Traditional Chinese Medicine Compound Yi Sugar Health Intervention On Curative Effect Evaluation Of The Metabolic Syndrome And Metabolomics Research

Purpose: Metabolic Syndrome is a combination of risk factors including obesity,high blood sugar(diabetes or impaired glucose regulation),dyslipidemia(hypertriglyceridemia and/or low high-density lipoproteincholesterol), hypertension,which can seriously affect the health of the body.These factors are directly contributed to the occurrence of atheroscleroticcardiovascular disease and increase the risk of type2diabetes. In thisprospective study, the object of study is the metabolic syndrome and impairedglucose regulation,and in line with the TCM diagnosis.Randomized,double-blind, parallel-group, multicenter clinical trial methods are used asresearch methods, the main inspection targets include glucose, lipids, bloodpressure, glycosylated hemoglobin and body mass index. We observed theeffectiveness of traditional Chinese medicine Yi Tangkang treatmentingmetabolic syndrome and the lifestyle intervention+traditional Chinese medicineYi Tangkang. Metabolomics focuses on the metabolic pathways of metabolism ofendogenous substances including whole-organ or tissue and metabolism of theoverall change in trajectory suffered internal and external factors, reflecta series of biological events that occured in certain pathophysiological process.In this study, by copying the spleen deficiency syndrome metabolic syndrome ratmodel, we researched model plasma specimens by metabolomics and looked for spleendeficiency syndrome metabolic syndrome lesions characteristic metabolites,observed metabolite changes related to physiological and pathological, exploredthe molecular mechanism of spleen deficiency syndrome metabolic syndrome lesionsand further revealled the essence of spleen deficiency syndrome metabolicsyndrome. We explained traditional Chinese medicine Yi Tangkang interventionmechanism and targets of interpretation from the point of view of endogenousmetabolites by using metabolomics technology and methods, Material and method:1. Clinical researchDouble-blind, parallel-group, multicenter clinical trial methods are used asresearch methods.We Collected165metabolic syndrome in line with the TCMdiagnostic criteria. Patients were randomly assigned to two groups. Treatmentgroups: lifestyle intervention (diet, exercise)+traditional Chinese medicine.Control group: Lifestyle intervention (diet, exercise)+Chinese medicineplacebo. In the entire clinical trial period,we analyzed all cases ofbaseline(epidemiological data, safety indicators, indicators of effectiveness).We observed the data and indicators of treatment and control groups before thetest and the existence of comparable. In all cases a variety of indicators ofeffectiveness,including the main effect indicators (blood glucose, blood lipids,blood pressure,glycosylated hemoglobin)and indicators of secondary effects(weight, waist circumference, BMI, and TCM syndromeindicators, traditionalChinese medicine syndrome indicators, quality of life points, etc.) have beenanalyzed.We compared the data and established a compliance rate criterion. Wehave observed that the traditional Chinese medicine Yi Tangkang and Chinese andWestern medicine combined with the clinical efficacy of the treatment program.We compared the safety index concerned with the blood, urine, stool routine,liver function, renal function, etc and observe the security of trial medicationChinese herbal compound Yi Tangkang.2. Experimental study2.1Replication of animal disease models30healthy male SD rats, weighing (180±20) g, were randomly divided intotwo groups after adaptive feeding days. Blank control group (n=10) and modelgroup (n=30). The model group were fed cabbage15~20g/a rat in a singleday and allowed to drink water freely, swimm to the endurance limit. The modelgroup were fed high sugar, high fat diet feeding in double day, a total of12weeks. W looked forward to Copy the model of spleen deficiency syndrome andmetabolic syndrome.2.2metabolomics studies Spleen deficiency syndrome and metabolic syndrome rats were dividedrandomly into two groups: model group (n=6) and model+TCM group (n=6).Weused ultra high performance liquid chromatography–quadrupole–time offlight mass spectrometry(UPLC/Q-TOF-MS)technology and detected smallmolecule metabolites in plasma. We builted a UPLC/Q-TOF-MS-MS blood totalion chromatogram and getted a metabolic fingerprint which were Were analyzedusing principal Component Analysis and Partial Least Squares-DiscriminantAnalysis.We identified the differences in characteristics of metabolites andFound some biomarkers, traced their sources and metabolic pathways. Accordingto the clinical patient day of Chinese medicine dosage were converted into theratequivalent dose, once a day orally, for4weeks. After the end of the UPLC/Q-TOF-MS-MS detection,we observed the group differences in changes of plasmasmall-molecule metabolites spectrum of the spleen deficiency syndrome andmetabolic syndrome model.Results:1.Clinical trials:1.1Baseline analysis: Demographic data baseline: age, sex distribution,no significant difference between the two groups（P＞0.05）. Duration baseline:systolic blood pressure, diastolic blood pressure, fasting glucose,2-hourpostprandialblood glucose, glycosylated hemoglobin,no significantdifference between the two groups（P＞0.05）. The primary efficacy endpointbaseline:no significant difference between the two groups （P＞0.05）Secondary outcome measures baseline: Weight, waist circumference, hipcircumference, BMI,, TCM syndromes total points, the survival scale scoring,no significant difference between the two groups（P＞0.05）.1.2Analysis of efectiveness: lifestyle intervention can significantlyreduce the2-hour postprandial blood glucose,blood pressure and BMI.After the intervention of Chinese herbal compound Yi Tangkang,2hours postprandial blood sugar, blood pressure and BMI had been improved, triglycerides and total cholesterol declined, improved fasting blood glucose,LDL and HDL, improve the compliance rate of fasting plasma glucose, twohours postprandial blood sugar, high-density lipoprotein, blood pressure andBMI. Chinese herbal compound Yi Tangkang can improve effectively the mainclinical symptoms and general condition of MS patients, whileimproving patient quality of life.1.3Security analysis: the safety index of the two groups before and aftertreatment were not statistically different (P>0.05). Chinese herbalcompound Yi Tang Kang is safe.2.Animal experiments:2.1Animal disease model experiment: rats showed swimming endurance decreased,eat less lazy, loose stools thin, spiritual malaise, body Mao Guangliang degreediminished.The weight began to increase significantly after the the four weeks,fasting blood glucose increased after the the sixr weeks,triglycerides and highdensity lipoprotein showed abnormal after the the two weeks. Rats showedhyperinsulinemia, insulin resistance Lining with spleen deficiency syndrome andmetabolic syndrome evaluation criteria.2.2Metabolomics studies: The original mass spectrometry data wered importedinto MarkerLynx package and completed the pre-treatment of the peakidentification, peak alignment and baseline correction,outputedthree-dimensional matrix last. The processed data matrix wered imported Simca-Psoftware (version11.5)to analyze PCA, PLS-DA, OPLS-DA. there were significantdifferences in each grouping blood metabolic spectrum. We found a number ofpotential biomarkers related to the metabolic syndrome rat modelof spleendeficiency syndrome: N-acetyl-D-glucosamine, lysophosphatidylcholine,sphingomyelin,5-methylcytosine, Melanostatin, Genistein, Prostaglandin A2,homocysteine, L-Homoserine. The collection of these substances togetherconstitute the Spleen Deficiency Syndromemetabolic syndrome rat model ofmetabolic group characteristics and are the results of the carbohydrates, lipids,proteins and other metabolic disorders.4weeks of treatment by traditional Chinese medicine Yi Tangkang, LPC、SM、HCY decreased, some new biologically activesubstances appeared: diacylglycerol,6-Keto-prostaglandin F1a, phenylalanine,galactosylsphingosine, Biocytin,which showing metabolic network repairment,the whole metabolic spectrum returned to the normal range.Conclusions:1. Lifestyle intervention in metabolic syndrome (to maintain properweight, proper exercise, changes in diet to reduce calorieintake, avoid smoking and a modest reduction indrinking, etc.) canreduce the2-hour postprandial blood glucose, blood pressure andBMI.2. Yi Tangkang, a Chinese herbal formula, can not only lower blood sugar, bloodpressure, regulation of lipid metabolism disorders to reduce the risk factorsof metabolic syndrome, can also improve the clinical symptoms of the metabolicsyndrome and TCM syndromes, while improving the quality of life of patients andsafe non-toxic.3. Lifestyle intervention+Chinese medicine treatment options in clinicalefficacy is superior to the simple lifestyle interventions,which can delay thedevelopment of spleen deficiency syndrome and metabolic syndrome condition andshould be widely applied.4. Weary plus improper diet (high sugar, high fat diet) modeling method can besuccessfully copied spleen deficiency syndrome and metabolic syndrome in animalmodels.5.N-acetyl-D-glucosamine, lysophosphatidylcholine, sphingomyelin,5-methylcytosine, Melanostatin, Genistein, Prostaglandin A2, homocysteine,L-Homoserine. The collection of these substances together constitute the SpleenDeficiency Syndromemetabolic syndrome rat model of metabolic groupcharacteristics and are the results of the carbohydrates, lipids, proteins andother metabolic disorders.6. Chinese herbal compound Yi Tangkang shows the multi-channel, multi-target,two-way adjustment features. LPC、SM、HCY decreased, some new biologically active substances appeared: diacylglycerol,6-Keto-prostaglandin F1a, phenylalanine,galactosylsphingosine, Biocytin,which showing metabolic network repairment,the whole metabolic spectrum returned to the normal range.7. Metabonomics is a good platform to study the mechanism of metabolic syndromeand traditional Chinese medicine.