| Diabetes is an endocrine metabolic disease caused by relative inadequate insulinsecretion or absolute lack of it. Diabetes, together with the cancer and cardiovascular disease,are known as the world's three major diseases harming people's health. World HealthOrganization predicts that the number of people with diabetes will double by 2025 and it isexpected to exceed 300 million. And the number of Chinese diabete patients ranks the secondin the world. Expect insulin, other drugs such as biguanides, sulfonylureas, alpha-glucosidaseinhibitor, thiazolidine Diketone (insulin sensitizers), fennel acid chloride (insulin secretingagents) and oral hypoglycemic agents are usually being used to teat diabetes. However, allthese western medicine have some limitations and side effects.Chinese traditional medicineare more suitable for long-term control of diabetes due to the advantages of more safety andless side effects. Mulberry leaves had been used to treat diabetes even since ancient time, andmodern researches also have proved that mulberry leaves can help lower blood glucose andlipid, scavenge free oxygen radicals and have anti-inflammatory and antiviral effects.Alkaloids, flavonoids and other component coming from mulberry leaves all haveα-glucosidase inhibitory activity.An effective measure to treat diabetes is to control blood sugar. One of the main sourcesof blood sugar is from carbohydrates'digestion and absorption in intestinal. Carbohydratesare broken down into monosaccharides that can be absorbed byα-glucosidase and thentransported into the blood circulation through the help of intestinal transporters. So,α-glucosidase, sodium-glucose cotransport 1(SGLT1), facilitated diffusion of glucosetransporter 2 (GLUT2) and Na~+-K~+-ATP enzyme are involved during the absorption processof intestinal glucose.Research on extracting hypoglycemic component from mulberry leaves and studying themechanisms has significant practical value and also can broad the application prospects, thenof course will lay a solid theoretical basis for the future research of traditional Chinesemedicine on treating diabetes.In this article, mulberry leaf extracts, which contain alkaloids,polysaccharide and flavones active components, were used to explore the possible mechanismof Mulberry leaf extracts on lowering blood sugar from the glucose's generation and glucosetransport. The mulberry leaf extracts were donated by Chengdu Institute of Biology, ChineseAcademy of Sciences.Firstly, an optimum system was established to study theα-glucosidase inhibitory activity in vitro through the single factor and factorial design experiments on substrate concentration,the amount of enzymes and reaction time . On that basis, the effect of mulberry leaves extractsonα-glucosidase inhibitory and kinetics of enzyme inhibition were studied. Meanwhile,further study on different sources ofα-glucosidase's inhibition activity was investigated byusing human colon aden carcinoma cell Caco-2. The results showed that the best reactionsystem ofα-glucosidase inhibitory activity in vitro was as followed: sugar substrateconcentration is 40 mg·mL-1, amount of enzyme is 0.2 mL and reaction time is 25 min ;Mulberry leaves extracts hadα-glucosidase inhibitory effect on both deriving from yeast andCaco-2 cell source and the inhibition modle was mixed competitive inhibition, which isdifferent from the positive control of non-competitive inhibition.Secondly, effects of mulberry leaves extracts on Na~+-K~+-ATPase, SGLT1 and GLUT2mRNA expression in intestinal were discussed using natural differentiated Caco-2 cells. Theresults showed that the activity of Na~+-K~+-ATP enzymes was reduced by Mulberry leafextracts and the mRNA expression of Na~+-K~+-ATPase, SGLT1 and GLUT2 were alsoreduced.From all the research that were shown above, it can be concluded that mulberry leafextracts can reduce glucose absorption through inhibitingα-glucosidase activity；decreaseenergy supply through reducing the activity of Na~+-K~+-ATPase and effectively reducedglucose transport into the blood via controlling the gene expression of Na~+-K~+-ATPase,SGLT1 and GLUT2. As a consequence, we think the hypoglycemic effect of mulberry leafextracts is related to theα-glucosidase inhibition and the intestinal glucose transport bycontrolling the blood glucose levels through the influence of production and transport ofblood glucose. |
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