6-Shogoal Improves Insulin Resistance In Liver Of Aged Rats

Objective To investigate the effects and mechanisms of 6-shogaol on aged-related insulin resistance（IR）in liver of rats.Methods The related gene targets of 6-shogaol and IR were identified by network pharmacology.Genes highly related to both were screened out to construct 6-shogaol---IR gene regulatory network,then verify the docking of 6-shogaol and the key target protein by the molecular docking technology.The 20-month-old male SD rats were divided randomly into the model control group（n=9）,the rats supplemented with 6-shogaol at 0.5 mg/kg（n=8）;Male SD rats（3 months old）was used as a normal control group.The expression levels of related genes and proteins were analyzed by RT-PCR and Western Blot.Results The targets of 6-shogaol were closely related to IR genes,and genes highly correlated with both mainly involved in the PI3K/AKT signaling pathway.0.5 mg/kg 6-shogaol treatment could increase the IRS1,PI3 K and AKT m RNA expression in model control rats.Compared with the normal control group,the expression of p-IRS1,total CD36 and cell membrane CD36 in the liver of the model control rats group was significantly increased,and the expression of p-AKT,GLUT2 and cytoplasma CD36 was significantly reduced.0.5 mg/kg 6-shogaol treatment significantly reversed the expression of these proteins.Conclusion 6-shogaol can improve IR in the liver of aged rats,which may be related to inhibiting IRS1（ser307）phosphorylation,promoting AKT（ser473）phosphorylation,inhibiting cell membrane CD36 expression and regulating its plasma-membrane translocation,and up-regulating GLUT2 expression.Objective: To observe the improvement effect of Modified Xiaochaihu Decoction on hypertriglyceridemia induced by high fructose in rats,and to explore its potential mechanism.Methods: 20 male SD rats were divided into 3 groups including control group（NC,n=6,free drinking water）,fructose model group（Fru,n=7,fructose water）and Modified Xiao Chaihu Decoction group（MXD,10.8g· kg-1,n=7,Fru group isocaloric fructose water）.The experiment lasted for 5 weeks.Indexes of lipid homeostasis were determined enzymatically or histologically.The expression levels of related genes and proteins were analyzed by real-time PCR and Western blot.Results: MXD treatment significantly reversed the increase of plasma TG in fructose-fed rats.Mechanismically,MXD treatment had no effect on the increase in hepatic FGF21 m RNA and protein,but significantly reversed the decrease in eWAT FGF21 m RNA and protein in furctose-fed rats.There is no change with AMPK in both m RNA and protein levels between three groups.However,MXD treatment significantly upregulated the expression of m RNA and proteins SIRT1,P-AMPK^（Thr172）,PGC1α in the liver and eWAT of fructose-fed rats.Conclusion: Modified Xiaochaihu Decoction may improve fructose-induced hypertriglyceridemia in rats,which may be related to regulating FGF21/SIRT1/AMPK/PGC1 a signaling pathway in the liver and eWAT.