Interpretation of Euphorbia Kansui Stir-Fried with Vinegar Treating Malignant Ascites by a UPLC-Q-TOF/MS Based Rat Serum and Urine Metabolomics Strategy Coupled with Network Pharmacology

Abstract

Euphorbia kansui stir-fried with vinegar (V-kansui) has promising biological activities toward treating malignant ascites with reduced toxicity compared to crude kansui. But the mechanism concerning promoting the excretion of ascites has not been systematically studied. The purpose of this paper was to investigate the possible mechanism of V-kansui in treating malignant ascites, including metabolic pathways and molecular mechanism using an integrated serum and urine metabolomics coupled with network pharmacology. Serum and urine samples of rats were collected and analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A comparison with crude kansui was also made to demonstrate the feasibility of processing. Principle component analysis (PCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were conducted to discriminate the groups, search important variables and reveal the possible pathways. A compound-target-metabolite network was finally constructed to identify the crucial targets to further understand the molecular mechanism. Sixteen significant metabolites contributing to the discrimination of model and control groups were tentatively screened out. They were mainly involved in the arachidonic acid metabolism, steroid hormone biosynthesis and primary bile acid to possibly reduce inflammatory and modulate the renin-angiotensin-aldosterone system to achieve treating malignant ascites. A bio-network starting from the compounds and ending in the metabolites was constructed to elucidate the molecular mechanism. HSP90AA1, ANXA2, PRDX6, PCNA, SOD2 and ALB were identified as the potential key targets that were responsible for the treatment of malignant ascites by the parameter combining the average shortest path length and betweenness centrality. The correlated 17 compounds were considered as the potential active ingredients in V-kansui. In addition, the metabolomics showed that the effect of V-kansui was almost in accordance with crude kansui. These results systematically revealed the mechanism of V-kansui against malignant ascites for the first time using metabolomics coupled with network pharmacology. V-kansui could be a promising safe and therapeutic medicine for the excretion of ascites.

Systematic characterization of the chemical constituents in vitro and prototypes in vivo of Dingkun Dan using ultra‐high‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry combined with the UNIFI™ software

“…The others were identified by exact molecular weight, characteristic fragments, and the literature (Liu et al, 2013;Zhang et al, 2018).…”

Mechanism of Curcuma wenyujin Rhizoma on Acute Blood Stasis in Rats Based on a UPLC-Q/TOF-MS Metabolomics and Network Approach

“…They only focus on changes in metabolites and cannot find the material basis for efficacy and effect targets. Network pharmacology can make up this defect very well in TCM study [32]. Network pharmacology is a new pattern of drug research to analyze the relationship between drugs, targets, metabolic pathways, and diseases by constructing a network model [33,34].…”

A “Green” Homogenate Extraction Coupled with UHPLC-MS for the Rapid Determination of Diterpenoids in Croton Crassifolius

“…Although there were clear differences in the content of various sample sources, the sources could hardly be distinguished. The differences or similarity of multivariate data can be visualized through PCA as unsupervised multivariate-data analysis [ 15 ]. In this study, PCA was used to distinguish the 12 batches of C. crassifolius and samples were well separated by this PCA method.…”