CN102813645A - Control effect and mechanism of mangiferin on diabetic encephalopathy - Google Patents
Control effect and mechanism of mangiferin on diabetic encephalopathy Download PDFInfo
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Abstract
The invention relates to novel pharmacologic action of mangiferin, i.e., effects of mangiferin on preventing and treating diabetic encephalopathy. Mangiferin can obviously improve cognitive impairment caused by diabetes, remarkably reduce the level of advanced glycation endproducts (AGF) in the brain and expression of the acceptor RAGE thereof, substantially enhance activity and expression of glyoxalase 1 (Glo-1) in the brain, remarkably reduce the level of interleukin 1-beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in the brain, substantially improve the level of reduced glutathione (GSH) in the brain, remarkably reduce the level of malonaldehyde (MDA) in the brain, substantially improve the activity of superoxide dismutase (SOD) and the level of GSH in serum and substantially reduce the level of MDA in the serum. Mangiferin can be used for preventing and treating diabetic complications like diabetic encephalopathy.
Description
Technical field
The present invention relates to the new pharmacological action of chimonin and mechanism of action, especially chimonin preventive and therapeutic effect to the diabetes encephalopathy.
Background technology
Diabetes encephalopathy (diabetic encephalopathy; DE) be meant diabetes (diabetes mellitus; DM) the progressive generation of prolonged illness patient is the moral function disorder disease of principal character with hypophrenia and cerebral nerve physiology and structural change, is diabetes most common complication in the central nervous system.Under diabetic disease states, the structural change of brain mainly is Hippocampus and cortex atrophy, and changing function mainly is a Cognitive function damage, and a large amount of research reports have affirmed that diabetes cause the fact of cognitive dysfunction.In 2006, (diabetes-associated cognitive decline, proposition DACD) further strengthened the understanding of people to this dysfunction to buzzword diabetes cognitive dysfunction, and becomes the focus of diabetes encephalopathy research.Existing about 3.47 hundred million adults in the whole world suffer from diabetes according to estimates, wherein 40% live in the nations of China and India.Epidemiological investigation and show based on the perspective study of Epidemiological study widely: diabetes are that the cognitive function relevant with the age descends and a dull-witted risk factor; With respect to the ND, the speed that cognitive function descends has increased 1.5-2.0 doubly in diabetics; Likewise, for Alzheimer (Alzheimer's disease, sickness rate AD), 2 times of DM patient's right and wrong DM patient.Most results of study show that the diabetes encephalopathy is a kind of process of brain accelerated ageing, thereby the proposition AD of foreign scholar de la Monte SM seminar is the viewpoint of III type DM.Therefore, the diabetes encephalopathy is becoming one of whole world the world of medicine important research project in this century.
(mangiferin MF), claims Fructus Mangifera Indicae (elite) element again to chimonin, and Chinonin (chinonin) is the C-glucosides of a kind of pair of benzene pyrrones (xanthone), also is a kind of polyphenol compound, and molecular formula is C
19H
18O
11, relative molecular weight is 422.Chimonin is present in fruit, leaf, the bark (being the main active of Folium mangiferae) of Anacardiaceae plant mango (Mangifera indica L.); The liliaceous plant Rhizoma Anemarrhenae (Anemarrhena asphodeloides Bge.) rhizome, aerial parts, and in the plant such as flower of irides Rhizoma Belamcandae [Belamcanda chinensis (L.) DC.], leaf.At present mainly from mango, to be extracted as the master.Chimonin is not seen the report of production and selling both at home and abroad as drug use.Modern pharmacology research shows; Chimonin has and improves cognition, neuroprotective, antiinflammatory, antioxidation, blood sugar lowering, antibiotic, antiviral, multiple pharmacologically active such as anticancer, can be used for preventing and treating cough, asthma, excessive phlegm, analgesia, hepatic cholagogic, diabetes and cancer etc.
Summary of the invention
1. goal of the invention
The objective of the invention is to find the pharmacological action that chimonin is new, promptly chimonin is to the preventive and therapeutic effect of diabetes encephalopathy.In fact, the present invention relates to chimonin to the preventive and therapeutic effect of diabetes Cognitive function damage and possible mechanism of action thereof.
2. technical scheme
Chimonin has preventive and therapeutic effect to diabetic complications such as diabetes encephalopathys, and especially chimonin causes diabetes
Study, memory ability infringement tool improve significantly; Chimonin be through the function that strengthens GLO-1,
Suppress AGEs/RAGE axle, antiinflammatory, anti-oxidation stress etc. and realize above-mentioned effect.
Methylglyoxal claims that again (methylglyoxal MG), is mainly derived from glucolytic intermediate product triose phosphate (comprising dihydroxyacetone phosphate and glyceraldehyde 3-phosphate) to methyl-glyoxal.Under the situation of diabetes, chronic renal failure or aging, alpha-carbonyl aldehyde (like MG) obviously raises in the human body, has surpassed normal level.MG has high response, the high 10000-50000 of its glycosylation specific activity glucose doubly, the arginine residues of orientable modifying protein also irreversibly combines with protein, forms glycated protein (glycation protein) and produces cytotoxicity.Saccharifying is a main cause of the spontaneous damage of the inside and outside protein of physiological system cell; Under the diabetes situation, arginine/lysine residue is increased by 2 ~ 5 times by MG saccharifying degree.MG is that (advanced glycation endproducts, precursor AGEs) have close relation with the development of diabetic complication to advanced glycosylation end products; MG can not in time remove and accumulate, and then quickens the formation of AGEs.And hydrogenation imidazolone (hydroimidazolones) MG-H1 that MG and proteinic arginine residues saccharification form is AGEs main in body tissue and the body fluid, further brings into play its cytotoxicity through forming AGEs.In addition, MG is through the directly generation of induced activity oxygen of the protein in the lesion wire plastochondria, increase oxidative stress and nitrogenize stress ability, suppress antioxidase system activity and GLO-1 activity, cause apoptosis; MG also can increase the release of inflammatory mediator, strengthens inflammatory reaction.
MG belongs to alpha-carbonyl aldehyde.GLO-1 (glyoxalase1; Glo-1) be the rate-limiting enzyme of alpha-carbonyl aldehyde metabolic system in the body; Being present in the Cytoplasm of nearly all cell, is the part of aldoketonutase system, forms the aldoketonutase system with aldoketonutase 2 and cofactor reduced glutathion (GSH).This system with the corresponding active 'alpha '-hydroxy acids of no saccharifying of alpha-carbonyl aldehyde catalysis generation of high saccharogenic activity, is the main detoxification system of alpha-carbonyl aldehyde in the body in the presence of GSH.Glo-1 can in time remove alpha-carbonyl aldehyde such as MG, suppresses the formation of AGEs, and the saccharification that therefore resists MG and AGEs.Glo-1 controls the expression of AGEs and receptor (RAGE) thereof through the level of regulating MG.Glo-1 crosses the dicarbapentaborane saccharifying that expression can reduce mitochondrial protein, reduces the generation of active oxygen and dicarbapentaborane glycated proteins group mark thing, and the mark that reduces oxidative stress and nitrogenize stress damage.
Chimonin is influential to the periphery common complication of diabetes, can protect streptozotocin (streptozocin, the heart that STZ) oxidative stress causes in the inductive diabetes rat and the damage of kidney, and prevent the diabetic nephropathy development effect.Most important is that chimonin also can pass through blood brain barrier and blood-eye barrier, and can reach effective Drug therapy concentration.The pathogenesis of diabetes encephalopathy relates to oxidative stress, proteic nonenzymatic glycosylation, neural inflammation etc.Based on above-mentioned background; We observed chimonin to the preventive and therapeutic effect of the inductive diabetes encephalopathy of STZ rat model and with the relation of the oxidative stress of MG mediation, proteic nonenzymatic glycosylation, neural inflammation, MAIN OUTCOME MEASURES comprises: the expression of cognitive function, fasting glucose, AGEs level and receptor RAGE thereof, Glo-1 express and active, interleukin 1 β (IL-1 β) and tumor necrosis factor (TNF-α) level, superoxide dismutase (SOD) activity, malonaldehyde (MDA) and GSH level etc.Through the various pharmacological testings and the result thereof of above-mentioned chimonin, its preventive and therapeutic effect and mechanism of action thereof to the diabetes encephalopathy is described, thereby is further understood essence of the present invention.
Chimonin is to the influence of DM rat cognitive function.(15,30,60mg/kg) the learning and memory ability to the DM rat all has obvious potentiation to basic, normal, high three dosage of experimental result proof chimonin; The improvement effect of high dose (60mg/kg) is more comprehensive, and in the Morris water maze laboratory, the escape latency of rat, platform pass through number of times and belong to the percentage ratio of the time of staying of quadrant at platform all has significant improvement effect.
Chimonin is to the influence of DM rat AGEs level and receptor RAGE expression thereof.Basic, normal, high three dosage of experimental result proof chimonin all can significantly reduce the protein expression of RAGE in the DM rat hippocampus; The middle and high dosage of chimonin can significantly reduce AGEs level in the DM rat hippocampus, shows that chimonin can obviously suppress the activation of AGEs/RAGE path in the DM state hypencephalon.
Chimonin is to DM rat Glo-1 activity and the influence of expressing.Experimental result finds that basic, normal, high three dosage of chimonin all can significantly increase the protein expression of Glo-1 in the DM rat hippocampus, and the middle and high dosage of chimonin can significantly strengthen the activity of Glo-1 in the DM rat hippocampus, shows that chimonin can obviously raise the function of Glo-1.
Chimonin is to the influence of DM rat inflammation.Basic, normal, high three dosage of experimental result proof chimonin all can significantly reduce IL-1 β and TNF-alpha levels in the DM rat hippocampus, show that chimonin has powerful antiinflammatory action.
Chimonin is to the influence of DM rat oxidative stress.Three dosage of experimental result proof chimonin all can significantly reduce lipid peroxidation product MDA level in DM rat hippocampus and the serum; Three dosage of chimonin all can significantly increase endogenous antioxidant GSH level in the DM rat hippocampus, and middle and high dosage can significantly increase GSH level in the serum; Simultaneously, basic, normal, high three dosage of chimonin all can significantly increase SOD activity in the DM rat blood serum.These results show that chimonin has significant anti-oxidation stress effect.
Chimonin is to the influence of DM rat fasting blood-glucose and body weight.We find, three dosage of chimonin are to the not obviously influence of blood sugar level behind the 7-8h on an empty stomach on DM rat daytime, but the dialogue sky on an empty stomach the blood sugar level behind the 2h remarkable reduction effect is arranged.Dosage is in the remarkable body weight that increases the DM rat of administration 5 and 9 week backs in the chimonin.
3. beneficial effect
Above pharmacological tests shows that the present invention has the following advantages:
(1) the present invention has found new pharmacological action and new medical usage to chimonin, has opened up a new application.
(2) to show that chimonin is prevented and treated diabetes encephalopathy pharmacological effect good in the present invention, and effect is strong, and indicating has good prospect in medicine.
(3) in the Morris water maze test; Chimonin can obviously reduce the DM rat escape latency, increase that platform passes through number of times and at the platform place percentage ratio of the time of staying of quadrant, explain that chimonin has the study of the obvious DM of improvement rat, memory ability.
(4) the present invention shows that chimonin has the effect that AGEs level in the obvious reduction DM rat hippocampus and receptor RAGE thereof express, and the obviously infringement that mediates of CKIs saccharification and AGEs/RAGE axle of chimonin be described.
(5) the present invention show chimonin have in the remarkable enhancing DM rat hippocampus Glo-1 active with the effect of expressing, hint out that chimonin can obviously alleviate the damaging action that carbonyl aldehyde such as MG cause body; Simultaneously, chimonin significantly increases the effect of GSH level (the essential cofactor of Glo-1 performance enzymatic activity), explains that Glo-1 possibly be the action target spot of chimonin.
(6) chimonin obviously reduces IL-1 β and TNF-alpha levels in the DM rat hippocampus, shows that chimonin has powerful antiinflammatory action.
(7) chimonin obviously reduces MDA level in DM rat hippocampus and the serum, increases GSH level in Hippocampus and the serum, strengthens the active effect of SOD in the serum, shows that chimonin has very strong antioxidation.
The specific embodiment
Embodiment 1: chimonin is to the influence of DM rat cognitive function
1 materials and methods
1.1 the male SD strain of laboratory animal rat, in age in 8-9 week, 190-220g is provided by Xuzhou Medical College's Experimental Animal Center.
1.2 medicine and reagent chimonin are available from Kunming Fengshanjian Medicine Research Co., Ltd. (purity>97%), STZ is available from sigma company, and the glucose testing cassete builds up bio-engineering research institute available from Nanjing.
1.3 method
1.3.1 the fasting of modelling male SD rat can't help more than the water 12h; STZ (faces with before being dissolved in the 0.1mol/L sodium citrate buffer solution by the injection of 55mg/kg disposable celiac; PH4.4) carry out modeling, modeling is after three days, and the socket of the eye venous plexus is got the about 0.2ml of blood; 25 ℃, the centrifugal 10min of 3000rpm, separation of serum.Detect fasting glucose (FBG) with glucose kit, get the FBG value greater than 250mg/dl (13.9mmol/L) with less than the rat of 600mg/dl (33.3mmol/L) diabetes rat as success.
1.3.2 divide into groups and the administration diabetes rat that modeling is successful be divided into 4 groups at random according to blood glucose value, be respectively anti-diabetic model group (DM), chimonin low (DM+MF-L), in (DM+MF-M), height (DM+MF-H) dose groups, every group of 10 rats.Other establishes one group of normal control group (Control), every group of 10 rats.The basic, normal, high dose groups of chimonin is respectively by 15,30, and 60mg/kg irritates stomach (by the 10ml/kg volume) and gives chimonin (water is processed suspension), once a day, and continuous 9 weeks.Control group and DM organize to the volume normal saline.Monitor body weight weekly one time, adjustment administration volume, fasting glucose of monitoring in every month.
1.3.3 after 8 weeks of index determining administration, each is organized rat and carries out Morris water maze test, observational learning, memory function, and escape latency, the platform of record rat passes through number of times and the percentage ratio of the time of staying of quadrant at the platform place.Afterwards, each is organized the rat femoral vein and gets blood, separation of serum, and cryopreservation, subsequent use; At once put to death, get brain, separate Hippocampus and cortex ,-80 ℃ of preservations.
1.4 statistical procedures is all results represent with mean ± S.E.M., relatively adopts one factor analysis of variance between many groups, relatively adopts t check carrying out statistical analysis between two groups, < 0.05 expression difference has statistical significance to P.
2 results
2.1 chimonin is to the influence of the study of DM rat, memory function
In the test of Morris water maze; Compare with normal rats; In 4 days training the escape latency of DM rat all significantly increase (P 0.05 or P 0.01), platform passes through number of times (P < 0.05) and the percentage ratio of the time of staying of quadrant significantly reduces (P < 0.01) at the platform place.The escape latency of chimonin low dosage remarkable reduction DM rat at the 3rd day that trains (P 0.05); The escape latency of middle dosage remarkable reduction DM rat at the 1st and 2 day (P 0.05), the escape latency of high dose remarkable reduction DM rat at the 1st, 3 and 4 day (P 0.05); The basic, normal, high dosage of chimonin all can significantly be increased in the time of staying of platform place quadrant percentage ratio (P 0.05 or P 0.01), pass through number of times (P < 0.05) and have only high dose significantly to increase platform.The result sees table 1, table 2.
Table 1 chimonin is to the influence of DM rat learning functionality
Annotate: mean ± S.E.M., * P 0.05, * * P 0.01, compare with the Control group; #P 0.05, compare with the DM group.
Table 2 chimonin is to the influence of DM rat memory function
Annotate: mean ± S.E.M., * P 0.05, * * P 0.01, compare with the Control group; #P 0.05, ##P 0.01 with DM group relatively.
2.2 chimonin is to the influence of DM rat blood sugar and body weight
In whole experiment, the FBG of DM rat is in high-level state always, is significantly higher than normal rat (P < 0.01).The DM rat gives three dosage 4 of chimonin and after 9 weeks, FBG still is in high-level state, with not administration DM rat comparison, no difference of science of statistics (seeing table 3).After the beginning administration; The body weight of DM rat significantly is lower than the body weight (P < 0.01) of normal rat; Dosage is in administration 5 with after 9 weeks in the chimonin, significantly increases the body weight (P < 0.05) of DM rat, other two dosage during administration all to the body weight of DM rat do not make significant difference (seeing table 4).
Table 3 chimonin is to the influence of DM rat fasting blood-glucose
Annotate mean ± S.E.M., * * P 0.01, compare with the Control group.
Table 4 chimonin is to the influence of DM rat body weight
Annotate: mean ± S.E.M., n=10, * * P 0.01, compare with the Control group; #P 0.05, compare with the DM group.
Embodiment 2: chimonin is to the influence of AGEs level in the DM rat hippocampus and receptor RAGE expression thereof
1 materials and methods
1.1 laboratory animal is with embodiment 1.
1.2 the anti-RAGE antibody of medicine and reagent rabbit is available from U.S. Santa Cruz company; The anti-GAPDH antibody of rabbit is available from U.S. Bioworld company; I Collagen Type VI enzyme is available from U.S. sigma company; Alkali phosphatase two is anti-, phenylmethyl sulfonylfluoride (PMSF) and BCA protein testing cassete be available from the green skies, Jiangsu biotech firm, Na
3VO
4With NaF available from traditional Chinese medicines group (Shanghai) chemical reagent company limited.
1.3 method
1.3.1AGEs level determination
Fluorescence spectrophotometry detects the AGEs level.With the Hippocampus BIAO and BEN of preserving, back PBS (pH7.4) buffer of weighing, 4 ℃ of ultrasonic homogenate down by 10 times of amounts (w/v) adding 100mM.Homogenate is behind 4 ℃ of centrifugal 15min of following 10000rpm, and supernatant is used for total protein content and other indexs of correlation are measured.Get deposition,, in deposition, add chloroform/methanol (1:1) 1.0ml, shaken overnight with distilled water washing 3 times.Add methanol (4:1) 0.5ml again, 4 ℃ of centrifugal 5min of following 4000rpm.Deposition is with methanol 1.0ml washing 2 times, and distilled water washs 2 times, reuse pH7.5, and the 0.02mol/LHepes buffer (contains 0.1mol/L CaCl
2) wash 2 times.Be deposited in the 1.0ml Hepes buffer and spend the night under 4 ℃.Centrifugal removal buffer contains particle suspending in the Hepes buffer of I Collagen Type VI enzyme (290U) in 1.0ml, adds each 2.0 μ l of toluene and chloroform.With the blank pipe that only contains Hepes buffer and collagenase is standard, and 37 ℃ of vibration 24h are centrifugal with Digestive system, leave and take supernatant.Detect the fluorescence intensity (content of reflection AGEs) in the supernatant with fluorescence spectrophotometry, excitation wavelength is 370nm, and absorbing wavelength is 440nm.The content of AGEs is represented with the U/mg hippocampal protein.
Measure 1.3.2RAGE express
Western blotting method is measured rage protein and is expressed.Get the hippocampal tissue of-80 ℃ of preservations, extract total protein, the electrophoretic separation sample changes film (nitrocellulose filter), washes film, sealing, and an anti-reaction, two anti-reactions, colour developing scans or takes pictures the variation of ImageJ software analysis protein expression level.Adopt GAPDH as confidential reference items.
1.4 statistical procedures is with embodiment 1.
2 results
2.1 chimonin is to the influence of AGEs content in the DM rat hippocampus
AGEs content significantly increases in the DM rat hippocampus, and in the normal rat hippocampus statistical significance (P < 0.01) is arranged relatively.The middle and high dosage of chimonin can significantly reduce AGEs content in the DM rat hippocampus (P < 0.01), and the result sees table 5.
Table 5 chimonin is to the influence of AGEs content in the DM rat hippocampus (mean ± S.E.M.)
Annotate: * * P 0.01, compare with the Control group; ##P 0.01, compare with the DM group.
2.2 the influence that chimonin is expressed rage protein in the DM rat hippocampus
The relative expression of rage protein significantly increases in the DM rat hippocampus, and in the normal rat hippocampus statistical significance (P < 0.01) is arranged relatively.The basic, normal, high dosage of chimonin all can significantly reduce rage protein in the DM rat hippocampus and express (all P < 0.01), and the result sees table 6.
The influence that table 6 chimonin is expressed rage protein in the DM rat hippocampus (mean ± S.E.M.)
Annotate: * * P 0.01, compare with the Control group; ##P 0.01, compare with the DM group.
Embodiment 3: chimonin is to the influence of Glo-1 activity in the DM rat hippocampus with protein expression
1 materials and methods
1.1 laboratory animal is with embodiment 1.
1.2 medicine and reagent goat-anti Glo-1 antibody are available from U.S. R&D System company; The anti-GAPDH antibody of rabbit is available from U.S. Bioworld company; Methylglyoxal is available from U.S. sigma company; Alkali phosphatase two is anti-, phenylmethyl sulfonylfluoride (PMSF) and BCA protein testing cassete be available from the green skies, Jiangsu biotech firm, Na
3VO
4, NaF and MgSO
4Available from Chemical Reagent Co., Ltd., Sinopharm Group (Shanghai), GSH is available from the rich bio tech ltd that accumulates in Shanghai.
1.3 method
1.3.1Glo-1 determination of activity
Determined by ultraviolet spectrophotometry Glo-1 is active.The Hippocampus homogenate that when measuring the AGEs level, prepares, the supernatant of centrifugal gained is as the sample of Glo-1 determination of activity.Glo-1 determination of activity system comprises that the phosphate-buffered salt (pH6.6) of 50mmol/L potassium contains 8mmol/L MG, 2mmol/L GSH and 10mmol/L MgSO
4, behind the mixing, place more than the 2min; Add 10-30 μ g albumen, behind 25 ℃ of reaction 2min, cooling 2min cessation reaction in mixture of ice and water; In the 240nm wavelength, determined by ultraviolet spectrophotometry product S D-lactoylglutathione growing amount how much reflect the active size of Glo-1.The Glo-1 activity is expressed as the percentage ratio of normal group product growing amount.
1.3.2Glo-1 protein expression is measured
Western blotting method is measured the Glo-1 protein expression.Get the hippocampal tissue serosity that packing preserves (once be used for RAGE express measure), the electrophoretic separation sample changes film (nitrocellulose filter), washes film, sealing, and an anti-reaction, two anti-reactions, colour developing scans or takes pictures the variation of ImageJ software analysis protein expression level.Adopt GAPDH as confidential reference items.
1.4 statistical procedures is with embodiment 1.
2 results
2.1 chimonin is to the active influence of Glo-1 in the DM rat hippocampus
Glo-1 is active in the DM rat hippocampus significantly reduces, for statistical significance (P < 0.01) is relatively arranged between 72%, two group of normal rat hippocampus.The middle and high dosage of chimonin can significantly strengthen in the DM rat hippocampus Glo-1 active (P 0.05 and P 0.01), the result sees table 7.
Table 7 chimonin is to (the mean ± S.E.M.) of the active influence of Glo-1 in the DM rat hippocampus
Annotate: * * P 0.01, compare with the Control group; #P 0.05, ##P 0.01, compare with the DM group.
2.2 chimonin is to the influence of Glo-1 protein expression in the DM rat hippocampus
The proteic relative expression of Glo-1 significantly reduces in the DM rat hippocampus, and in the normal rat hippocampus statistical significance (P < 0.05) is arranged relatively.The basic, normal, high dosage of chimonin all can significantly increase Glo-1 protein expression in the DM rat hippocampus (all P < 0.01), and the result sees table 8.
Table 8 chimonin is to the influence of Glo-1 protein expression in the DM rat hippocampus (mean ± S.E.M.)
Annotate: * P 0.05, compare with the Control group; ##P 0.01, compare with the DM group.
Embodiment 4: chimonin is to the influence of IL-1 β in the DM rat hippocampus and TNF-alpha levels
1 materials and methods
1.1 laboratory animal is with embodiment 1.
1.2 the ELISA test kit of medicine and reagent IL-1 β and TNF-α is available from Shanghai Excell Biology Product Co., Ltd., BCA protein testing cassete is available from the green skies, Jiangsu biotech firm.
1.3 method
Enzyme Linked Immunoadsorbent Assay (ELISA) method is measured IL-1 β and TNF-alpha levels.Get the sample of Glo-1 determination of activity, measure IL-1 β and TNF-alpha levels in the Hippocampus.IL-1 β and TNF-alpha levels are measured in strict accordance with the operating procedure of test kit separately and are carried out.
1.4 statistical procedures is with embodiment 1.
2 results
IL-1 β and TNF-alpha levels significantly increase in the DM rat hippocampus, than having increased respectively in the normal rat hippocampus statistical significance (all P < 0.01) are arranged more all between 2.5 times and 61.3%, two group.The basic, normal, high dosage of chimonin all can significantly reduce IL-1 β and TNF-alpha levels in the DM rat hippocampus (all P < 0.01), and the result sees table 9.
Table 9 chimonin is to the influence of IL-1 β in the DM rat hippocampus and TNF-alpha levels (mean ± S.E.M.)
Annotate: * * P 0.01, compare with the Control group; ##P 0.01, compare with the DM group.
Embodiment 5: chimonin is to the influence of MDA in the DM rat hippocampus and GSH level
1 materials and methods
1.1 laboratory animal is with embodiment 1.
1.2 medicine and reagent MDA and GSH test kit build up bio-engineering research institute available from Nanjing, BCA protein testing cassete is available from the green skies, Jiangsu biotech firm.
1.3 method
Spectrophotometry MDA and GSH level.The Hippocampus homogenate supernatant sample of going bail for and depositing is measured MDA and GSH level in the Hippocampus, carries out in strict accordance with the operating procedure of test kit separately.
1.4 statistical procedures is with embodiment 1.
2 results
The MDA level significantly increases in the DM rat hippocampus, than the increase in the normal rat hippocampus statistical significance (P < 0.01) relatively arranged between 83.3%, two group; The GSH level significantly reduces in the DM rat hippocampus, than the reduction in the normal rat hippocampus statistical significance (P < 0.01) relatively arranged between 23.9%, two group.The basic, normal, high dosage of chimonin all can significantly improve MDA and GSH level in the DM rat hippocampus (all P < 0.01), and the result sees table 10.
Table 10 chimonin is to the influence of MDA in the DM rat hippocampus and GSH level (mean ± S.E.M.)
Annotate: * * P 0.01, compare with the Control group; ##P 0.01, compare with the DM group.
Embodiment 6: chimonin is to the influence of SOD activity, MDA and GSH level in the DM rat blood serum
1 materials and methods
1.1 laboratory animal is with embodiment 1.
1.2 medicine and reagent SOD, MDA and GSH test kit build up bio-engineering research institute available from Nanjing.
1.3 method
Spectrophotometry SOD activity, MDA and GSH level.The serum sample of going bail for and depositing measures that SOD is active, MDA and GSH level, carries out in strict accordance with the operating procedure of test kit separately.
1.4 statistical procedures is with embodiment 1.
2 results
SOD is active in the DM rat blood serum significantly reduces with the GSH level, than having reduced respectively in the normal rat serum statistical significance (equal P < 0.01) is arranged more all between 23.2% and 32.4%, two group; The MDA level significantly increases in the DM rat blood serum, than the increase in the normal rat serum statistical significance (P < 0.01) relatively arranged between 37.5%, two group.The basic, normal, high dosage of chimonin all can significantly strengthen SOD in the DM rat blood serum active (P 0.05 or P 0.01); The middle and high dosage of chimonin all can significantly increase GSH level in the DM rat blood serum (P < 0.05); The basic, normal, high dosage of chimonin all can significantly reduce MDA level in the DM rat blood serum (P 0.05 or P 0.01), the result sees table 11.
Table 11 chimonin is active to SOD in the DM rat blood serum, the influence of MDA and GSH level (mean ± S.E.M.)
Annotate: * * P 0.01, compare with the Control group; #P 0.05, ##P 0.01, compare with the DM group.
Claims (2)
1. chimonin is to the preventive and therapeutic effect of diabetes encephalopathy etc.
2. chimonin study that diabetes are caused, memory ability infringement tool improve significantly.
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| 马楠等: "糖尿病脑病发病机制及神经保护措施研究进展", 《中国老年学杂志》, vol. 32, no. 12, 30 June 2012 (2012-06-30), pages 2646 - 2648 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015158836A1 (en) * | 2014-04-16 | 2015-10-22 | Vital Solutions Swiss Ag | Mangifera indica as a sirtuin 1 activating agent |
| US10596212B2 (en) | 2014-04-16 | 2020-03-24 | Vital Solutions Swiss Ag | Mangifera indica as a Sirtuin 1 activating agent |
| AU2015248754B2 (en) * | 2014-04-16 | 2020-09-10 | Sybille Buchwald-Werner | Mangifera Indica as a Sirtuin 1 activating agent |
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