Liu Yao-Yu, Mu Fang-Yuan, Wang Yi-Cheng, Wang Man-Yu, Wang Chun-Guo, Yan Xing-Li
College of Chinese Traditional Medicine, Beijing University of Chinese Medicine Beijing 100029, China.
Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine Beijing 100029, China.
Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(3):678-684. doi: 10.19540/j.cnki.cjcmm.20201119.201.
The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.
本研究旨在探讨蜘蛛香提取物对母婴分离联合三种应激因素诱导的腹泻型肠易激综合征(IBS-D)大鼠模型的药效学作用,并观察干预后粪便中内源性代谢产物的变化,寻找潜在生物标志物及相关代谢途径。通过母婴分离联合束缚、冰浴游泳和夹尾建立IBS-D动物模型。从腹部退缩反射压力阈值、粪便含水量和强迫游泳试验不动时间方面评价蜘蛛香提取物各剂量组的治疗效果。另外,收集大鼠粪便,采用超高效液相色谱-线性离子阱-静电场轨道阱质谱平台检测小分子代谢产物的代谢谱,运用主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)等多元统计分析方法寻找差异代谢生物标志物。结果显示,与正常组相比,模型组腹部退缩反射压力阈值降低、粪便含水量增加、强迫游泳试验不动时间延长。粪便代谢组学结果显示,39种代谢产物水平下调,37种代谢产物水平上调。进一步分析表明,这些代谢产物与胆汁酸代谢、不饱和脂肪酸代谢、氨基酸代谢、神经酰胺代谢等代谢途径有关。本研究证明蜘蛛香提取物对IBS-D模型大鼠有确切的药效学作用,并从粪便代谢组学角度探讨了其作用机制。