| Shengyu Decoction could date back to the Lan Shi Mi Zang.It is composed of raw rehmannia glutinosa,cooked rehmannia glutinosa,Ligusticum chuanxiong,ginseng,Angelica angelica and astragalus.The formulas has the power of invigorating “qi” and “blood”.The National Administration of TCM,together with the National Medical Products Administration,added it into the Catalogue of Famous Ancient Classics(The First Batch)in 2018,and treat “qi and blood deficiency” and other disease syndromes.Clinical experience shows that Shengyu decoction has the effect of invigorating “qi” and “blood”,and treating “qi and blood deficiency”,but its mechanism is not clear.In order to study the mechanism and metabolic pathways of Shengyu Decoction,atmospheric oxygen resistance model,chronic fatigue model and blood deficiency model were built in this reserch,using GC-MS and HPLC-MS technology to detect these three models.A relevant model of metabolic profile and a metabolic network diagram were built by t-test to screen relevant differences metabolites,and reveal of the mechanism of Shengyu Decoction to resist metabolic oxygen,fatigue and to enrichblood,which provided a basis for Shengyu Decoction’s pharmacological action mechanism and clinical research.The results were as follows:1.Study on metabonomics of hronic fatigue effect of Shengyu DecoctionTo study the therapeutic effect of Shengyu Decoction on chronic fatigue,chronic fatigue model was established: the model was modeled by the multi-factor influence of basic diet,chronic restraint and exhausted swimming.The experimental data of exhaustive swimming time,body weight change,organ index and tail suspension in rats were compared,the blood lactic acid measurement method was established through HPLC-MS to replace the traditional method,and the automatic analysis of the instrument was used to shorten the lactic acid measurement time and provide a quantitative,fast,high-throughput analysis method.GC-MS was used to analyze the serum,a total of 19 differences were screened,such as pyruvate,acetylglycine,oxalic acid,glycerol.After administration of Shengyu Decoction,19 disordered metabolites were significantly adjusted.And 5 metabolic pathways that were highly related to the anti-fatigue model were obtained: glyceride metabolism,pyruvate metabolism,Glycine,serine and threonine metabolism and so on.GC-MS and HPLC-MS were used to analyze the urine samples of the rats,and a total of 30 different metabolites such as succinic acid,malic acid,aconitic acid,hippuric acid and threonine were screened out.The content of related differential metabolites were significantly recalled after intervention of Shengyu Decoction.5 metabolic pathways related to the anti-fatigue model were Ascorbate and aldarate metabolism,Glyoxylate and dicarboxylate metabolism,Valine,leucine and isoleucine biosynthesis,TCA cycle,etc.The results showed that Shengyu Decoction significantly prolonged the swimming time of rats,slowed down the trend of weight loss,eliminated the accumulation of lactic acid during the modeling process,and achieved the anti-fatigue effect by intervening in energy and amino acid metabolism.2.Study on anti-hypoxic metabonomics of Shengyu DecoctionIn order to explore the anti-hypoxia mechanism of Shengyu Decoction,the anti-hypoxia model was established under normal pressure and the survival time and blood data of mice were recorded.After the blood sample was derivatized,it was analyzed by GC-MS,and the differential metabolite information were obtained after multivariate statistics.The results showed that Shengyu Decoction could significantly prolong the survival time of mice,and obtained a total of 17 different metabolites related to the anti-hypoxia model,namely 1-butanol,glycine,betaine,methylsuccinic acid,and γ-amino Butyric acid,lactic acid,pyruvate,L-cystine,galactose-1-phosphate,erythritol,lauric acid,tridecanoic acid,myristic acid,pyroglutamic acid,isoleic acid,ceric acid,cholesterol.Through the construction of enriched metabolic pathways and metabolic network diagrams,it had found that 5 metabolic pathways were related to the model,namely: pyruvate metabolism,glycine,threonine,and serine metabolism,Alanine,aspartate and glutamate metabolism,Citrate cycle,glycolysis or gluconeogenesis.After the intervention of each administration group of Shengyu Decoction,the levels of lactic acid,pyruvate and other substances in hypoxic mice were significantly increased,and the level of glycine was down-regulated,indicating that Shengyu Decoction might produce anti-hypoxic effects by affecting the body’s energy metabolism.3.Study on Metabonomics of Shengyu Decoction for Blood DeficiencyThe blood deficiency animal model was established by cyclophosphamide and acetophenazine,the weight,blood routine data,and thymus and spleen organ indexes of the mice were analyzed.The red blood cell index increased,indicating that Shengyu Decoction could restores the number of peripheral blood cells and had a certain effect of nourishing blood.GC-MS was used to analyze serum of the blood-deficiency mouse,16 different metabolites related to blood-deficiency model were obtained.Comparison of the regulating effect of different doses of Shengyu Decoction on the differential metabolites in mice serum showed that Shengyu Decoction could significantly adjust the levels of 16 metabolites.The enrichment results of metabolic pathways showed that the pathways related to the intervention mechanism of Shengyu Decoction mainly involved pyruvate metabolism and glyceride metabolism.It was speculated that Shengyu Decoction might interfere the body’s energy metabolism process to produce therapeutic effects.Therefore,metabonomics methods were used to search for differential metabolites and enrich the metabolic pathways in this study.The results showed that the anti-fatigue,anti-hypoxia,and treatment of blood deficiency mechanisms of Shengyu Decoction might involve energy metabolism and amino acid metabolism and so on to improve the anti-fatigue ability,enhance the anti-hypoxia ability and produce blood tonic effect.This study analyzed the mechanism of Shengyu Decoction in treating diseases and provided a basis for the clinical application of Shengyu Decoction. |
PDF Full Text Request