Objective: To observe the effect of Mongolian medicine Geixigune-3 granules on urine metabolomics in constipation rats, and search for related metabolites and metabolic pathways. Methods: Rats were randomly divided into 4 groups: blank group, model group, Geixigune-3 granules group and positive drug(mosapride) group. The constipation model of rats was established by subcutaneous injection of loperamide hydrochloride. The 24 h urine volume, fecal weight, number of fecal particals and moisture content of rats in each group were observed. After the model was successfully established, corresponding drugs were given for treatment. ACQUITY UPLC® BEH Shield RP 18(100 mm×2.1 mm, 1.7 μm) column with a 0. 1% formic acid water and acetonitrile containing 0.1% formic acid as mobile phase were used. Gradient elution was applied and the flow rate was 0.35 mL·min-1. ESI with positive and negative ionspattern was used. Rat urine was analzed to identify differential metabolites and metabolic pathways. Results: Compared with the model group, the 24 h urine volume decreased (P<0.05), the fecal weight increased(P<0.01), the number of particals increased(P<0.05), and the moisture content increased(P<0.01) in the Geixigune-3 granules group. A total of 22 differential metabolites were identified, of which the levels of furosemide, polyporapyranone D, uridine 2',3'-cyclic phosphate increased after administration, and the levels of cysteinyl-lysine, didesmethyl doxepin and N-gluconyl ethanolamine decreased after administration, mainly involving tryptophan metabolism, ubiquinone and other terpenoid-quinone biosynthesis and steroid biosynthesis. Conclusion: Geixigune-3 granules has a regulating effect on urine metabolites of constipation model rats, which lays an effective experimental foundation for further treating constipation with Geixigune-3 granules.
BAO Ze-yang, MENG He, DU Li-na, BAO Su-ri-gao, HAN E-er-de-mu-tu, MENG Yong-mei
. Urine metabolomics of constipated rats treated with Mongolian medicine Geixigune-3 granules based on UPLC-Q Tof MS/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(7)
: 1205
-1212
.
DOI: 10.16155/j.0254-1793.2023.07.14
[1] KARTAL A, YALCIN M, CITGEZ B, et al. The effect of chronic constipation on the development of inguinal herniation[J].Hernia, 2017, 21(4): 531
[2] 黎彩凤, 高启霞, 沙子珺, 等. 慢性便秘的发病机制及中医药防治概述[J].山东中医杂志, 2021, 40(8): 895
LI CF, GAO QX, SHA ZJ, et al. Pathogenesis of chronic constipation and its prevention and treatment with traditional Chinese medicine[J].Shandong J Tradit Chin Med, 2021, 40(8):895
[3] 黄亚娟, 蒋士生, 向燕芳. 洛哌丁胺对大鼠慢传输型便秘模型的稳定性研究[J].湖南中医杂志, 2020, 36(7): 153
HUANG YJ, JIANG SS, XIANG YF. Stability of loperamide in rat model of slow transit constipation[J].Hunan J Tradit Chin Med, 2020, 36(7): 153
[4] HERRICK LM, SPALDING WM, SAITO YA, et al. A case-control comparison of direct healthcare-provider medical costs of chronic idiopathic constipation and irritable bowel syndrome with constipation in a community-based cohort[J].J Med Econ, 2017, 20(3): 273
[5] 四部医典. 第4部[S].2013: 594
The Four Medical Tantras. Vol Ⅳ[S].2013: 594
[6] 内蒙古蒙成药标准[S].1984: 260
Standard for Mongolian Patent Medicine in Inner Mongolia[S].1984: 260
[7] 包玉华, 良良, 郭丽娟, 等. 蒙成药给喜古纳-3汤研究进展[J].内蒙古民族大学学报(自然科学版), 2021, 36(2): 154
BAO YH, LIANG L, GUO LJ, et al. Research progress of Mongolian patent medicine Geixigune-3 decoction[J].Inner Mongolian Univ(Nat Sci Ed), 2021, 36(2): 154
[8] 蒙古学百科全书编辑委员会. 蒙古学百科全书(医学)[M].呼和浩特:内蒙古人民出版社, 2002: 623
Editorial Board of Encyclopedia of Mongolian Studies. Encyclopedia of Mongolian Studies (Medicine)[M].Hohhot: Inner Mongolia People's Publishing House, 2002: 623
[9] WANT EJ, WILSON ID, GIKA H, et al. Global metabolic profiling procedures for urine using UPLC-MS[J].Nat Protoc, 2010, 5(6):1005-18
[10] 邵晓妮, 吴美薇, 黑亚南, 等. 慢性高尿酸血症肾病模型大鼠尿液和肾脏的代谢组学研究[J].中国药理学通报, 2020, 36(11): 1607
HAO SN, WU MW, HEI YN, et al. Metabonomics study of urine and kidney in rats with chronic hyperuricemia nephropathy[J].Chin Pharm Bull, 2020, 36(11): 1607
[11] COMAI S, BERTAZZO A, BRUGHERA M, et al. Tryptophan in health and disease[J].Adv Clin Chem, 2020, 95: 165
[12] PLATTEN M, NOLLEN EAA, RÖHRIG UF, et al. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond[J].Nat Rev Drug Discov, 2019, 18(5): 379
[13] MAWE GM, HOFFMAN JM. Serotonin signalling in the gut―functions, dysfunctions and therapeutic targets[J].Nat Rev Gastroenterol Hepatol, 2013, 10(8): 473
[14] 陈鹏, 王琛, 罗瑞熙, 等. 大黄素通过调节血清代谢改善神经病理性疼痛的机制研究[J].中国中药杂志, 2022, 47(8): 2187
CHEN P, WANG C, LUO RX, et al. Study on the mechanism of emodin improving neuropathic pain by regulating serum metabolism[J].China J Chin Mater Med, 2022, 47(8): 2187
[15] SCHIFFER L, BARNARD L, BARANOWSKI ES, et al. Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review[J].J Steroid Biochem Mol Biol, 2019, 194: 105439
[16] CHEN JQ, CHEN YY, TAO HJ, et al. An integrated metabolomics strategy to reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats[J].J Pharm Biomed Anal, 2020, 177: 112837
[17] ABBY SS, KAZEMZADEH K, VRAGNIAU C, et al. Advances in bacterial pathways for the biosynthesis of ubiquinone[J].Biochim Biophys Acta Bioenerg, 2020, 1861(11): 148259
[18] 聂银利, 段学清, 陈瑞, 等. 大黄对大鼠肠道菌群的影响[J].实用中医药杂志, 2021, 37(4): 529
NIE YL, DUAN XQ, CHEN R, et al. Effect of rhubarb on intestinal flora in rats[J].J Pract Tradit Chin Med, 2021, 37(4): 529
