Study On The Hypoglycemic Effect And Mechanism Of Malonyl Ginsenosides From American Ginseng Flower In T2DM Mice

Diabetes is one of the most serious chronic endocrine disorder.The prevalence of diabetes has been steadily increasing over the past few decades.T2DM is a disorder of glucose and lipid metabolism characterized by induced hyperglycemia,hyperlipidemia and insulin resistance.Some synthetic drugs have been widely used in the management of T2DM,but these medications have been found to cause variable side effects,including endocrine disorders and gastrointestinal dysfunction.Therefore,the development of novel,safe and effective natural compounds to prevent or treat T2DM is critically important.Ginsenosides are considered to be the main functional ingredients of the American ginseng flower,including neutral ginsenosides（Re,Rb₁,Rb₂,Rb₃,Rc,Rd and Rg₁）and malonyl ginsenosides（MRb₁,MRb₂,MRb₃,MRc and MRd）.The neutral ginsenosides have also been reported extensively with wide pharmacological.Malonyl ginsenosides are acidic and high polarity.It is very unstable and can degrade into corresponding neutral ginsenosides.Because of malonyl ginsenosides are more difficult to isolation and evaluation,the composition and bioactivities of malonyl ginsenosides were underestimated.In the present study,isolation and characterization of malonyl ginsenosides from American ginseng flower were studied.The effects of AGF-MGR on hyperglycemia and hyperlipemia of type 2 diabetic mice,and the related mechanisms of action were also explored.This experiment uses a large number of conventional natural product chemical techniques,mainly including:organic solvent extraction,macroporous resin column chromatography,ODS column chromatography,combined with HPLC separation technology,4 compounds（MRb₁,MRb₂,MRb₃,MRc）were isolated and identified from American ginseng flower.This experiment to study the therapeutic effect of AGF-MGR on T2DM mice by used of STZ combined with high-fat diet induced mouse model of T2DM mice.Our results showed that AGF-MGR treatment significantly reduced fasting blood glucose and improved glucose tolerance insulin resistance and liver damage.Meanwhile,AGF-MGR has significant effects on hyperlipidemia caused by metabolic disorder in T2DM.TC and TG levels were reduced by 42.8%（P<0.01）and 39.4%（P<0.001）,respectively.Further,Western blot analysis revealed that the anti-hyperglycemic activity of AGF-MGR was related to the activation of the IRS1/PI3K/Akt and GLUT4 signaling pathway.The activation of the AMPK/ACC signaling pathway might be responsible for its hypolipidemic effect.