Qiu Chuan-Wei, Zhang Yi, Luo Zhen-Ye, Zhang Feng-Lin, Xia Ting, Chen Fei-Long, Tan Xiao-Mei, Liu Chang-Shun
Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, School of Traditional Chinese Medicine, Southern Medical University Guangzhou 510515, China.
Zhongguo Zhong Yao Za Zhi. 2024 Aug;49(16):4420-4426. doi: 10.19540/j.cnki.cjcmm.20240318.301.
Based on the differences in targeted energy metabolomics, intestinal barrier protein expression, and glucose transport,the synergistic mechanism of Coptidis Rhizoma(CR) processed with Euodiae Fructus(ECR) on ulcerative colitis(UC) was explored.Mice were administered 4% dextran sulfate sodium to induce UC model, and then randomly divided into a model group, a CR group,and an ECR group. After 14 days of treatment, the therapeutic effect of processing on UC was assessed through histopathology of colon tissue and inflammatory indexes. Targeted energy metabolomics analysis was performed to evaluate the effect of processing on colon tissue energy metabolism. Molecular docking was carried out to predict the binding affinity of energy metabolites with intestinal barrier tight junction protein Claudin and glucose transporter 2(GLUT2). In vivo unidirectional intestinal perfusion experiments in rats were conducted to evaluate the effect of processing on intestinal glucose transport. The results showed that both CR and ECR could repair colon tissue damage in UC mice, downregulate tissue inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)levels, with the efficacy of ECR being superior to CR. Processed products significantly upregulated levels of multiple metabolites in colon tissue glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation, among which the upregulated levels of 1,6-diphosphate fructose and acetyl coenzyme A could bind well with Claudin and GLUT2. Additionally, the processed product also increased the expression of GLUT2 and enhanced glucose transport activity. This study suggests that ECR may enhance glucose transport to improve colon energy metabolism, promote barrier repair, and exert synergistic effects through processing.
基于靶向能量代谢组学、肠道屏障蛋白表达和葡萄糖转运的差异，探讨了黄连（CR）与吴茱萸（ECR）配伍对溃疡性结肠炎（UC）的协同作用机制。给小鼠灌胃4%葡聚糖硫酸钠诱导UC模型，然后随机分为模型组、CR组和ECR组。治疗14天后，通过结肠组织病理检查和炎症指标评估炮制对UC的治疗效果。进行靶向能量代谢组学分析以评估炮制对结肠组织能量代谢的影响。进行分子对接以预测能量代谢产物与肠道屏障紧密连接蛋白Claudin和葡萄糖转运蛋白2（GLUT2）的结合亲和力。在大鼠体内进行单向肠道灌注实验以评估炮制对肠道葡萄糖转运的影响。结果表明，CR和ECR均可修复UC小鼠的结肠组织损伤，下调组织炎症因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平，其中ECR的疗效优于CR。炮制产物显著上调结肠组织糖酵解、三羧酸循环和氧化磷酸化中多种代谢产物的水平，其中上调的1,6-二磷酸果糖和乙酰辅酶A水平可与Claudin和GLUT2良好结合。此外，炮制产物还增加了GLUT2的表达并增强了葡萄糖转运活性。本研究表明，ECR可能通过增强葡萄糖转运来改善结肠能量代谢，促进屏障修复，并通过炮制发挥协同作用。
