The Hypoglycemic Effects Of Ginsenoside F2

Diabetes is a global epidemic chronic disease and one of the biggest health challenges facing modernization.In recent years,natural products such as saponins,flavonoids,polysaccharides,polyphenols have been proven to possess hypoglycemic activity with low side effects in vivo and in vitro,which have a positive effect on insulin resistance and diabetes symptoms.Ginseng is a kind of medicinal and edible plant.The main active ginsenoside have been used as an adjuvant to treat diabetes for many years.Experimental and clinical data indicate that the anti-diabetic effects of ginsenosides was closed with their antioxidant,anti-inflammatory and anti-hyperglycemic activities.Ginsenosides F2(GF2)is a low-sugar-based saponin with biological activities such as antioxidant,anti-inflammatory,anti-cancer,and lipid-lowering.Its hypoglycemic effect and related mechanisms are still unclear.Therefore,this work firstly predicts the hypoglycemic effect and potential mechanism of GF2 through network pharmacology.Furthermore,the in vitro insulin resistance model was established to study its hypoglycemic activity and molecular mechanism.The main research contents are as follows:(1)Potential hypoglycemic targets of GF2 was analyze through network pharmacology,and 26 related targets such as IL2,STAT3,AKT1,AKT2,and AKT3 was obtained.The 26 targets were analyzed by GO function annotation and KEGG pathway enrichment analysis.GO function annotation divides the functions of these26 target genes into three parts,biological processes,molecular functions,and cellular components,which mainly involved in biological processes such as metabolism,regulation,stress,catalysis.Moreover,148 related pathways were enriched by KEGG pathway.The following such as AMPK,MAPK,PI3K/AKT and insulin signaling pathway was closed related with hypoglycemia.(2)The insulin resistance model of human liver(HepG2)cells was stimulated by high glucose.The antoxidant effect of GF2 on IR-HepG2 cells and the PI3K/AKT/GSK-3β signaling pathway were studied.HepG2 cells were stimulated by55 m M glucose for 24 h,and the insulin resistance model was successfully established,which was stable within 36 h.The cell viability results showed that GF2 had no effect on the viability of HepG2 cells and IR-HepG2 cells within 50 μM.The 2-NBDG uptake experiment showed that GF2 had a promoting effect on IR-HepG2 cell glucose absorption and had an in vitro hypoglycemic activity.High glucose induction can cause cells to produce a large amount of ROS,activate MAPK signaling pathway and cause oxidative stress to increase insulin resistance.GF2 reduces oxidative stress through the inhibition of phosphorylation of JNK,ERK1/2 and p38 MAPK in the MAPK pathway,reduction of the levels of ROS and MDA,improves and increasing the SOD activity.The expression levels of genes and proteins related to glucose metabolism were detected by RT-q PCR and Western blot.The results showed that GF2 can activate the PI3K/AKT signaling pathway,up-regulate the levels of GLUT-2and GLUT-4 in IR-HepG2 cells,and promote the absorption of glucose.At the same time,GF2 reduces the expression level of PEPCK and G6 Pase and inhibits gluconeogenesis.These results indicate that GF2 may reduce cellular oxidative stress in IR-HepG2 cells through the MAPK signaling pathway,participate in the PI3K/AKT/GSK-3β signaling pathway,promote glycogen synthesis,inhibit gluconeogenesis,and improve glucose metabolism disorders.(3)The "cocktail" method was used to establish in vitro insulin resistance3T3-L1 adipocyte model and explore the effect of GF2 on IR-3T3-L1 based on the PI3K/AKT signaling pathway.Dexamethasone as a positive control can inhibit the expression of IRS-1 and GLUT-4.3T3-L1 adipocytes were treated with 1 μM dexamethasone for 48 h can successfully establish an IR model.RT-q PCR and western blot results revealed that the expression of IRS-1,GLUT-1 and GLUT-4genes in the model group was inhibited,the expression levels of p-PI3 K,p-AKT and AKT proteins decreased,and glucose absorption was inhibited.Compared with the model group,GF2 up-regulated the expression levels of IRS-1,GLUT-1,and GLUT-4genes.It also promoted the expression levels of p-PI3 K,p-AKT,and AKt,and promoted cellular sugar absorption.These results showed that GF2 promotes the sugar absorption of IR-3T3-L1 adipocytes by activating the PI3K/AKT signaling pathway.The hypoglycemic mechanism of GF2 in HepG2 cells was further verified.The results of this study indicate that the hypoglycemic mechanism of GF2 may be realized through PI3K/AKT pathway.