CN103432207B - Preparation method of fructus forsythiae extract lignan and application of extract in blood sugar reducing drugs - Google Patents
Preparation method of fructus forsythiae extract lignan and application of extract in blood sugar reducing drugs Download PDFInfo
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Abstract
The invention relates to a preparation method of a fructus forsythiae extract lignan and an application of the extract in blood sugar reducing drugs. The problem that a substance for preparing the blood sugar reducing drugs can be extracted from fructus forsythiae can be effectively solved. The extract is obtained through the following steps of crushing fructus forsythiae into medical powder, soaking the medical powder in ethanol for 0.5 h, carrying out reflux extraction twice, abandoning filter residue to obtain an extract liquid, performing decompression concentration on the extract liquid until no alcohol smell is left, adjusting the concentration of the medical liquid to be equivalent to contain 0.5 g/ml of a crude drug, thereby obtaining a sample liquid; applying the sample liquid to a type AB-8 macroporous adsorption resin column; eluting by using water in an amount which is 8 times of the volume of the column to obtain and abandon an eluate I; next, eluting by using ethanol in an amount which is 8 times of the volume of the column so as to obtain and abandon an eluate II; and finally, eluting by using ethanol in an amount which is 10 times of the volume of the column so as to obtain an eluate III, recovering the ethanol, and then carrying out decompression concentration and drying to obtain the fructus forsythiae lignan. According to the invention, the raw materials are rich, the preparation method is simple, the prepared fructus forsythiae lignan has the effect of reducing blood sugar and can be effectively used for preparing the blood sugar reducing drugs; therefore, a new application of treating diabetes is developed.
Description
Technical field
The present invention relates to medicine, particularly a kind of preparation method of Fructus Forsythiae extract lignanoid and the application in hypoglycemic medicine thereof.
Background technology
Diabetes to be interacted by environmental factors and inherited genetic factors and what cause take chronic hyperglycemia as the chronic metabolic disease of common trait, domestic to its symptom so-called " hyperglycemia ".Long-term hyperglycemia can cause microvascular endothelial to produce pathological changes, and adjoint protein, lipid metabolism can cause the exception of the organizational structuries such as the heart, brain, kidney, nerve, blood vessel and function extremely, even can cause organ failure and threat to life.Fruity gives its another name " reticent killer ", and the particularly diabetes of adult type, diabetics on average can reduce by 10 year life-span.And the complication occurred can spread all over whole body, and the complication of diabetes comprises: self-disciplining nervous disorder, neurological disorder, cerebral thrombosis, cerebral infarction.Cataract, decayed tooth, stomatitis, bronchitis, dermatosis, myocardial infarction, uremia, pedopathy change etc.Asia diabetes association reveals, by 2012, the total number of persons of middle national trouble diabetes reached 9,240 ten thousand, and has following characteristics: 1 sickness rate is high, can reach 9.7%; 2 rejuvenation trend, between twenty and fifty shortage, moves, and causes diabetes occurred frequently; 3 exist treatment mistaken ideas, and the time of diabetes mellitus in China patient insulin injection is general more late.China is populous nation, population proportion is large, simultaneously Chinese be also diabetes send out crowd well, research display, at rich countries, Chinese's prevalence is many more than 10%, and the sickness rate of nearly 20 years China's diabetes rises rapidly, has caused the attention of the Chinese government, hygiene department and numerous medical workers.
Diabetes are the metabolic diseases caused by different pathogeny, and feature is state of chronic hyperglycemia because defect of insulin secretion or insulin action defect cause and carbohydrate, fat and protein metabolism disorder.Its chronic complicating diseases has nephropathy, neuropathy etc., because oral antidiabetic is convenient, fast, no pain, the advantages such as sustainable prolonged application, clinical practice is very extensive, treatment diabetes conventional at present and the medicine of complication have a few class: 1 biguanides, insulin is recovered to the inhibitory action of adenylate cyclase activity by liver plasma membrane G-protein, the allophone and the hepatic glucose that decrease hepatic glycogen export, promote the anerobic glycolysis of myocyte's glucose, increase the peripheral tissues such as muscle to the picked-up of glucose, strengthen the sensitivity of tissue to insulin, to normal person then without blood sugar reducing function.Represent medicine and have metformin etc., metformin can increase lactic acid gathering in blood, can cause lactic acidosis and with gastrointestinal untoward reaction.2 sulphanylureas, mainly act on pancreatic beta cell uelralante.Represent medicine and have glibenclamide, gliclazide, gliquidone etc.3 glucose glycoside enzyme inhibitors, representing medicine has acarbose, miglitol etc., competitive inhibition glucosidase in gastrointestinal tract, delay disaccharidase in enteric cavity, oligosaccharide and polysaccharide release glucose, slight appetite-suppressing, finally reduces post-prandial glycemia, and does not cause hypoglycemia.4 euglycemic agents, representing medicine has rosiglitazone, pioglitazone etc., is can improve skeletal muscle and adipose cell to the absorption of glucose and the output reducing glycogen, improve the sensitivity to insulin, improve insulin-resistant states, improve carbohydrate metabolism, reduce blood glucose value.5 non-sulphanylureas class Insulin-secreting agents, representing medicine has repaglinide, Nateglinide etc., and specific receptor is combined on beta Cell of islet film, makes pancreatic beta cell depolarization, thus promotes insulin secretion.6 dipeptidyl peptidase-4 inhibitors, representing medicine has sitagliptin, can the activity of DPP-4 always, incretin can be protected not to be degraded, stimulating pancreas β cell regeneration.
But western medicine has side effect more, Liver and kidney toxicity can be brought, along with the prevalence of diabetics constantly rises, the side effect that Western medicine in the past brings and insulin use procedure China are difficult to control, a lot of experts and scholars are made to start to find the new drug for the treatment of diabetes, from Chinese medicine, screen effective ingredient is a new effective way, becomes the study hotspot of domestic and international expert.
The traditional Chinese medical science thinks that diabetes spp is in the category of quenching one's thirst, and in "Nei Jing", has controlled clear and definite discussion to the cause of disease of primary disease, pathogenesis, card.The performance of diabetes clinical symptoms is complicated and changeable, is caused by multiple visceral dysfunction, the closest with the relation of spleen, kidney.Modern study finds, the generation development of blood stasis and diabetes has important impact, and blood stasis through diabetes all the time.Cause the reason of blood stasis roughly as follows in diabetic duration: 1 deficiency of YIN causes the stasis of blood, the deficiency of YIN is one of diabetes the important pathogenesis, YIN fluid being insufficient, and due to homogeny of clear fluid and blood, body fluid deficiency is insufficiency of blood then, causes blood circulation not smooth, and blood vessels run not smooth and produce blood stasis.2 scorchingly cause the stasis of blood, and diabetics consumes due to cloudy body fluid deficiency, and insufficiency of water leading to hyperactivity of fire, have scorching flourishing, decoct cloudy blood, make pachyemia, sering is jammed and produces blood stasis more.3 deficiency of vital energys cause the stasis of blood, and diabetics is scorching interior vehement, and not only impairment of body fluid also can consume gas, causes deficiency of both QI and YIN, and the deficiency of vital energy then promotes unable, and blood is slow and produce blood stasis.4 stagnation of QIs cause the stasis of blood, and feelings will does not freely the most easily cause depression and stagnation of QI, and the stagnation of QI affects blood vessels and runs and produce blood stasis.5 prolonged illness must the stasis of blood, and diabetes are as the chronic lifelong participation disease of one, and its course of disease is delayed, and does not with the passing of time heal, and the traditional Chinese medical science thinks pathogen usually intruding into collateral in protracted disease, and the channels stasis of blood is stagnant, hematogenous blockage and produce blood stasis.Blood stasis, once be formed, can cause the development of diabetes further as new paathogenic factor and increase the weight of again.And pyretic toxicity plays an important role in the generation evolution of diabetic duration, diabetics is all along with scorching clinically, body constitution is biased, is worked with one's mind excessively, depressed emotion, labor stringency, and outer temperature-sensing thermal poison is evil, all can cause burning hot yin-damaging and Qi consuming, and intimately flourishing, or pent up with the passing of time, can pyretic toxicity be turned to.Should with " blood circulation promoting and blood stasis dispelling, heat-clearing and toxic substances removing " blood sugar lowering for Therapeutic Principle.
Fructus Forsythiae is the dry fruit of Oleaceae forsythia Fructus Forsythiae, for Chinese medicine, gone through edition Pharmacopoeia of the People's Republic of China record, bitter in the mouth, row is slightly cold, and enters the heart, lung, small intestine meridian, has effect of heat-clearing and toxic substances removing, mass dissipating and swelling eliminating, dispelling wind and heat pathogens, clinical be used for the treatment of calentura from the beginning of, anemopyretic cold, heating, vexed, laryngopharynx swelling and pain, macule, erysipelas etc., there is antibacterial, antiviral, antiinflammatory, antiendotoxin, protect the liver, diuresis, antipyretic, antiallergic, the effects such as blood sugar lowering, but the treatment report clinically for diabetes is less.Fructus Forsythiae is rich in plurality of active ingredients, as compositions such as flavone, saponin, lignanoids, polysaccharide, Fructus Forsythiae ester glycoside wherein in lignanoid is one of the antioxidation found from forsythia up to now, composition that antibacterial activity is the strongest, and is the principal character composition of Fructus Forsythiae.So how being extracted, realize Fructus Forsythiae extract and preparing the application in hypoglycemic medicine, is the technical problem that people expect to solve.
Summary of the invention
For above-mentioned situation, for overcoming the defect of prior art, the object of the present invention is just to provide a kind of preparation method of Fructus Forsythiae extract lignanoid and the application in hypoglycemic medicine thereof, effectively can solve and extract for the preparation of the material of hypoglycemic medicine from Fructus Forsythiae.
The technical scheme that the present invention solves is, Fructus Forsythiae extract is preparing the application in hypoglycemic medicine, this extract is that Fructus Forsythiae powder is broken into medicated powder, medicated powder soak with ethanol 0.5h, reflux, extract, 2 times, filtering residue discards, and obtains extracting solution, and extracting solution is evaporated to without alcohol taste, adjustment liquor strength containing crude drug 0.5g/ml, obtains sample liquid for being equivalent to; In sample liquid, AB-8 type macroporous adsorptive resins, first uses the water elution of 8 times of column volumes, obtains eluent I and discards; Use the ethanol elution of 8 times amount column volumes again, obtain eluent II and discard; Finally use the ethanol elution of 10 times amount column volumes, obtain eluent III, reclaim ethanol, concentrating under reduced pressure is dry, obtains Fructus Forsythiae lignanoid.
Abundant raw material of the present invention, preparation method is simple, and the Fructus Forsythiae lignanoid of preparation has blood sugar reducing function, is effective to prepare hypoglycemic medicine, and the novelty teabag of developing treatment diabetes is the innovations on hypoglycemic medicine.
Detailed description of the invention
Below in conjunction with concrete condition, the specific embodiment of the present invention is elaborated.
The present invention is in concrete enforcement, provided by following technical scheme: Fructus Forsythiae extract is preparing the application in hypoglycemic medicine, this extract is, Fructus Forsythiae powder was broken into the medicated powder of 60-80 mesh sieve, medicated powder 8 times of weight, volumetric concentration are the soak with ethanol 0.5h of 80%, reflux, extract, 2 times, the 1st 1.5h, the 2nd 1h, filtering residue discards, obtain extracting solution, extracting solution is evaporated to without alcohol taste, and adjustment liquor strength containing crude drug 0.5g/ml, obtains sample liquid for being equivalent to; AB-8 type macroporous adsorptive resins in sample liquid, the ratio of applied sample amount and resin volume is 1:12, and resin column blade diameter length ratio is 1:12, first uses the water elution of 8 times of column volumes, obtains eluent I and discards; Again with 8 times amount column volumes, volumetric concentration is the ethanol elution of 10%, obtain eluent II and discard; Finally with 10 times amount column volumes, volumetric concentration is the ethanol elution of 75%, obtains eluent III, reclaims ethanol, concentrating under reduced pressure is dry, obtains Fructus Forsythiae lignanoid, content >=58%; This Fructus Forsythiae lignanoid is effective to prepare hypoglycemic medicine, realizes Fructus Forsythiae lignanoid and is preparing the application in hypoglycemic medicine.
The inventive method is simple, and abundant raw materials, is easy to prepare Fructus Forsythiae lignanoid, and this Fructus Forsythiae lignanoid has blood sugar reducing function, can be used for preparing hypoglycemic medicine, and achieves satisfied effect through experiment, and regarding assay data is as follows:
1 impact on epinephrine induced mice hyperglycemia model
1.1 pharmaceutical agent
Fructus Forsythiae lignanoid of the present invention;
Metformin hydrochloride tablet, Shanghai Sine Pharmaceutical Co., Ltd. produces, lot number 120523; Adrenalin hydrochloride, Tianjin KingYork Amino Acid Co., Ltd. produces, lot number 20120308: normal saline, Zhengzhou Yonghe Pharmaceutical Co, lot number 12042401; Sodium carboxymethyl cellulose, good fortune chemical reagent factory in morning in Tianjin is produced, lot number 20090826; Glucose estimation kit, is produced by Zhongsheng Beikong Biological Science & Technology Co., Ltd. and provides, lot number 120491; Hepatic glycogen measures test kit, builds up Bioengineering Research Institute and produces, lot number 20120728 by Nanjing.
1.2 experimental apparatus
FA (N)/JA (N) series electronic balance, Shanghai Min Qiao precision instrument company limited; UV-2000 ultraviolet-uisible spectrophotometer, Shanghai Techcomp Instrument Ltd. produces; TGL-16G desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces; DZKW-4 type electronic thermostatic water-bath, Beijing Zhong Xing great achievement Instrument Ltd. produces; KDC-160HR High speed refrigerated centrifuge, Zhong Jia branch company of Keda Innovation Co., Ltd produces; BIORAD-680 microplate reader, 680Microplate Reader, Bio-RadLaboratories; Adjustable pipette, is produced by Shanghai Lei Bo Analytical Instrument Co., Ltd.
1.3 laboratory animal
Kunming mouse, male, body weight 18 ~ 22g, Hebei province's Experimental Animal Center provides, the quality certification number: 1209018; Laboratory quality certification SYXK (Henan) 2010-001.
1.4 test method
Abdominal cavity is adopted to annotate adrenergic method to set up mice hyperglycemia model.Before modeling, metformin group, the large, medium and small dosage component of Fructus Forsythiae lignanoid do not give corresponding medicine gavage, and blank group and model group give same volume 0.1%CMC gavage, every day 1 time, successive administration 7 days.In administration the 7th day (fasting 8h), after administration 1h, except normal group, other 11 groups of lumbar injection adrenalin hydrochlorides (0.2mg/kg), the normal saline of normal group lumbar injection same volume, 0.5h posterior orbit venous blood collection, adopts determination of glucose oxidase blood glucose value, cut off abdominal cavity, get same position hepatic tissue and measure hepatic glycogen content.
1.5 statistical method
The medical statistics bag of data analysis SPSS 17.0 for windows carries out the statistical procedures of data information, measurement data average ± standard deviation
represent, compare employing one factor analysis of variance between each group, the neat person of variance test adopts Ridit inspection with least significant difference (LSD) method, heterogeneity of variance person with Games-Howell method inspection, ranked data.
1.6 result
Table 1 on the impact of the blood glucose value of epinephrine induced mice hyperglycemia model and hepatic glycogen content (
n=12)
* compares P<0.01 with model group
Can find out from upper table: with blank group ratio, model group blood glucose significantly raises, and hepatic glycogen content significantly reduces, modeling success is described.With model group ratio, metformin group, each dosage group of Fructus Forsythiae lignanoid each dosage group all significantly can reduce the blood glucose value (P<0.01) after modeling mice; Significantly can raise hepatic glycogen content (P<0.01).Illustrate that Fructus Forsythiae lignanoid, metformin all can to the glycogenolytic phenomenons of glyconeogenesis aggravation regulating liver-QI caused by antiadrenergic drug.
2 impacts on rat diabetes model caused by streptozotocin
2.1 pharmaceutical agent
Fructus Forsythiae lignanoid;
Metformin hydrochloride tablet, extra large Xinyi Pharmaceutical Factory company limited produces, lot number 120523; Streptozotocin, sigma company produces, lot number Z120315; Normal saline, Zhengzhou Yonghe Pharmaceutical Co, lot number 12042401; Glacial acetic acid (analytical pure), Tianjin Heng Xing chemical reagent Manufacturing Co., Ltd produces, lot number 20110103; Formaldehyde, Yantai City in pairs Chemical Co., Ltd. produces, lot number 20111101; Blood sugar kit, Zhongsheng Beikong Biological Science & Technology Co., Ltd. produces, lot number 120511; NOS test kit, Nanjing is built up Bioengineering Research Institute and is produced, lot number 20121208; SOD test kit, Nanjing is built up Bioengineering Research Institute and is produced, lot number 20121215; Glycated serum protein (GSP) testing cassete, Nanjing is built up Bioengineering Research Institute and is produced, lot number 20121019; Nitrogen oxide testing cassete, Nanjing is built up Bioengineering Research Institute and is produced, lot number 20121212; Triglyceride Reagent box, the safe clinical reagent company limited of Beijing Northization produces, lot number 20121105; T-CHOL test kit, the safe clinical reagent company limited of Beijing Northization produces, lot number 20120808; RatIAA ELISA Kit test kit, R & D company produces, LOT:20121101A; Rat INS ELISA Kit test kit, R & D company produces, LOT:20121101A.
2.2 experimental apparatus
FA (N)/JA (N) series electronic balance, Shanghai Min Qiao precision instrument company limited; UV-2000 ultraviolet-uisible spectrophotometer, Shanghai Techcomp Instrument Ltd. produces; TGL-16G desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces; DZKW-4 type electronic thermostatic water-bath, Beijing Zhong Xing great achievement Instrument Ltd. produces; KDC-160HR High speed refrigerated centrifuge, Zhong Jia branch company of Keda Innovation Co., Ltd produces; BIORAD-680 microplate reader, 680Microplate Reader, Bio-RadLaboratories; Adjustable pipette, is produced by Shanghai Lei Bo Analytical Instrument Co., Ltd.
2.3 laboratory animal
Cleaning grade SD rat, male, 180-220g, Hebei province's Experimental Animal Center provides, the animal quality certification number: 1210019, laboratory quality certification SYXK (Henan) 2010-001.
2.4 test method
The method of sublingual vein annotation streptozotocin is adopted to set up rat diabetes model.Buy animal and normally raise 3 days, according to body weight, the streptozotocin of sublingual vein injection 10mg/ml concentration, dosage is 40mg/kg, tail venous blood sampling after 5 days, side serum blood glucose value, and choose blood glucose value > 16.0mg/L, and obviously there is the rat of polydipsia polyphagia polyuria symptom, according to the random even group-division of blood glucose value, metformin group, the large, medium and small dosage component of Fructus Forsythiae lignanoid do not give relative medicine gavage, blank group and model group give same volume 0.1%CMC gavage, every day 1 time, administration every day 1 time, successive administration 30 days.Respectively at the 10th, 20,30 day of administration, after when perfusion 2, tail vein blood, separation of serum, survey fasting 6 hours blood glucose value, last administration is after 2 hours, and eyeball gets blood, surveys serum insulin (Ins), insulin antibody, NO level and NOS vigor, triglyceride (TG), cholesterol (TC), superoxide dismutase (SOD), glycation serum protein.Put to death rat after getting blood, get pancreas, kidney is cut into slices, by its pathological change of electron microscopic observation.
2.5 statistical method
The medical statistics bag of data analysis SPSS 13.0 for windows carries out the statistical procedures of data information, measurement data average ± standard deviation
represent, compare employing one factor analysis of variance between each group, the neat person of variance test adopts Ridit inspection with least significant difference (LSD) method, heterogeneity of variance person with Games-Howell method inspection, ranked data.
2.6 result
Table 2 on the impact of rat diabetes model SOD, NO, NOS caused by streptozotocin (
n=12)
* compares P<0.05 with model group than P<0.01, * and model group
Can find out from upper table: with blank group ratio, model group SOD vigor significantly reduces (P<0.01), NO content, NOS vigor significantly raise (P<0.01) and illustrate that modeling treated animal oxidation resistance reduces, NO metabolism disorder.With model group ratio, metformin group significantly can raise (P<0.01) SOD enzyme activity, significantly reduces (P<0.01) NO content and NOS enzyme activity.The big or middle dosage group of Fructus Forsythiae lignanoid can raise (P<0.01) SOD enzyme activity significantly, remarkable reduction (P<0.01) NO level and NOS enzyme activity, Fructus Forsythiae lignanoid small dose group significantly can raise (P<0.01) SOD enzyme activity (P<0.01), obviously reduces (P<0.05) NOS enzyme activity.
Table 3 on the impact of rat diabetes model T-CHOL, triglyceride caused by streptozotocin (
n=12)
* compares P<0.05 with model group than P<0.01, * and model group
As can be seen from the above table, compared with blank group, model group T-CHOL, content of triglyceride significantly rise (P<0.01), illustrate that diabetes model can cause disorders of lipid metabolism.Compared with model group, metformin group can reduce the content of (P<0.01) triglyceride and T-CHOL significantly, effective correcting lipid disorder phenomenon.Fructus Forsythiae lignanoid large, medium and small dosage group, Herba Scutellariae Barbatae flavone large, medium and small dosage group, the large, medium and small dosage group of Herba Violae flavone significantly can reduce the content of (P<0.01) T-CHOL, triglyceride, correcting lipid disorder phenomenon.
Table 4 on chain urea assistant bacterium caused by rat diabetes model glycated serum protein, insulin, insulin antibody impact (
n=12)
* compares P<0.05 with model group than P<0.01, * and model group
As can be seen from the above table: model group significantly can raise glycated serum protein content and insulin antibody level (P<0.01) compared with blank group, insulin content (P<0.01) can be reduced significantly, modeling success is described.Metformin group significantly can reduce (P<0.01) glycated serum protein content, insulin antibody level compared with model group, significantly can raise insulin content (P<0.01).The large, medium and small dosage group of Fructus Forsythiae lignanoid significantly can reduce (P<0.01) glycated serum protein content, significantly raises (P<0.01) insulin level; The big or middle dosage group of Fructus Forsythiae lignanoid significantly can reduce (P<0.05) insulin antibody level.
Table 5 on the impact of rat diabetes model dynamic glucose value caused by streptozotocin (
n=12)
* compares P<0.05 with model group than P<0.01, * and model group
Can find out from upper table: except blank group, the equal no significant difference of blood glucose before the administration of each group, illustrate that grouping evenly.With blank group ratio, at the 10th, 20,30 day, the equal significance of model group blood glucose raises (P<0.01), and the success of modeling type is described.With model group ratio, administration the 10th day, each administration group is little to blood sugar influence, administration the 20th day, the 30th day, the large, medium and small dosage group of Fructus Forsythiae lignanoid and metformin group all significantly can reduce blood sugar level (P<0.01).Illustrate that Fructus Forsythiae lignanoid can effectively reduce animal pattern blood glucose value, improve diabetic symptom.
Table 6 is on the impact of rat diabetes model pancreatic tissue caused by streptozotocin
In "-" pancreatic tissue, islets of langerhans is more than 4, and islet cells endochylema enriches, and nucleus is loose; In "+" pancreatic tissue, islets of langerhans is more than 4, the atrophy of minority islet cells endochylema, and a few cell core is intensive; In " ++ " pancreatic tissue, islets of langerhans is at 2-3, the atrophy of part islet cells endochylema, and part nucleus is intensive; In " +++ " pancreatic tissue, islets of langerhans is at 0-1, and whole islet cells endochylema almost disappears, and whole nucleus is intensive
As can be seen from the above table: rats in normal control group pancreas is normally, the cell mass that islets of langerhans is rounded or oval, sharpness of border, and in islets of langerhans, β cell is intensive, distribution rule, form is regular, and structure is normal, and endochylema enriches.Model group animal insulin cell cytosol reduces and atrophy, and form is irregular, and number obviously reduces, the intensive imagination of nucleus, and β cell size differs, and the pancreas of modeling animal damages to check P<0.01 to illustrate through Ridit.Contrast with model group, metformin group can the atrophy of partial agonistic beta Cell of islet, makes part endochylema be restored (P<0.01).Fructus Forsythiae lignanoid heavy dose group cell number is more, endochylema comparatively abundant (P<0.01), and in Fructus Forsythiae lignanoid, small dose group the phenomenon of partial agonistic β cell cytosol atrophy can have significant difference (P<0.01).
Table 7 is on the impact of rat diabetes model kidney caused by streptozotocin
"-": glomerule, renal capsule, renal tubules are substantially all normal; "+": messangial cell is hypertrophy to some extent, capsular space slightly narrows, and renal cells is edema slightly, and tube chamber narrows; " ++ ": the obvious hypertrophy of messangial cell, capsular space part narrows, renal cells edema, and tube chamber narrows; " +++ ": the remarkable hypertrophy of messangial cell, capsular space narrows or disappears, and the obvious edema of renal cells, tube chamber narrows or disappears
As can be seen from upper table and pathological photograph: blank group basement membrane uniformity, without obviously thickening, glomerular capillary chamber without narrow, glomerule interstitial NIP cell invasion.Model group glomerular capillary chamber subsides, inaccessible, and glomerular volume increases, lymphocytic infiltration, and basement membrane thickened and extracellular matrix increase; Renal cells swelling, in renal interstitial, large amount lymphocyte and mononuclear phagocyte infiltrate, and the kidney of modeling animal damages to check P<0.01 to illustrate through Ridit.Contrast with model group, metformin group mesonephric glomerulus, renal cells and interstitial normal (P<0.01).The heavy dose of group of Fructus Forsythiae lignanoid can alleviate extensive edema and the interstitial cell infiltration phenomenon (P<0.01) of renal cells; In Fructus Forsythiae lignanoid, small dose group partly can protect glomerule and renal tubules (P<0.01).
Table 8 is on the impact of rat diabetes phantom heart tissue caused by streptozotocin
"-": myocardial cell is normal, invades profit without congested and inflammatory cell; "+": myocardial cell is disorderly, congested and invade profit without inflammatory cell; " ++ ": the disorderly thickness of myocardial cell differs, and nucleus increases, and congested and inflammatory cell invades profit; " +++ ": the disorderly obviously thickness of myocardial cell differs, and nucleus showed increased, obviously congested and inflammatory cell invades profit
As can be seen from upper table and pathological photograph: naive animals myocardial cell marshalling, interstitial is without congested and cell infiltration, all normal, compared with blank group, model group myocardial cell arrangement disorder, cardiac muscle fiber atrophy, interstitial is congested and cell infiltration obviously, through Ridit inspection, P<0.01, illustrates that pathological changes appears in animal pattern heart.Compare with model group, metformin group myocardial cell marshalling, myocardial cell atrophy is restored, and interstitial is without congested and cell infiltration (P<0.01).The large, medium and small dosage group myocardial cell arrangement of Fructus Forsythiae lignanoid arranges, and part resists myocardial atrophy (P<0.01).
Table 9 is on the impact of rat diabetes model liver organization caused by streptozotocin
"-": hepatocyte, sinus hepaticus normally, invade profit without the congested inflammatory cell that squeezes; "+": hepatocyte, sinus hepaticus normally, have the congested inflammatory cell that squeezes to invade profit; " ++ "; Slight hepatic cell edema, sinus hepaticus narrows, and has the congested inflammatory cell that squeezes to invade profit; " +++ ": hepatocyte edema and acidophile degeneration, sinus hepaticus narrows or disappears, and has congested squeezing to invade profit with inflammatory cell
As can be seen from upper table and pathological photograph: blank group hepatocyte radially arranges, hepatic cords and sinus hepaticus high-visible.Compared with blank group, around the central vein of model group liver of laboratory animal, hepatocyte radially arranges, periphery arrangement disorder, part of hepatocytes is that acidophilia changes, sinus hepaticus narrows, and visible focal hepatic necrosis and cell infiltration, check through Ridit, P<0.01, illustrates that pathological changes appears in animal pattern liver.Compared with model group, the hepatocyte of metformin group liver of laboratory animal radially arranges, hepatic cords and sinus hepaticus high-visible (P<0.01).The hepatocyte of Fructus Forsythiae lignanoid large, medium and small dosage group liver radially arranges, hepatic cords and sinus hepaticus high-visible (P<0.01).
Table 10 is on the impact of rat diabetes model lung tissue caused by streptozotocin
"-": around bronchioles, trachea, alveolar septum and alveolar all normal; "+": around bronchioles, trachea, alveolar septum mild hyperaemia and inflammatory cell invade profit and thicken, without secretions in alveolar; " ++ ": bronchioles epithelial cell Mild edema, around trachea, inflammatory cell invades profit, and the congested inflammatory cell of alveolar septum is invaded and moistened and thicken, without secretions in alveolar; " +++ ": bronchioles epithelial cell Severe edema, around trachea, a large amount of inflammatory cell invades profit, and the congested inflammatory cell of alveolar septum is invaded and moistened and thicken, and is full of a large amount of inflammatory cell in alveolar
As can be seen from upper table and pathological photograph: the bronchioles in blank group lungs, respiratory bronchus, alveolar septum visible inflammatory cell ooze out and congested phenomenon, and lung interval is broadening, be owing to raising the result causing interstitial pneumonia for a long time.Compared with blank group, the extensive cell infiltration of peribronchiolar in model group lungs, the visible a large amount of cell infiltration of alveolar and interval occurs that alveolar disappears, there is edema phenomenon in bronchial mucosa epithelial cell, have no inflammatory exudation in tube chamber, without exudate in alveolar, check through Ridit, P<0.01, illustrates that pathological changes appears in animal pattern lung.Compared with model group, metformin group partly can be improved inflammatory cell in alveolar septum and ooze out and congested phenomenon (P<0.01).Fructus Forsythiae lignanoid large, medium and small dosage group all can be oozed out and congested phenomenon by inflammatory cell in improvement alveolar septum in various degree, improves lung pathology situation (P<0.01).
Shown by above-mentioned data, Fructus Forsythiae lignanoid prepared by the present invention has the effect of blood sugar lowering, is effective to hypoglycemic medicine, expands the medical value of Fructus Forsythiae, is the innovation in medicine preparation, has good economic and social benefit.
Claims (1)
1. the application of hypoglycemic medicine lignanoid in preparation treatment diabetes medicament of a Fructus Forsythiae extraction, this hypoglycemic medicine lignanoid is, Fructus Forsythiae powder was broken into the medicated powder of 60-80 mesh sieve, medicated powder 8 times of weight, volumetric concentration are the soak with ethanol 0.5h of 80%, reflux, extract, 2 times, 1st 1.5h, the 2nd 1h, filtering residue discards, and obtains extracting solution, and extracting solution is evaporated to without alcohol taste, adjustment liquor strength containing crude drug 0.5g/ml, obtains sample liquid for being equivalent to; AB-8 type macroporous adsorptive resins in sample liquid, the ratio of applied sample amount and resin volume is 1:12, and resin column blade diameter length ratio is 1:12, first uses the water elution of 8 times of column volumes, obtains eluent I and discards; Again with 8 times amount column volumes, volumetric concentration is the ethanol elution of 10%, obtain eluent II and discard; Finally with 10 times amount column volumes, volumetric concentration is the ethanol elution of 75%, obtains eluent III, reclaims ethanol, concentrating under reduced pressure is dry, obtains Fructus Forsythiae lignanoid.
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| CN107663188B (en) * | 2017-10-27 | 2020-02-04 | 河南中医药大学 | Cortex lycii total lignan amide alkaloid extract and preparation method and application thereof |
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| CN1899382A (en) * | 2006-07-18 | 2007-01-24 | 上海玉森新药开发有限公司 | Method for preparing forsythia fruit effective part |
| CN101152261A (en) * | 2007-09-04 | 2008-04-02 | 北京理工大学 | Application of phenyl ethyl alcohol glycosides and xylogen glycosides component in forsythia (fruit or leaf) |
| CN101912446A (en) * | 2010-08-19 | 2010-12-15 | 厦门大学 | Application of forsythia chloroform extracts to preparing medicine for treating diabetes mellitus |
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| JP2003063971A (en) * | 2001-08-23 | 2003-03-05 | Tama Seikagaku Kk | Leaf of forsythia, its extract and its use |
| KR20050072275A (en) * | 2004-01-06 | 2005-07-11 | 주식회사 엠디바이오알파 | Diabete treatment with forsythiae fructus |
| KR100658002B1 (en) * | 2005-03-25 | 2006-12-14 | 주식회사 대평 | A method for isolation and purification of matairesinol and arctigenin from Forsythiae FructusForsythia viridissima Lindley |
| CN1864705A (en) * | 2005-05-16 | 2006-11-22 | 上海诺仁生物医药技术有限公司 | An arctium fruit extract, its preparation method and application |
| CN101618075A (en) * | 2008-07-03 | 2010-01-06 | 河南大学 | Blood-sugar-lowering effective parts of traditional Chinese medicine weeping forsythia, extracting method and application thereof |
| JP2010208982A (en) * | 2009-03-10 | 2010-09-24 | Asgen Seiyaku Kk | Ingestion inhibitor |
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| CN101152261A (en) * | 2007-09-04 | 2008-04-02 | 北京理工大学 | Application of phenyl ethyl alcohol glycosides and xylogen glycosides component in forsythia (fruit or leaf) |
| CN101912446A (en) * | 2010-08-19 | 2010-12-15 | 厦门大学 | Application of forsythia chloroform extracts to preparing medicine for treating diabetes mellitus |
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