School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China.
World J Gastroenterol. 2019 Sep 14;25(34):5134-5151. doi: 10.3748/wjg.v25.i34.5134.
Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency, abdominal pain and diarrhea. It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome (IBS), is a common functional bowel disease. Its main symptoms are recurrent abdominal pain, diarrhea, constipation or alternations between diarrhea and constipation. There are obvious differences in metabolites between TCM syndromes. By comparing the body fluid metabolism maps of model animals, metabolomics can discover disease biomarkers, analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body. Thus, the evaluation of animal models tends to be comprehensive and objective. This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.
To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.
Wistar rats were used to establish IBS models, and then randomly divided into four groups: A model control group and three Tong Xie Yao Fang treatment groups (high, medium and low doses). A normal, non-IBS group was established. The rats were treated for 2 wk. On days 0 and 14 of the experimental model, urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Nine potential biomarkers were identified, and six major metabolic pathways were found to be related to IBS.
In the study of metabonomics, nine potential biomarkers including L-serine, 4-methylgallic acid, L-threonine, succinylacetone, prolyl-hydroxyproline, valyl-serine, acetyl citrate, marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine, which were assigned to amino acids, organic acids, succinyl and glycosides. Furthermore, the metabolic pathway of L-serine, L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes, which mainly involved the metabolism of cysteine and methionine, vitamin B6 metabolism, serotonin synapse, tryptophan metabolism, sphingolipid metabolism, digestion, absorption of protein and amino acid metabolism. These pathways are related to intestinal dysfunction, inflammatory syndrome, nervous system dysfunction and other diseases.
Tong Xie Yao Fang has pharmacological effects on IBS, and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.
痛泻要方是治疗肝脾两虚、腹痛腹泻的代表中药方剂。它在治疗包括肠易激综合征(IBS)在内的胃肠道功能障碍方面具有独特的作用,是一种常见的功能性肠病。其主要症状为反复发作的腹痛、腹泻、便秘或腹泻与便秘交替。中医证候的代谢物存在明显差异。通过比较模型动物的体液代谢图谱,代谢组学可以发现疾病生物标志物,分析代谢途径的差异,并了解体内物质的病理过程和代谢途径。因此,动物模型的评估趋于全面和客观。这可能为痛泻要方与 IBS 模型之间的相互作用提供进一步的了解。
采用代谢组学方法评价痛泻要方对 IBS 大鼠的作用。
采用 Wistar 大鼠建立 IBS 模型,随机分为模型对照组和痛泻要方高、中、低剂量治疗组 3 组,另设正常、非 IBS 组。实验模型第 0、14 天,收集大鼠 12 h 尿液进行超高效液相色谱-四极杆飞行时间质谱分析。共鉴定出 9 个潜在生物标志物,发现与 IBS 相关的 6 条主要代谢途径。
在代谢组学研究中,在尿液中鉴定出 9 个潜在生物标志物,包括 L-丝氨酸、4-甲基没食子酸、L-苏氨酸、丁二酰丙酮、脯氨酰-羟脯氨酸、缬氨酸-丝氨酸、乙酰柠檬酸、马钱素鼠李糖苷和 5-羟基-L-色氨酸,这些标志物被分配到氨基酸、有机酸、丁二酰和糖苷。此外,在京都基因与基因组百科全书中发现了 L-丝氨酸、L-苏氨酸和 5-羟基-L-色氨酸的代谢途径,主要涉及半胱氨酸和蛋氨酸代谢、维生素 B6 代谢、血清素突触、色氨酸代谢、鞘脂代谢、蛋白质消化吸收和氨基酸代谢。这些途径与肠道功能障碍、炎症综合征、神经系统功能障碍等疾病有关。
痛泻要方对 IBS 具有药理作用,其机制可能与上述尿液中 9 个潜在生物标志物的代谢有关。