| Objective:To establish a process for enrichment of gingerol parts.To observe the warming role of gingerol of ginger,dried ginger,and roasted ginger in model rats with deficiency-cold in spleen and stomach.On the basis of pharmacodynamics,the drug metabolism of three kinds gingers in model rats with deficiency-cold in spleen and stomach and the relationship between tissue distribution and menopause was studied.Methods:① Take gingerol content as the index,through the investigation of the maximum sample volume,the optimum sample concentration,eluent concentration,eluent volume,elution velocity and other parameters on D-101 macroporous adsorption resin,screen purification process of gingerol to determine the best purification and separation process of gingerol.②The warming role of gingerol in rats of deficiency-cold in spleen and stomach model:SPF male SD rats were fed for one week,were randomly divided into normal group,model group,positive group,gingerol from ginger high dose group(200mg·kg-1),low dose group(100mg·kg-1),gingerol from dried ginger high(400mg · kg-1,low dose group(200mg·kg-1),gingerol from roasted ginger high(400mg ·kg-1),low dose group(200mg·kg-1).The all is of 9 groups,10 rats in each group.In addition to the normal group,the other groups were administered to 4 DEG 1mL/100g(total acidity of vinegar is greater than or equal to 4g/100mL)continuous preparation of 10d rat model of deficiency-cold in spleen and stomach,the afternoon of the fifth day began to give medicine.Positive group were given Fuzilizhong pill suspension 6.0g·kg-1,the rest of the drugs were given with different doses gingerol suspension.The change of appearance and behavior of the rats were observed during administration,and the second,fourth,sixth,eight,ten days of food intake,water intake,body weight change,organ coefficient,gastric emptying rate and serum gastrin and motilin levels in the measured value were compared.Process the measured data using SPSS22.0 software,and evaluate temperature effect of rats with deficiency-cold in the spleen and stomach.③Drug metabolism of gingerol site in rats with deficiency-cold in the spleen and stomach:SPF male SD rats were fed for one week,randomly divided into ginger,dried ginger,and roasted ginger high dose group.On the eleventh day,rats after administration after intragastric administration of 5min,10min,20min,30min,40min,60min,90min,120min,180min,240min,360min and 480min,blood were collected from eyelid venous plexus UPLC-MS/MS was used to measure the blood drug concentration at each time point.DAS software was used to process the data to obtain pharmacokinetic parameters.The significance of each parameter was analyzed and the drug metabolism was studied①The distribution of gingerol in the deficiency-cold in the spleen and stomach model rats:The gingerol of ginger,dried ginger and roasted ginger high dose group rats were taken blood from the abdominal aorta after administration of 5min,10min,20min,30min,40min,60min,90min,120min,180min,240min,360min,480min,,immediately collected heart,liver and spleen,lung,kidney,stomach,large intestine,small intestine.A UPLC-MS method was used in combination to compare UPLC-MS patterns of ginger glucocorticoids in various tissues of rats to determine the content of effective substances in rat tissues.Test data to get the pharmacokinetic parameters by using DAS2.0 software,through the comparison of each index component in the high dose group rats in each organ of the earliest detection time,concentration,duration of enrichment of gingerol site in the case of spleen deficiency rats in vivo tissue distribution and meridian,and ginger,dried ginger,roasted ginger,comparethe differences in the distribution of rat tissue and spleen and stomach meridian.Results:①the optimum conditions of gingerol enrichment process is that the best sample concentration was 0.5g·mL-1,the sample volume is 4BV,1 static 0.5h,followed by 3BV of deionized water and 50%ethanol to remove impurities,2BV·h-1rate of 70%ethanol and 95%ethanol elution.The eluent concentration,freezing and drying to obtain black grease semi solid material.The black fat like semisolid substance was obtained by the UV spectrophotometer.UV Spectrophotometry of ginger was 82.76%,the yield is 0.33%,ginger content is 87.07%,the yield was 4.52%,ginger gingerol content is 85.87%,the yield was 4.31%.② The warming effect on the part of gingerol of deficiency-cold in the spleen and stomach rat model compared with the model group,ginger,dried ginger and roasted ginger in the high and low dose of gingerol suspension significantly improved spleen deficiency rat model of appearance,increased the amount of water and food intake and weight value significantly;improved the gastric emptying rate of rats significantly;the liver index,spleen index and thymus index were significantly increased;the serum GAS,MTL values were increased significantly(P<0.05 or P<0.01).That warming role of gingerol.is therefore explained.③ The measured group peak and the internal standard peak were only detected in the plasma samples after the drug delivery,and were not detected in the blank plasma samples,and the specificity was good.In rat plasma 6-gingerol concentration in 1.853-500ng·mL-1 from 5.00 to 200.00 ng·ml-1(R2＝0.9975);8-gingerol concentration in 1.853-500ng·mL-1 from 5.00 to 200.00ng·ml-1(R2=0.9972);10 gingerol concentration in 7.81-500ng ·mL-1 from5.00to200.00ng-ml-1(R2＝0.9952);10 gingerol concentration in ginger ketone 3.95-500ng·mL-1 from 5.00 to 200.00ng·ml-1(R2=0.9985).The intra day precision(relative standard deviation,RSD)were less than 15%,accuracy between 1.07%and 15.21%,under the condition of 4 DEG C to place 24h and freeze-thaw stability of three is good,accord with the demands of biological samples analysis guidelines.The rats in the spleen-stomach asthenia model rats were intragastrically administered with different gingerol fractions.The area under the plasma plasma concentration curve of 6-gingerol,8-gingerol,10-gingerol,and zingerone was the AUCO-t.The ginger gingerol AUC0-t is 6-gingerol>Zingerone>8-gingerol,followed by dried ginger gingerol AUC0-t:Zingerone>8-gingerol>6-gingerol;roasted ginger gingerols AUC0-t:8-glycerol>zingerone>and 6-gingerol in this order.4.Deficiency-cold in the spleen and stomach rat model in vivo distribution results showed that:in the spleen deficiency rat model,comparison of gingerol from ginger parts of 6-gingerol pharmacokinetic parameters of AUCO-t in different tissues of size:stomach>small intestine>large intestine>lung>liver>kidney>spleen>heart;8-gingerol in different tissuesofAUCO-t size:stomach>large intestine>small intestine>lung>liver>heart>spleen>kidney;10-gingerol in different tissues of AUCO-t size:stomach>largei ntestine>small intestine>lung＝heart＝liver=spleen＝kidn ey;zingerone in different tissues of AUCO-t size:stomach>large intestine>small intestine>lung=spleen>liver=heart =kidney.Deficiency-cold in the spleen and stomach rat model,comparison of ginger oleoresin ginger parts of 6-gingerol in different tissues AUC0-t size:stomach>liver>large intestine ＝kidney = spleen>small intestine>heart;8-gingerol in different tissues,the AUCO-t size of the stomach>large intestine>small intestine=lung=liver=spleen>heart>kidney;10-gingerol in different tissues of stomach intestine AUC0-t size:stomach>small intestine>large intestine>lung＝liver>heart>kidney>spleen;ginger ketone in different tissues of stomach intestine AUCO-t size:stomach>small intestine>large intestine>liver>lung>kidney>heart=spleen.In the spleen deficiency rat model,comparison of ginger oleoresin ginger parts of 6-gingerol in different tissues of stomach intestine AUCO-tsize:stomach>smallintestine>largeintestine>liver=spleen=lung>heart>kidney;8-gingerol:stomach>smallintestine>largeintestine=heart=spleen=li ver=lung= kidney;10-gingerol in the size of AUC0-t in different tissues:stomach>small intestine>large intestine>liver>lung=spleen>heart=kidney;ginger ketone in different tissues of stomach intestine AUC0-t size:stomach>small intestine>large intestine>liver= lung=spleen>heart=kidney.Conclusion:The pharmacodynamics experiment showed that the gingerol site has obvious effects on temperature,the plasma drug concentration in plasma was determined by 6-gingerol,8-gingerol,10-gingerol and ginger ketone by spleen deficiency model rats administered after blood concentration parameters,first studied the dynamic behavior in rats the body of medicine.These studies enrich the pharmacokinetic data of 6-gingiteol,8-gingiteol,10-gingiteol and Zingiber,and provide a reference for further clinical pharmacokinetics research.The four components of each organ in the spleen-stomach asthenia model rats may be distributed in various organs such as heart,liver,spleen,lung,kidney,stomach,large intestine,small intestine,etc.The earliest detection time,maintenance time,and enrichment concentration in each organ tissue showed that the distribution of gingerol in the spleen-and stomach-deficiency group was mainly concentrated in the stomach,small intestine,large intestine,and lung tissues.This distribution is the same as the traditional understanding of channel tropism of ginger. |
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