UPLC-QTOF-MS-Based Metabolomics Reveal the Effect of Polysaccharides from Danggui-Shaoyao-San in Type 2 Diabetic Male and Female Rats

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is currently one of the most prominent and global chronic conditions. In recent years, it has been found that macromolecular polysaccharide has a significant effect on T2DM, various polysaccharides such as Angelica Sinensis Polysaccharide (ASP), Poriacocos polysaccharide and Atractylodesmacrocephala polysaccharide in DSS have effects on T2DM, but mechanism of polysaccharides of DSS(p-DSS) at the metabolic level is still unclear. The purpose of this work is to study the male and female mechanisms of p-DSS in treating T2DM based on metabolomics. Materials and Methods: In this study, metabolomics was used to elucidate the therapeutic mechanism of DSS in T2DM. Urinary samples were collected from male and female rats with T2DM, induced by a high-sugar and high-fat diet combined with Streptozotocin (STZ), to measure the levels of biochemical markers. Urinary metabolomics-based analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was conducted to evaluate the differential metabolites from multiple metabolic pathways. Results: After treatment with p-DSS for 4 weeks, biochemical indicators, including Fasting Blood Glucose (FBG), Fasting Insulin (FINS), Oral Glucose Tolerance Test (OGTT), Insulin Tolerance Test (ITT) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), were significantly improved. Metabolomics results revealed that p-DSS regulated the biomarkers, such as PC, 2-oxoglutarate, NAAG in TCA cycle and alanine, aspartate and glutamate metabolism for male rats, on the contrary, leukotriene B4, cholic acid in arachidonic acid metabolism and primary bile acid biosynthesis for female rats. Conclusions: Based on metabolomics, the mechanisms of p- DSS in male and female rats are not identical.