| Magnolia is a dry bark,dry skin or root bark of Magnolia officinalis Rehd.et Wils.or Magnolia officinalis subsp.biloba Rehd.et Mils.,Cheng et Law.Magnolia is a traditional aromatized damp medicine,which is bitter,spicy and warm.It has the functions of stagnation of dampness and tempering.According to the "Shen Nong's Herbal Classic" records,Magnolia is responsible for food stagnation,abdominal distension,constipation,wet resistance in the coke,vomiting and vomiting,suffocating,chest full of asthma.Modern pharmacological studies have shown that Magnolia has antibacterial,anti-inflammatory,anti-viral,anti-allergic,affecting gastrointestinal activities,muscle relaxation and central inhibition.Its main chemical composition is more than 80 kinds of volatile oil components,mainly containing ?-eudesmol.Neolignan phenolic components,account for about 5%of the total amount of medicinal materials,including more than 20 kinds of which,like magnolol,honokiol,isomagnolol,tetrahydromagnolol,etc,and 9 kinds of alkaloids,resin components and a small amount of saponins,etc.Magnolia is an important drug for the treatment of metabolic diseases.However,at present,there is no research report on the basis of Magnolia in the treatment of metabolic diseases.The pharmacodynamic basis and mechanism of action of Magnolia in the treatment of metabolic diseases are still unclear.Traditional Chinese medicine(TCM)mainly uses Magnolia to treat chest and abdomen full of suffocation,pain relief,stomach and qi.The simple stomach and moistening of the stomach and the TCM from the spleen deficiency and dampness treatment of type 2 diabetes is very consistent,but the specific mechanism and pharmacodynamic basis of it is completely unknown.This paper will use the theory above that TCM treating type 2 diabetes from spleen deficiency and phlegm dampness,to study in deed the pharmacodynamics of hypoglycemic drugs and their substance bases.Under the guidance of the above-mentioned TCM theory,this paper selected the traditional aromatic spleen and dampness medicine,Magnolia,as the research object,to conduct the in-depth research on its hypoglycemic effect and its pharmacodynamic substance basis.The results showed that Magnolol which is the main component of Magnolia,had a very significant hypoglycemic effect,and the mechanism of its efficacy was the partial activation of peroxisome proliferator-activated receptors(PPARs).PPARs are nuclear receptors superfamily ligand-dependent activated nuclear transcription factors.Three subtypes of ?,?/? and y have been found.PPARs have been shown to play a regulatory role in many pathophysiological processes,such as sugar, lipid and cholesterol metabolism,and PPARs are key targets for the treatment of human metabolic diseases.Due to the currently used insulin sensitizers are exclusively and completely agonistic of PPAR ? receptors,they have a serious adverse reaction such as weight gain and heart failure while exerting therapeutic effects on type 2 diabetes. PPARa,? bis and/or PPARa,y,8 three-target partial agonists can overcome this limitation,so the search for PPAR dual and/or three target partial agonists has become a research hotspot in this field.In the previous stage of virtual screening and actual screening at the molecular level,the natural molecules of Magnolia lignans were PPARa,y-and/or PPARa,y,8 three-target agonists,and the neolignans in Magnolia officinalis.In this paper,the components of neolignans in Magnolia officinalis were systematically separated,and the mechanism and structure-activity relationship were explored,so as to verify its efficacy from the molecular,cellular and overall animal level,providing a basis for the discovery of a new type of insulin sensitizer with excellent performance and elucidation of the material basis of Magnolia officinalis for the treatment of metabolic diseases.Therefore,this paper optimized the extraction process of Magnolia,and prepares high-purity honokiol and the compatibility of water- soluble cellulose of coix seed with honokiol was preliminarily proved.The effect of honokiol on glucose and lipid metabolism in type 2 diabetic mice was examined from the overall animal level using the type 2 diabetes KK/Upj-AY mouse model.Through the STZ1 type diabetes model,it was demonstrated that honokiol has a significant effect on lowering the blood glucose level of STZ1 type diabetic rats.The main contents include the following parts:Taking the content of honokiol as the index,the optimum process parameters for the extraction of honokiol were optimized by three-factor four-level orthogonal test method:8 times the amount of 80%ethanol,extracted 3 times,each extraction 2 h.The combination of column chromatography and recrystallization technology was used to systematically study the refining process of magnolol.The preparation process of honokiol was established,and more than 95%of honokiol monomer was isolated.The molecular structure was identified by NMR spectroscopy.The extraction process is optimized by orthogonal test,and the concentrated liquid is combined three times.The obtained extract is used to recover the solvent under reduced pressure to a relative density of 1.10(50?).and 10 times of water is added to the concentrated extract,and the mixture is thoroughly stirred and discarded.The aqueous solution was added to the extract by adding 10 times of 95%ethanol,fully dissolved,95%ethanol solution was collected,the residue was discarded,and the 95%ethanol solution was concentrated to dryness under reduced pressure,and extracted with 50%ethanol three times.The 50%ethanol extract was collected,concentrated to dryness under reduced pressure,and the residue was recrystallized to yield the monomer of honokiol.The orthogonal test was designed to optimize the optimal extraction process parameters of water-soluble cellulose to 25 times the amount of raw water,and extract it by heating and refluxing for 3 times for 5 h each time.Through the formulation study of the preparation of Heyi Capsule,the preparation process of honokiol and coix seed was established as follows:honokiol was heated on a water bath at 90? until the magnolol was completely dissolved,and the pulverization of water-soluble cellulose of coix seed was carried out to 80-100 mesh,added to the dissolved honokiol,stirred well and cooled to room temperature.An animal model of type 2 diabetes was established using an internationally recognized spontaneous KK/Upj-Ay diabetic mouse,and the model was used to evaluate the in vivo efficacy of honokiol.To study the hypoglycemic effect of honokiol on type 2 diabetes KK/Upj-AY mice,the changes of blood lipids and the effects on islets,epididymal fat and liver tissues.The KK/Upj-AY mice were given high-fat diet to produce a type 2 diabetes model.The rats were administered by intragastric administration for 35 days,and the differences of the corresponding detection indexes and pathological sections of the pancreas were observed.Compared with the normal group,the blood glucose level of the model group was significantly increased(P<0.01),and the AUC(Area Under Curve)value of the model group was significantly increased(P<0.01).The expression level of insulin was significantly increased(P<0.01).The serum levels of total cholesterol(TC),total triglyceride(TG)and low density lipoprotein(LDL)in the model group.The content of the mice was significantly increased(P<0.01),and the body mass of the model group was significantly increased from the 0th week(P<0.01).Compared with the model group,the blood glucose levels of the honokiol high-dose group and the honokiol medium-dose group were significantly lower(P<0.01,<0.05).The AUC values of the high-dose honokiol and low-dose honokiol groups were significantly lower(P<0.01,P<0.05).Serum insulin expression levels were significantly lower in the high dose group of honokiol and the honokiol medium dose group(P<0.01).Serum TC levels were significantly lower in the low-dose honokiol group,the honokiol medium-dose group,and the honokiol high-dose group(P<0.01).Serum TG levels in the low dose group of honokiol and honokiol medium dose group were significantly decreased(P<0.01,P<0.05).The content of serum low density lipoprotein(LDL)of the mice in the middle dose group of honokiol was significntly decreased(P<0.05).The serum high density lipoprotein(HDL)content in the high dose group of honokiol was significantly increased(P<0.05).The body weight of the mice in the high dose group of magnolol was significantly decreased from the second week(P<0.01).It was proved that honokiol had the effect of lowering the blood glucose level of type 2 diabetes KK/Upj-AY mice,and also had the effect of improving insulin resistance caused by dyslipidemia,and did not induce an increase in body weight of mice.Especially by comparing the body quality,and the determination of lipid levels,prove honokiol in animal blood glucose significantly reduce the model at the same time,can significantly reduce weight,animal models with significantly lower the levels of total cholesterol,triglyceride,LDL,increase the levels of HDL,so as to realize synchronous adjustment of glycolipids,avoiding the exclusive agonist rosiglitazone and PPARy PPAR exclusive agonist insulin sensitizer is the weight gain of edema,heart failure and a series of serious adverse reactions. |
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