ABSTRACT
Plasma nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving kidney deficient in mice of Polygoni Multiflori Radix Praeparata. Thirty-five ICR mice were randomly divided into the control group, the model group, the BB24 h (braising with black bean sauce for 24 hours) group, the BB32 h group, and the BB40 h group. Biochemical indices in blood plasma of mice were measured by collecting eye blood after modeling. Changes in plasma endogenous metabolites of mice from each group were determined by ultra-performance liquid chromatography-linear trap quadrupole-orbitrap XL (UPLC-LTQ-orbitrap XL), and differential metabolites were screened. The results of pharmacodynamic investigation showed that compared to the model group, the levels of estradiol increased obviously in the BB24 h (P < 0.05), and the levels of cortisol increased obviously in BB32 h (P < 0.05). The hormone level of mice with kidney deficiency was significantly improved after taking processed Polygonum multiflorum. A total of 70 differential endogenous metabolites in blood plasma of mice were identified from all treatment groups, which mainly involved glycerophospholipid meta-bolism, arachidonic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and linoleic acid metabolism. The study indicated that Polygoni Multiflori Radix Praeparata may play the role of tonifying liver and kidney by improving the disorder of hypothalamic-pituitary-adrenal axis and regulating lipid metabolism in mice. Correlation analysis on differential metabolites in blood plasma and the chemical constituents showed that stilbene glycosides and saccharides may be the key pharmacodynamic material basis. The present study provides a new reference and theoretical foundation for revealing the potential pharmacodynamic material basis and mechanism investigation on tonifying liver and kidney of Polygoni Multiflori Radix Praeparata. This study was carried out following the ethical guidelines and regulations for the use of laboratory animals of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and passed the animal experimental ethical review [No. SYXK (Jing) 2019-0003].
ABSTRACT
Objective: To observe the changes of urine metabolic profile of Wuzhuyu Decoction in rats with deficiency cold and vomit, and explore its possible mechanism of treatment of deficiency cold and vomit syndrome. Methods: A rat model of deficiency cold and vomit was prepared by a composite method (rhucax + cisplatin). Rats were randomly divided into control group, model group, and Wuzhuyu Decoction group. UPLC-MS/MS combined with principal component analysis and partial least squares analysis were used to analyze urine data and identify potential biomarkers. Diversified ROC curves were used to validate differential metabolites; Pathway Analysis database was used for topological analysis of differential metabolites; R and Cytoscape were used for correlation analysis and modular analysis of metabolites. Results: The urine metabolic spectrum of control group and model group were completely separated. Wuzhuyu Decoction group was close to the control group, indicating that the model was successfully replicated; And Wuzhuyu Decoction can interfere with the symptoms of deficiency cold and vomit in rats, suggesting that the rat body had a tendency to return to normal state. Through modular analysis of 34 urine differential metabolites, the deficiency cold and vomit treatment was revealed to affect biosynthesis of valine, leucine and isoleucine, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, tryptophan metabolism, tyrosine metabolism, arachidonic acid metabolism, citric acid cycle (TCA cycle) pathways. Modularity analysis revealed that there was close relationship between 10 modules; Alanine, leucine, tyrosine, tryptophan, isoleucine, succinic acid, alanine, fumaric acid, malic acid, isocitrate, and other biological targets can thus be used as markers of deficiency cold and vomit. Conclusion: Wuzhuyu Decoction can improve the physiological characteristics of the model of deficiency cold and vomit. The mechanism may be related to the regulation of amino acid metabolism, energy metabolism and lipid metabolism in rats.