠炎的发病率和患病率一直在上升。然而，现有用于干预溃疡性结肠炎的药物存在显著的副作用。因此，迫切需要探索用于治疗溃疡性结肠炎的新型生物活性物质。天然产物皂苷因其明显的抗结肠炎潜力而备受关注。山慈菇苷A是一种三萜皂苷，来源于细梗香草，具有良好的抗炎活性。尽管如此，山慈菇苷A对溃疡性结肠炎的影响及其机制仍不清楚。本研究旨在探讨山慈菇苷A对葡聚糖硫酸钠诱导的结肠炎小鼠模型的治疗作用，并探索其作用机制。在已建立的葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中评估了山慈菇苷A的疗效和安全性。通过临床症状、组织病理学检查、炎症细胞因子定量以及上皮屏障功能评估来监测疾病进展。分别收集血浆样本和肠道内容物用于非靶向代谢组学和16sRNA测序，以联合评估其作用机制。山慈菇苷A通过改善体重、疾病活动指数评分、组织病理学、杯状细胞、结肠长度以及炎症因子表达来减轻结肠炎。此外，山慈菇苷A通过增强小鼠结肠组织中紧密连接蛋白和黏蛋白的表达有效地维持了肠道屏障的完整性。此外，山慈菇苷A对肠道微生物群的组成发挥调节作用，促进细菌丰富度和多样性。它不仅抑制有害细菌的丰度，同时增强有益细菌的丰度，还调节肠道菌群衍生的代谢产物。重要的是，相关性分析表明这些指标高度相关。本研究表明，山慈菇苷A对结肠炎具有良好的治疗效果，其主要作用机制是调节肠道微生物群及其相关代谢产物。
