CN103585402A - Application of Dioscorea nipponica total saponins in preparation of medicines for treatment of diabetes mellitus and complications of diabetes mellitus - Google Patents
Application of Dioscorea nipponica total saponins in preparation of medicines for treatment of diabetes mellitus and complications of diabetes mellitus Download PDFInfo
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Abstract
The invention discovers that the Dioscorea nipponica total saponins have a remarkable function of improving insulin resistance, reducing blood sugar content of hyperglycemia model and increasing hepatic glycogen/muscle glycogen content of the same, and regulating glucose and lipid metabolism disorder; and the invention discloses an application of Dioscorea nipponica total saponins in preparation of medicines for treatment of diabetes mellitus and complications of the diabetes mellitus, especially an application in preparation of medicines for treatment of acute hyperglycemia, diabetes mellitus II or hereditary diabetes mellitus, and an application in preparation of medicines for treatment of diabetes mellitus induced osteoporosis or preparation of medicines for treatment of diabetes mellitus induced kidney function decrease.
Description
Technical field
The present invention relates to a kind of new purposes of Effective Component of Chinese Medicine, the application of especially a kind of Yam total saponin extracting in preparation treatment diabetes and complication medicine thereof from Rhizoma Dioscoreae Nipponicae.
Background technology
Diabetes are the metabolism disorder diseases that threaten whole mankind's health, and its course of disease is longer, as can not get for a long time good effector, is easy to merge multiple complications, and diabetic complication has almost related to each internal organs of human body, is referred to as " origin of hundreds of diseases ".Chemical synthetic drug has many deficiencies aspect treatment diabetes and complication thereof, and Chinese medicine and effective ingredient thereof have significant therapeutic effect to diabetes and complication tool thereof.
Rhizoma Dioscoreae Nipponicae be Dioscoreaceae (
dioscoreaceae) plant wear mountain Rhizoma Dioscoreae (
discorea nipponica Makino) dry rhizome, another name Dioscorea nipponica bone, Dioscorea nipponica Mak. Ningpo Yam Rhizome, Canis familiaris L. Rhizoma Dioscoreae, wear mountain bone, ground joist, string Eumeces Chinensis etc.Rhizoma Dioscoreae Nipponicae medical material feeble QI, bitter and puckery flavor, warm in nature, have relaxing muscles and tendons to promote blood circulation, an effect of the diuretic that helps digestion, eliminate the phlegm preventing the attack (or recurrence) of malaria and wind-expelling pain-stopping, is usually used in treating anemofrigid-damp arthralgia, chronic tracheitis, dyspepsia, strain is sprained and the diseases such as malaria.Yam total saponin contains the multiple natural steroid saponins compounds such as dioscin, methyl dioscin, former methyl dioscin, has the immunity of regulating, treats rheumatoid arthritis, improves cardio and vascular function, eliminates the phlegm, the multiple pharmacological effect such as antitumor.But, up to now, the research report there are no Yam total saponin at preparation treatment diabetes and complication medicine thereof.
Summary of the invention
The present invention found Yam total saponin tool be significantly improved insulin resistant, can reduce hyperglycemia model blood sugar content and increase its liver/muscle glycogen content, regulate the effect of glycolipid metabolism disorder, invented the application of a kind of Yam total saponin in preparation treatment diabetes and complication medicine thereof.
Technical solution of the present invention is: the application of a kind of Yam total saponin in preparation treatment diabetes and complication medicine thereof.
The application of described Yam total saponin in preparation treatment diabetes and complication medicine thereof is the application in preparation treatment acute hyperglycemia, type Ⅱdiabetes mellitus or heritability diabetes medicament.
The application of described Yam total saponin in preparation treatment diabetes and complication medicine thereof is medicine for treating osteoporosis or the application in the renal hypofunction medicine of preparation treatment diabetes-induced at preparation treatment diabetes-induced.
The present invention found Yam total saponin tool be significantly improved insulin resistant, can reduce hyperglycemia model blood sugar content and increase its liver/muscle glycogen content, regulate the effect of glycolipid metabolism disorder, invented the application of Yam total saponin in preparation treatment diabetes and complication medicine thereof.Especially the application in preparation treatment acute hyperglycemia, type Ⅱdiabetes mellitus or heritability diabetes medicament, and medicine for treating osteoporosis or the application in the renal hypofunction medicine of preparation treatment diabetes-induced of in preparation, treating diabetes-induced.
Accompanying drawing explanation
Fig. 1 is the pathological section figure of Yam total saponin on the impact of type Ⅱdiabetes mellitus rat liver.
Fig. 2 is the pathological section figure of Yam total saponin on the impact of db/db mouse liver.
Fig. 3 is the small animal imaging figure that diabetes rat gives Yam total saponin.
The specific embodiment
1. the effect of Yam total saponin to the sugared mice of acute height
60 of KM mices, adapt to and feed after one week, be divided at random 6 groups: blank group (i.g. 0.5% (w/v) CMC-Na), model group (i.g. 0.5% (w/v) CMC-Na), high dose group (i.g. Yam total saponin suspension (Yam total saponin is dissolved in 0.5% (w/v) CMC-Na) 300 mg/kg), middle dosage group (i.g. Yam total saponin suspension 150 mg/kg), low dose group (i.g. Yam total saponin suspension 75 mg/kg) and positive controls (i.g. glibenclamide suspension 15 mg/kg).Every day, gavage was 1 time, and gavage is 7 days continuously, gave the glucose solution (0.2 g/ml) of mice 2 g/kg after overnight fasting.Half an hour, posterior orbit was got blood, and blood, in 4 ℃ and centrifugal 10 min of 1000 g, is divided and gets serum, according to glucose assays test kit description, measured glucose in serum content; Put to death mice, take out mouse liver, according to liver/muscle glycogen, measure kit measurement glycogen content.With SPSS 11.5 softwares, data are added up, obtain table 1.
The impact of table 1 Yam total saponin on the sugared mouse blood sugar of acute height and hepatic glycogen content
Compare with model group,
*p < 0.05,
*p < 0.01.
Result shows: (300,150 and 75 mg/kg) is comparatively remarkable to the blood sugar reducing function of the acute hyperglycemia mice of glucose induction for Yam total saponin.In table, data are known, and high dose group and middle dosage group blood glucose decline respectively 18.0% and 15.0%, more more remarkable than the glibenclamide drug effect of 15 mg/kg.Meanwhile, Yam total saponin high dose group and middle dosage group can make liver/muscle glycogen of high sugared mice rise respectively 92.0% and 77.0%.
2. the effect of Yam total saponin to type Ⅱdiabetes mellitus
100 of Wistar rats, adaptability is fed 1 week, according to table of random number method, chooses at random 10 as blank group and simple administration group, gives blank Emulsion (i.p, 20 ml/kg), remaining 80 give fat milk (i.p, 20 ml/kg) as modeling group, after five weeks, water 12 h are can't help in rat fasting, the low dose of STZ(30 mg/Kg of lumbar injection), induction type Ⅱdiabetes mellitus model, injection process requires lucifuge, quick.Modeling group is cutoff fat milk, normal diet, after 7 days, fasting be can't help water 12 hours, measure its fasting glucose, using the rat of fasting glucose >=16.7 mmol/L (60) as the successful rat of modeling, and adopted table of random number to be divided into 5 groups, be respectively model group (i.g. 0.5% (w/v) CMC-Na), high dose group (i.g. Yam total saponin suspension 200 mg/kg), middle dosage group (i.g. Yam total saponin suspension 100 mg/kg), low dose group (i.g. Yam total saponin suspension 50 mg/kg) and positive controls (i.g. glibenclamide suspension 10 mg/kg).Blank group gives 0.5% (w/v) CMC-Na solution (i.g.), and simple administration group gives Yam total saponin suspension 200 mg/kg (i.g.).Meanwhile, blank group gives normal feedstuff with simple administration group, and other groups give high lipid food.After administration 8 weeks, rat vena ophthalmica clump is got blood in 4 ℃ and centrifugal 10 min of 1000 g, minute gets serum, minute gets part liver to carry out hepatic pathology assessment, the results are shown in Figure 1.
Yam total saponin does not suppress the normal growth of rat, and the rat body weight of high dose and middle dosage group is compared with model group in administration process, significantly increases.And the dietary amount of high dose Yam total saponin suspension group reduces by 35.0% than the dietary amount of diabetic model group rat, amount of drinking water reduces by 66.0%, has significantly regulated the integral energy metabolism of rat.
Oral glucose tolerance experiment:
After each treated animal administration the 50th day, carry out OGTT, be that fasting be can't help water after 12 hours, with 2 g/kg dosage gavages, give 50% glucose solution, then 0,30,60,90 and 120 min after giving glucose get blood from rat tail point respectively, full-automatic blood glucose meter is measured blood glucose value, and it the results are shown in Table 2.Result shows that the blood glucose value of each administration group rat different time points compares remarkable decline with model group, and has obvious dose dependent.
Serological index is measured:
Glycolipid metabolism index in serum, comprises glucose, TG, TC, LDL, HDL, FFA and GHb, and specific experiment operates all by test kit related description.The results are shown in Table 3.
Measurement result shows, Yam total saponin has significantly regulated glycolipid metabolism level, high dose group makes TG, TC, LDL and the FFA of diabetes rat reduce respectively 25.0%, 48.0%, 67.0% and 30.0%, and blood sugar content meansigma methods is down to 5.72 mmol/L, compares and has declined 76.0% with model group.Measure in addition the level of serum insulin, shown the shape that Yam total saponin energy diabetes-alleviating later stage insulin content declines
Condition, remains in suitable level insulin level.
Table 2 Yam total saponin is on the impact of diabetes rat glucose tolerance (comparing * * p < 0.01) with model group
Table 3 Yam total saponin is on the impact of diabetes rat serological index (comparing * p < 0.05, * * p < 0.01) with model group
3. the effect of Yam total saponin to C57BL/KsJ-db/db mice
30 of the C57BL/KsJ-db/db mices of 4 weeks left and right, are divided into model group and administration group at random, and 15 every group, blank group is 15 C57 mices.Administration group gavage gives Yam total saponin suspension (300 mg/kg), every day 1 time, successive administration 4 weeks.Blank group and administration group give 0.5% (w/v) CMC-Na solution.When experiment finishes, mouse orbit is got blood, and blood, in 4 ℃ and centrifugal 10 min of 1000 g, is divided and gets serum, and the content according to measuring test kit detail specifications mensuration glucose in serum, insulin and TG, TC, the results are shown in Table 4; Put to death mice, take out mouse liver, adopt H & E dyeing and PAS staining, liver is carried out to pathology assessment, the results are shown in accompanying drawing 2.Result shows, the blood glucose in administration group serum, insulin, TC, TG level than the remarkable reduction of model group (
p< 0.01), this shows that Yam total saponin can regulate diabetics glycolipid metabolism disorderly, thereby prevents the generation of diabetic vascular complications.
The impact of table 4 Yam total saponin on C57BL/KsJ-db/db serological index
Compare * * P < 0.01 with model group
Oral glucose tolerance experiment:
Each treated animal administration is carried out to OGTT after 4 weeks, be that fasting be can't help water after 12 hours, with 2 g/kg dosage gavages, give 50% glucose solution, then 0,30,60,90 and 120 min after giving glucose get blood from Mouse Tail-tip respectively, and full-automatic blood glucose meter is measured blood glucose value.It the results are shown in Table 5.The blood glucose value of administration group db/db mice different time points is compared remarkable decline with model group.
The impact of table 5 Yam total saponin on diabetes rat glucose tolerance
4. the therapeutical effect of the complication that Yam total saponin causes diabetes
100 of Wistar rats, adaptability is fed 1 week, according to table of random number method, chooses at random 10 as blank group and simple administration group, gives blank Emulsion (i.p, 20 ml/kg), remaining 80 give fat milk (i.p, 20 ml/kg) as modeling group, after five weeks, water 12 h are can't help in rat fasting, the low dose of STZ(30 mg/Kg of lumbar injection), induction type Ⅱdiabetes mellitus model, injection process requires lucifuge, quick.Modeling group is cutoff fat milk, normal diet, after 7 days, fasting be can't help water 12 hours, measure its fasting glucose, using the rat of fasting glucose >=16.7 mmol/L (70) as the successful rat of modeling, and adopted table of random number to be divided into 5 groups, be respectively model group (i.g. 0.5% (w/v) CMC-Na), high dose (i.g. Yam total saponin suspension 200 mg/kg), in (i.g. Yam total saponin suspension 100 mg/kg), low (i.g. Yam total saponin suspension 50 mg/kg) and positive controls (i.g. glibenclamide suspension 10 mg/kg).Blank group gives 0.5% (w/v) CMC-Na solution (i.g.), gives merely Yam total saponin suspension 200 mg/kg(i.g.).Meanwhile, blank group gives normal feedstuff with simple administration group, and other groups give high lipid food.After administration 8 weeks, collect rat urine, measure urine amount, and according to measuring content results that test kit detail specifications measures urine creatine (Urine creatinine) and blood urea nitrogen (Urine BUN) in urine in Table 6.Result shows, Yam total saponin can significantly reduce the content of urine creatine in diabetic model group rat urine, can significantly promote the content of blood urea nitrogen, makes the graft function normal level of diabetes rat.
Adopt the Whole Body Bone Scanning density of X ray bioluminescence functional examination rat and the bone density value at proximal femur of mature 1/3 place of small animal imaging technology.Small animal imaging is shown in accompanying drawing 3, and the bone density value at Whole Body Bone Scanning density value and near end of thighbone 1/3 place is in Table 6.Rat vena ophthalmica clump is got blood in 4 ℃ and centrifugal 10 min of 1000 g, divides and gets serum, and the content results of measuring serum alkaline phosphatase (AKP) and Tartrate resistant acid phosphatase (StrACP) according to mensuration test kit detail specifications is in Table 6.Result shows, Yam total saponin high dose group can significantly improve the Whole Body Bone Scanning density of diabetes rat and the bone density value at proximal femur of mature 1/3 place.And the AKP in serum and StrACP are had to significant regulating action.
Therefore Yam total saponin causes diabetes complication osteoporosis and decreased renal function have therapeutical effect.
The osteoporotic impact of table 6 Yam total saponin on diabetes-induced
Compare * * P < 0.01, * P < 0.05 with model group.
Claims (3)
1. a Yam total saponin is treated the application in diabetes and complication medicine thereof in preparation.
2. the application of Yam total saponin according to claim 1 in preparation treatment diabetes and complication medicine thereof, is characterized in that the application in preparation treatment acute hyperglycemia, type Ⅱdiabetes mellitus or heritability diabetes medicament.
3. the application of Yam total saponin according to claim 1 in preparation treatment diabetes and complication medicine thereof, is characterized in that medicine for treating osteoporosis or the application in the renal hypofunction medicine of preparation treatment diabetes-induced at preparation treatment diabetes-induced.
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CN101530532A (en) * | 2008-03-11 | 2009-09-16 | 北京凯瑞创新医药科技有限公司 | Oral pharmaceutical preparation of yam total sapogenin and preparation method and application thereof |
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CN101530532A (en) * | 2008-03-11 | 2009-09-16 | 北京凯瑞创新医药科技有限公司 | Oral pharmaceutical preparation of yam total sapogenin and preparation method and application thereof |
Non-Patent Citations (1)
Title |
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王颜刚: "《首届国际中西医结合内分泌代谢病学术大会暨糖尿病论坛论文集 》", 31 October 2008 * |
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Application publication date: 20140219 |