| Lycium barbarum polysaccharide(LBP)is the main bioactive substance from dried Goji berry,which has shown the ability of anti-tumor,immunity improvement,liver damage recovery,prevention of diabetes,etc.So far the LBP related researches on the improvement of type 2 diabetes(T2D)have been confirmed in human,animal and in vitro studies.LBP could reduce blood glucose levels,improve insulin resistance and maintain beta cell function in T2D patients,animals and in vitro experiments,however,the specific mechanism behind above function remains unclear.Metabolomics is a rapidly developing discipline,following genomics and proteomics,as a branch of system biology.Metabolomics explores the change pattern of quality and quantity of various metabolites interfered by external factors.Human nutrition-related metabolomics has become a new method for screening dietary trophic dietary markers However,no metabolomics studies on plant polysaccharide-related population was explored on T2D population intervention.Based on the previous research of LBP in our lab,we explored the bibliometric study on Goji and clarified the hot area of Goji,which was confirmed to be LBP and diabetes in the past 20 years;conducted the serum and urine metabolomics study on the effects of LBP intervention in healthy male;identified the different metabolites between obese and hyperlipidemia in T2D population and T2D population;examined the potential function effects of LBP on T2D patients via serum metabolomics;ultimately observe the effects of different doses of LBP on glycogen synthesis and amino acid metabolism enzymes of HepG2 cell lines with being induced insulin resistance model.The present thesis may provide new tools and ideas to help systematically study the intervention of LBP on different populations and promote further studies on LBP.The main research work is as follows1.Bibliometric analysis of world-wide publications on Goji berry from 2000 to 2018The present study aimed to systematically identify and analyze the publications on Goji berry from 2000 to 2018 published on the Web of Science(WOS)TM Core Collection utilizing bibliometric analysis.Electrical literatures were downloaded as the text format from the WOS database by the Mesh term search with "lycium barbarum" from 2000 to 2018,and were limited to articles and reviews in English.VOSviewer software was used to visualize all dataA total of 976 publications(914 articles and 62 reviews)were retrieved.A sum of 31 countries and areas contributed to the Goji berry publications during the period from 2000 to 2018.People's Republic of China was the leading country of 31 countries,accounting for 64.34%(n=628)publications.A total of 979 institutions contributed to the topic of Goji berry area Chinese Academy of Sciences produced the highest number of publications accounted for 8.2%of all publications.The density visualization map showed that keywords of "fruit","polysaccharides","cells","antioxidant activity","lycium barbarum","oxidative stress" and"mice" were in the hot areas of research.Besides,from the cluster map was divided into three categories including structural features,LBP(lycium barbarum polysaccharides)exploration and function verification.The relationship between Lycium barbarum polysaccharides intervention and diabetes is the research hot area recently,however,systematic mechanism researches remain unclear.2.Metabolic effects of dietary supplementation of Lycium barbarum polysaccharides on serum and urine metabolomics in a young healthy male populationLBP is the main bioactive compound extracted from Goji berry.Nutrition intervention could influence the metabolic profiles in human studies,which can be solved by application of metabolomics.However,the effects of polysaccharides on the in vivo remain unclear.Besides,However,barely any evidence provides useful information of metabolomics among phytochemicals,which is an important part of dietary intake with benefits of disease prevention and health promotion.Therefore,we investigated the serum and urine metabolomics effects of LBP,extracted from Lycium barbarum,on healthy male population.42 males were randomly divided into LBP supplementation(300 mg/d)and control group for 4 weeks,followed by anthropometric,biochemical indexes,and metabolic profiles detection.GC-TOF-MS and SIMCA software were used to detect metaolibtes and perform related data analysis.Dietary LBP supplementation decreased the TG/HDL index significantly.D-talose decreased,phosphate and leucine increased significantly in serum.4-Hydroxymandelonitrile 1 increased,and tyrosine 1,3-Aminoisobutyric acid 1,threitol and ribose decreased significantly in urine.Eight metabolites were simultaneously assessed by indicating the glycerophospholipid metabolism and tyrosine metabolism after LBP supplementation in males.3.Obesity or hyperlipidemia affect serum metabolites in type 2 diabetic patientsObesity and dyslipidemia are risk factors for insulin resistance and T2D development.The potential mechanism of progression of diabetes by the metabolomics approach is still unclear.Metabolome is defined as all small-molecule metabolites found or produced in an organism,comprises the smallest set of biomarkers,contributing to the understanding of the mechanism,diagnosis,and personalized medicine for diabetes due to the environmental and biological changes.This study aims to identify the metabolites related to T2D and T2D combined with obesity or hyperlipidemia.78 participatants were included including 20 healthy participants,20 T2D patients,12 T2D patients combined with obesity,26 T2D patients combined with hyperlipidemia.Then we recorded all participants' phycial examination indexes,collected blood samples to determine liver function,renal function,blood glucose,blood lipids,blood insulin and metabolites levels by utilizing GC-TOF-MS and SIMCA software to detect metaolibtes and related data analysis.Thus,we investigated the serum metabolomics in T2D patients with/without lipid dysfunction and healthy subjects.Some common metabolic profiles were found between T2D with/without obesity or hyperlipidemia and healthy controls.The results showed that serum lactose and myristic acid levels decreased and xylose 2,3-hydroxypropionc acid 1,N-ethylglycine 1 and farnesal 2 levels increased in all T2D patients,compared to the healthy subjects.Furthermore,serum urea and 3-hydroxypropionic acid 1 levels decreased and bis-(2-hydroxypropyl)-amine 2 level increased for T2D patients with obesity or hyperlipidemia,compared to the T2D patients.Interestingly,we observed the different serum metabolic profiles between T2D patients with obesity and hyperlipidemia when compared with T2D patients,which indicated the different underlying mechanism between obesity and hyperlipidemia.Serum phenylacetic acid and 2-monopalmitin levels decreased and aspartic acid 1,D-glyceric acid,tyrosine 1,threitol,glutamic acid and piceatannol 2 levels increased in T2D patients with obesity,compared to T2D patients.However,the metabolic profiles changed between T2D patients with hyperlipidemia and T2D patients,and serum glycine 2,cysteine,2-hydroxypyridine,pyruvic acid,3-hydroxypyruvate,tartronic acid and N-ethylmaleamic acid 3 levels decreased and 2-keto-isovaleric acid 1,glucose-6-phosphate 2,2'-deoxyadenosine 5'-momophosphate levels increased in T2D patients with hyperlipidemia.Further pathway analysis was conducted to explore the potential mechanism.Amino acid metabolism was disturbed for T2D patients with/without obesity or hyperlipidemia mainly including D-glutamine and D-glutamate metabolism,taurine and hypotaurine metabolism,beta-alanine metabolism,alanine,aspartate and glutamate metabolism,arginine and proline metabolism,glyoxylate and dicarboxylate metabolism and glycine,serine and threonine metabolism,and glycine,serine and threonine metabolism.In addition,the potential mechanism for obesity and hyperlipidemia in T2D patients was explored as well,which indicates that beta-alanine metabolism,glycine,serine and threonine,arginine and proline,and pyruvate metabolism may be involved in the T2D patients with obesity or hyperlipidemia compared with T2D patients.4.The metabolomics study of lycium barbarum polysaccharides on type 2 daibetic patientsThe present study further investigated the metabolomics effects of LBP on the T2D patients.To minimize the variation between different samples,we observed the metabolomics changes before and after 3 months of intervention in the same population with 20 T2D patients(300mg/d LBP).GC-TOF-MS was used to detect different metabolits and SIMCA software was used to perform related data analysisThis is the first study to investigate the metabolic effects of LBP on T2D population.Daily intake of 300mg/d LBP for 3 months reduced the fasting blood glucose levels in T2D population,significantly increase serum IGFBP(insulin-like growth factor binding protein)levels,reduced the serum levels of phosphate,cystine,arachidonic acid,urea,pyruvic acid,fructose 2,6-diphosphate degradation product 2,2-deoxytetracarboxylic acid,3-hydroxypropionic acid 1,glucose heptanoic acid 1,4-amino Butyric acid3,5,7-dihydroxy-3-(4-methoxyphenyl)benzopyran-4-one,N-ethylmaleamic acid 3 and N,N-dimethylamine Acid,and increased D-glycerate,xylose 2,2-keto-isovalerate,succinic semialdehyde 2,acetol 4,bis(2-hydroxypropyl)amine 2,paclitaxel 2,?-glutamic acid 1,3,5-dihydroxyphenylglycine 1,N-(2-hydroxyethyl)-iminodiacetic acid 1 and farnesaldehyde.Subsequent metabolic pathway analysis found that LBP intervention may regulate vitamin B6 metabolism,D-glutamine and D-glutamate metabolism,glycine,serine and threonine metabolism,alanine,aspartic acid and glutamate metabolism,pentose phosphate pathway,butyrate metabolism,glyoxylic acid and dicarboxylic acid metabolism,pyruvate metabolism,arachidonic acid metabolism and glycolysis or glycogen production5.The influence of lycium barbarum polysaccharides on insulin-induced HepG2 cell linesIn our human study we found that LBP intervention reduced the blood glucose levels and according to the results from metabolic pathway analysis the potential hypoglycemic mechanism may be related to the regulation of D-glutamine and D-glutamate metabolism Deterioration of glucose homeostasis during the development of diabetes will eventually affect hepatic glycogen homeostasis.Unbalanced hepatic glycogen metabolism accelerates the output of hepatic glucose ad further aggravates hyperglycemia in the peripheral circulation.In the present study,we used insulin-induced HepG2 cell lines to observe the effects of different doses(300ug/ml,75ug/ml,18.75 ug/ml)of LBP on glycogen synthesis and amino acid metabolism enzymes.We found that different doses of LBP can increase the protein level of glycogen synthase in insulin-induced HepG2 cells with the dose-response relationship.LBP inhibited the RNA expression of GLS2 protein levels.Based on the results of the study,it indicates that LBP inhibited the GLS2 protein levels and thus promoted the metabolism of glutamine,then promoted the protein expression of glycogen synthase,and finally affected the synthesis of glycogen and decreased the blood glucose levelConclusions:1.Bibliometric analysis showed that the increasingly trend of Goji berry publications from 2000 to 2018.The leading study fields were chemistry,biochemistry molecular biology and agriculture worldwide.More biochemistry molecular biology and functional studies are warranted in future.The relationship between Lycium barbarum polysaccharides intervention and diabetes is the research hot area recently2.Dietary LBP supplementation decreased the TG/HDL index significantly in healthy male.D-talose decreased,phosphate and leucine increased significantly in serum.4-Hydroxymandelonitrile 1 increased,and tyrosine 1,3-Aminoisobutyric acid 1,threitol and ribose decreased significantly in urine.Eight metabolites were simultaneously assessed by indicating the glycerophospholipid metabolism and tyrosine metabolism after LBP supplementation in males3.Amino acid metabolism was disturbed for T2D patients with/without obesity or hyperlipidemia mainly including D-glutamine and D-glutamate metabolism,taurine and hypotaurine metabolism,beta-alanine metabolism,alanine,aspartate and glutamate metabolism,arginine and proline metabolism,glyoxylate and dicarboxylate metabolism and glycine,serine and threonine metabolism,and glycine,serine and threonine metabolism.In addition,the potential mechanism for obesity and hyperlipidemia in T2D patients was explored as well,which indicates that beta-alanine metabolism,glycine,serine and threonine,arginine and proline,and pyruvate metabolism may be involved in the T2D patients with obesity or hyperlipidemia compared with T2D patients.Overall,obesity and hyperlipidemia may aggravate the progression of T2D4.Intake of 300mg/d LBP for 3 months can reduce fasting blood glucose levels in T2D patients,which may be related to increasing serum IGFBP levels,influencing vitamin B6 metabolism,amino acid metabolism and glycolysis5.LBP can inhibit the expression of GLS2 protein and promote the expression of GS protein,which may ultimately reduce blood glucose by affecting glycogen synthesis. |
PDF Full Text Request