| With the advancement of urbanization,there have arisen a series of bad habits,such as high-calorie diet and inactivity,along with convenient and well-off lifestyle,which have contributed to the spread of chronic diseases worldwide[1-2]The increasing morbidity and mortality of diabetes mellitus have brought about heavy medical and economic burden to every country and region.At present,various effective hypoglycemic drugs applied clinically,cannot work well as diseases deteriorates.It's time to develop a more effective hypoglycemic drugs.Currently,people have come to be aware of the significance of health,and tend to adopt healthy therapies to prevent and treat diseases such as sports and healthy diet.And tea,as a daily drink,has become one of important way to prevent chronic diseases.The Coreopsis tinctoria Nutt.belongs to the genus Asteraceae,and its head flowers are usually used as tea drinks in the folk,in order to improve diseases such as hypertension,hyperlipemia,diabetes mellitus,etc.However,its pharmacodynamic basis and mechanisms are still unclear.Previously,our team has found that C.tinctoria tea could significantly improve the insulin resistance in the rat model induced by high-fat diets;and its total extract could significantly improve insulin resistance in HepG2 cell treated with high glucose;all those results showed that C.tinctoria has a good prevention of insulin resistance.It's well-known that insulin resistance is the main pathological basis of diabetes mellitus,so it is essential to conduct a further study that C.tinctoria has a therapeutic effect on diabetes,and provide its quality control standards.Firstly,we established a quality control method for the total flavonoids of C.tinctoria by UPLC-DAD,including 9 flavonoids((R/S)-flavanomarein,quercetagetin-7-O-?-D-glucoside,isookanin,quercetin-7-O-glucoside,marein,butein-4-O-?-D-glucopyranoside,okanin,eriodictyol and butein)and one phenylpropanoids compound(linocinnamarin).Provide reference for the quality control of C.tinctoria.Secondly,we used two kinds of diabetic animal models to evaluate the pharmacodynamics of the effect of the total flavonoids of C.tinctoria on diabetes mellitus.(1)The first one is rat model induced by streptozocin(STZ)and high-fat diet.The results showed that the high-dose CT group could significantly decrease serum GLU,TG and NEFA level,increase HDL lever,and improve impaired glucose tolerance and insulin tolerance.(2)The second one is db/db mice.The results showed that CT could significantly decrease the levels of blood lipids(TG,LDL,CHO)and improve insulin resistance(decrease GLU,HOMA-IR,PG,INS and increase ISI),and the effect of low-dose CT group has a much more effective function than medium and high-dose CT groups.The liver's steatosis was significantly improved compared with the model group,and the islets were obviously proliferated,suggesting an increase in islet secretion function.The results of the above two animal experiments show that the CT have an auxiliary therapeutic effect on diabetes mellitus,and have the potential to develop into auxiliary hypoglycemic drugs.Thereafter,transcriptomics analysis was applied to study the potential key targets regulated by CT in improving diabetes mellitus.db/db mice were conducted transcriptome analysis by RNA-seq technology.The results showed that a large number of differential expressed genes were found by comparing CT vs.Model and Model vs.Control.The GO function annotation and KEGG enrichment pathway analysis on these differential expressed genes,revealed that they were mainly involved in multiple biological processes such as energy metabolism,glucose metabolism,lipid metabolism,etc.,and multiple pathways related to diabetes such as citrate cycle,pentose phosphate pathway,glycolysis/gluconeogenesis and so on,suggesting C.tinctoria were characteristized by multi-level regulation on diabetes mellitus.According to the results of GO and KEGG enrichment analysis,11 genes were selected for real-time fluorescence quantitative PCR(qPCR)verification.It was found that the C.tinctoria could regulate Slc2a2,Cd36,Fabp4,Prkca,Ugtla5,Slc27a4,Pygl,Aldob,Ogt,Pik3c2b and Sdhb to improve diabetes mellitus.And the experimental results are basically consistent with the results of RNA-seq sequencing.Finally,208 targets were found through virtual screening and were mainly related to diseases such as cancer,cardiovascular disease,neurological disease and glycolipid metabolistic disease.And 15 potential targets and 20 active compounds(including 19 flavonoids and one phenylpropanoid)were viewed as key targets and active compounds of CT,involving in metabolic pathways such as hormone regulation,anti-inflammatory,anti-oxidation,insulin resistance,energy metabolism,etc.And it turned out that C.tinctoria has the potential to treat cancers,cardiovascular diseases,neurological diseases and glycolipid metabolism disorders,and has the potential for further development.In conclusion,the above research results systematically evaluated the pharmacological activity of C.tinctoria and provided a direction and reliable basis for the following mechanism exploration of C.tinctoria. |
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