The Mechanism Of The Extract Of Moringa Oleifera Leaves Regulating The Hypothalamic Feeding Center Of ZDF Rats

ObjectiveTo study the effect of different doses of Moringa oleifera leaves alcohol extract on glycolipid metabolism and appetite suppression in ZDF rats,and to explore the mechanism of the regulation of the hypothalamus feeding center based on the insulin pathway in the hypothalamus and the expression of the downstream protein in the control of the hypothalamus.Method8 male ZL rats of 6 week old as normal control group(Nor)rats,50 male ZDF rats of 6 week old were fed for 1 weeks,the Purina 5008 induced by diet induced 4 weeks,after 4 weeks,the diabetic rats were screened according to the blood glucose level.And use the method of region group random,the rats were divided into model group(Con),western medicine group(Met),low dose group(EoM1)of Moringa oleifera leaves alcohol extract(EoM1),low dose group(EoMm)of Moringa oleifera leaves alcohol extract and low dose group(EoMh)of Moringa oleifera leaves alcohol extract,8 rats in each group.After the group was divided,the western medicine group was given the water solution of 0.18 g Kg-1.d-1 metformin,and the EoMl group was given 150 mg Kg-1·d-1 horseradish leaf alcohol extract daily,and EoMm group was given 300 mg·Kg-1·d-1 Moringa oleifera leaves alcohol extract daily.The total volume was 3 ml of each rat.Only the rats in the model group and the normal group were given the same amount of normal saline for 6 weeks.The blood glucose,body weight and food intake were monitored during the intervention.After the intervention,the rats were anesthetized and killed.Serum glucose and lipid metabolism related indicators were collected.Hypothalamus tissue was cryopreserved at-80 ℃ for PCR and WB detection.ResultsThe blood sugar,blood lipid,insulin,liver function,OGTT,AUC,serum glucoprotein and leptin in ZDF rats were significantly higher than those in ZL rats(P<0.01).From the third week of treatment,the blood sugar and weight of the treatment group were significantly lower than that of the control group.The weight gain of the four treatment groups were significantly lower than that in control group(p<0.05),and the results of OGTT and AUC were significantly lower than the control group(P<0.05),and the serum fasting insulin,serum glucoprotein and leptin in the treatment group were significantly lower than those in the control group.The HOMA steady-state model showed that the HOMA-IR in the treatment group was significantly lower than the model group,and the HOMA-IS was significantly higher than that in the model group.The results of blood lipid showed that the Moringa oleifera leaves could reduce the total cholesterol and glycerol three lipid level(P<0.05).Rat liver transaminase results suggest that Moringa oleifera leaves can reduce the liver transaminase levels in rats(P<0.05).Histological observation showed that Moringa leaves can increase the liver glycogen synthesis of ZDF rats,reduce liver fat,protect the islet cells.The results showed that the Moringa oleifera leaves and metformin significantly decreased the food intake of rats(p<0.01).The results of PCR and WB in the hypothalamus showed that Moringa oleifera leaves and metformin could increase the level of phosphorylation of IRS-PI3K-AKT-Fox01 signaling(P<0.05),decrease the expression of NPY protein(P<0.01),and increase the transcription of melanocortin receptor gene in the hypothalamus(P<0.01),and increases the transcription of orexin and thyrotropin releasing hormone(P<0.01),thereby playing an inhibitory role in appetite.Conclusion1.Moringa oleifera leaves alcohol extract can reduce the blood sugar and weight of ZDF rats,improve the insulin resistance,increase the synthesis of liver glycogen,protect the islet cells and improve the metabolism of glucose in ZDF rats.2.Moringa oleifera leaves alcohol extract can reduce the total cholesterol and triglyceride in rats,reduce the accumulation of liver fat,protect the liver and reduce liver transaminase.3.By regulating the insulin signaling pathway in the hypothalamus,Moringa oleifera leaves can increase the expression of POMC protein,reduce the protein expression of AgRP,increase the transcription of the melanin receptor gene,and then increase the transcription of the thyroid stimulating hormone releasing hormone in the hypothalamus,inhibit the gene transcription of orexin,and eventually inhibit the appetite of rats,reduce food-intake and reduce weight.