CN1408360A - Use of algin oligosaccharide in anti-senility and anti-dementia - Google Patents
Use of algin oligosaccharide in anti-senility and anti-dementia Download PDFInfo
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention features the application of algin oligosaccharide in medicine for treating anti-senility and anti-dementia. Mouse with algin oligosaccharide taken has raised spatial learning memory level, 2,3 times raised choline acetylase activity of pallium, 15% raised cerebral antioxidant enzyme SOD activity, 49 % lowered monoamine oxidase B activity and 1.17 times lowered NMDA acceptor activity. Results show that algin oligosaccharide can raise cerebral antioxidant enzyme activity, lower monoamine oxidase B activity, promote the synthesis of acetyl choline, reduce the oxidation activity of nerve transmitter, eliminate the damage of free radical to neure and thus has the anti-senility and anti-dementia functions.
Description
The present invention relates to a kind of algin oligosaccharide, particularly relate to the application of a kind of algin oligosaccharide in defying age and dementia.
The applicant has disclosed a kind of manufacture method of algin oligosaccharide in application number is 01107952.5 Chinese patent, comprise mannuronic acid oligosaccharide (MO) and guluronic acid oligosaccharide (GO) with the produced algin oligosaccharide of this method, the all energy large-scale production of these oligosaccharide, price is low.Learn after further study, algin oligosaccharide have anti-ageing and prevention because of effect dull-witted due to the hyoscine, and not yet seeing effective medicine aspect these diseases for the treatment of at present.
The purpose of this invention is to provide the application of a kind of algin oligosaccharide in anti-ageing and anti-dementia, it can remedy the above-mentioned deficiency on the prior art.
A kind of algin oligosaccharide is characterized in that its medicine as defying age and dementia.
Medicine of the present invention can large-scale production, and is cheap, effectively defying age and dementia.
Below by embodiment the present invention is described.
Adopt the hypodermic method of scopolamine to set up the mouse model of dementia.The concentration of scopolamine aqueous solution is 5mg/kg, and MO and GO are mixed with the mixture of H1 and H2 respectively by the weight ratio of 1: 1 and 1: 5, and they are mixed with aqueous solution respectively, and concentration is 120mg/kg, 0.4ml/ only/day gastric infusion.On inspection; take continuously above-mentioned oligosaccharides after 7 days; compare with model group; the space learning memory level of mouse (Morris water maze laboratory) improves; cerebral cortex choline acetylase (ChAT) activity has improved 2.3 times; antioxidase SOD activity has improved 15% in the brain; the activity decreased to 49% of monoamine oxidase MAO-B; 1.17 times of nmda receptor activity decreaseds, these results show that algin oligosaccharide can improve the activity of antioxidase in the brain, reduces the activity of MAO-B; promote acetylcholine synthetic; thereby reduce the oxidation deactivation of neurotransmitter, eliminate the neuronic damage of radical pair, have anti-ageing and anti-dementia effect.
Algin oligosaccharide in the present embodiment comprises mannuronic acid oligosaccharide and ancient fall oligosaccharide and their mixture.Medicine of the present invention is a marine polysaccharide class medicine, also is called for short marine drug.
Below experiment material and method and experimental result are elaborated.Materials and methods 1. animals used as test and grouping
Select healthy Male Kunming strain mice for use, body weight 20 ± 1.6 grams are provided by Chinese Military Medical Science Institute Experimental Animal Center.By random device mouse is divided into six groups, 8 every group.First group is matched group; Second group is independent H1 administration group; The 3rd group is independent H2 administration group; The 4th group is scopolamine administration model group; The 5th group is that model adds H1 administration group; The 6th group is that model adds H2 administration group.2. dosage and method
Two kinds of medicines are provided by pharmaceutical factory of Huahai of Qingdao Marine University.Medicine is an off-white powder, respectively gets 1.12g and is dissolved in the 100ml normal saline.The time spent dilution is 11.2mg/ml, presses 140mg/kg, 0.3ml//the d gastric infusion, and continuous 7 days; Matched group and model group gavage the equivalent distilled water.After beginning to fill with stomach the 8th day, fourth, fifth, six group of disposable hypodermic injection hyoscine 5mg/kg.3.Morris water maze laboratory
Animal 30min and 24h after front 1 day of modeling and modeling carry out the study of Morris water maze totally for 3 times and detect test.Water maze mainly is made up of the platform of a column type pond and a removable position.The high 70cm in pond, diameter 80cm, platform diameter 8cm, the sky, pond is connected with computer by a digital camera.Inject clear water in advance in the pond, depth of water 15cm adds carbon ink and makes Chi Shui become opaque black, and platform surface is a black, and mice can not be seen, the water surface exceeds platform surface 0.5cm.Water temperature is controlled at 22 ± 0.5 ℃, at the place of entry of pond subscript phasing same point as each experiment mice.Platform places in the middle of place of entry quadrant far away, and experimentation keeps gate position constant.Each experiment is exceeded with 120s, and (incubation period, if do not find platform in the setting-up time, computer stopped to follow the tracks of the record animal as the learning and memory achievement, and be 120s writing time from place of entry in-track platform required time.4. enzymatic activity detects
(1) superoxide dismutase (SOD) is measured: after performance testing, the mice broken end is got brain, and homogenate rapidly in ice bath, centrifugal 20 minutes of 4000g gets 3 μ l and carries out the SOD determination of activity.Oxygen radical oxidation azanol forms nitrite in the sample, presents purple under the developer effect.When the SOD vigor was higher, ultra-oxygen anion free radical was reduced the nitrite of formation by narrow spectrum inhibition, surveys its absorbance with visible spectrophotometer, at 550nm place colorimetric estimation SOD vigor.
(2) choline acetylation transferring enzyme (ChAT) determination of activity
Adopt the tagging synthetic method.Get brain homogenate supernatant 20 μ l add 50 μ l reactant liquors (contain chlorination choline 10mmol/L, calabarine sulfate 1mmol/L, ethylenediaminetetraacetic acid 10mmol/L is dissolved in 300mmol/L PBS, pH7.4) and 10 μ l
3The H-S-acetyl-coenzyme-A (
3H-CoA, final concentration 0.1mmol/L), behind 37 ℃ of reaction 30min, with the cold PBS of 3ml (containing chlorination acetylcholine 35.7mg/L) cessation reaction.And add the acetonitrile 2ml contain the 10mg tetraphenylboron sodium, and adding again 6ml toluene scintillation solution, jolting 1min gently makes generation
3H-Ach shifts to the organic solvent layer, measures the CPM value at liquid scintillation numeration instrument behind the 10min.The result generates with every milligram of albumen of per minute
3The mole number of H-Ach is represented.
(3) monoamine oxidase-B (MAO-B) determination of activity
Get and reset and add 40ul PBS on the 10ul brain homogenate, 10ul is hatched 20min after containing isotopic substrate mixing in 37 ℃ of water-baths, HCl cessation reaction with 0.1ml 2mol/L, move into scintillation vial with the centrifugal absorption supernatant of toluene 6ml extractive reaction thing 4ml, every glass adds 5ml toluene scintillation solution, measures the cpm value on liquid scintillation numeration instrument.5. receptors bind experiment
(1) the thick film preparation of brain synapse: the rat broken end adds Tris-acetate buffer solution (50mmol/L with 1: 20 times of volume after getting brain, pH7.4), in ice bath, grind 1min with glass homogenizer, homogenate is in 4 ℃ of centrifugal 30min of 15000g, repeat 4 times, abandon supernatant, with precipitation freeze in-70 ℃ standby, this is the thick film of brain synapse.
(2) m receptor is measured: get the aglucon that the thick film of 100 μ l synapses adds m receptor
3H-QNB (quinuclidinyl benzilate) 10 μ l (final concentration 0.1nmol/L), add the 0.1mmol/L atropine in the non-specific bond pipe, after 60min is hatched in 25 ℃ of water-bath vibrations, add the 0.05M PBS 5ml of pre-cooling, sucking filtration on the plain film of glass fibre, reuse 15ml PBS drip washing.The plain film of glass fibre moves into liquid and dodges in the cup, adds the toluene scintillation solution 7ml that contains triton, and activity is penetrated in measuring on liquid scintillation counter.
(3) nmda receptor is measured: get the thick film of 100 μ l synapses, add the aglucon of nmda receptor
3H-MK801 10 μ l (final concentration 0.5nmol/L).Add cold MK801 in the non-specific bond pipe, after 30min is hatched in 30 ℃ of water-baths vibrations, add the Tris-acetate buffer solution 5ml of pre-cooling, sucking filtration on cellulose membrane, the drip washing of reuse 20ml buffer.Filter membrane moves into liquid and dodges in the cup, adds the toluene scintillation solution 7ml that contains Triton, and activity is penetrated in measuring on liquid scintillation counter.6. protein determination
Adopt the Bradford method.With the protein concentration in the absorbance value working sample behind Coomassie brilliant blue G-250 and the protein interaction, use bovine serum albumin(BSA) as standard protein.7. statistical procedures
Data inputs computer carries out statistical procedures with the Excel 2000 of Microsoft company, and all (Means ± SE) expression relatively uses Student ' st to check to experimental result between group with " mean value standard error ".Experimental result 1. water maze test results:
Detect mice space learning memory ability with Morris water maze method.From the first time learning test can see between each group and search out the no significant difference in incubation period of platform.But behind the modeling 30min, do not inject in three groups of mices of scopolamine, take its incubation period of mice of H1, H2) shorten to 73% and 72% of matched group, illustrate that taking ocean medicine H1, H2 separately to normal mouse has the effect that strengthens learning and memory, also see effect same behind the 24h.But medicine is apparent in view to acting on behind the 24h of model mouse, and the incubation period of model mouse this moment is the longest, H1, H2 administration group be respectively its 81% and 76%, improvement effect (table 1) is arranged.
Table 1. marine polysaccharide class medicine H1, H2 seek platform incubation period (second) to the group dosage n that influences of mice Morris water maze laboratory
(mg/kg) 3 control group equivalent physiological saline 8 87.1 ± 15.4 78.5 ± 15.8 46.3 ± 12.3 marine polysaccharide H1 140 8 81.9 ± 15.5 57.3 ± 15.2 35.0 ± 10.3 marine polysaccharide H2 140 8 103.9 ± 13.2 56.4 ± 13.6 37.9 ± 10.9 hyoscines (Sco), 58 87.9 ± 14.0 84.3 ± 14.0 55.5 ± 15.0Sco+H1 5+,140 8 102.5 ± 10.7 75.8 ± 13.1 45.0 ± 11.9Sco+H2 5+,140 8 57.4 ± 16.1 92.0 ± 12.8 42.4 ± 11.52. superoxide dismutase (SOD) activity of the 1st order 2 order
Matched group and model group are not seen notable difference, may be relevant with types of models.But all give the SOD in Mice activity of marine drug all apparently higher than not administration group.H1, H2 are individually dosed, and there were significant differences with the matched group ratio, p＜0.001; H2 has obvious potentiation to model group SOD, p＜0.05, and the effect of H1 is more remarkable, p＜0.001.See Table 2.
Table 2. marine polysaccharide class medicine H1, H2 compares with matched group active group dosage (mg/kg) n SOD activity (UN/mg prot.) matched group equivalent normal saline 8 61.20 ± 1.05 marine polysaccharide H1 140 8 68.86 ± 1.58 * marine polysaccharide H2 140 8 68.65 ± 0.86 * scopolamine (Sco) 58 62.93 ± 2.71Sco+H1 5+,140 8 69.71 ± 1.71 #Sco+H2 5+,140 8 72.30 ± 1.95 ##*p＜0.001 that influences of mouse brain SOD; #p＜0.05; 3. choline acetyltransterases (ChAT) activity is compared with model group in ##p＜0.001
Model group ChAT activity is lower than control group, but does not have obvious statistical significance.In the administration group, only have its ChAT activity of model H2 administration group to improve 2.23 times, utmost point significant difference is arranged.Other administration group changes not obvious, sees Table 3.
Table 3. marine polysaccharide class medicine H1, H2 affect group dosage (mg/kg) n ChAT activity (pmol/mg prot./min) control group equivalent physiological saline 8 22.72 ± 2.29 marine polysaccharide H1 140 8 18.55 ± 0.75 marine polysaccharide H2,140 8 16.88 ± 2.04 hyoscines (Sco) 58 18.96 ± 1.79Sco+H1 5+,140 8 18.05 ± 1.00Sco+H2 5+,140 8 42.31 ± 5.67##p＜0.001 to mouse brain ChAT activity, with model group 4. MAO-Bs (MAOB) activity relatively
MAO-B is the oxidase of monoamines medium in the metabolism brain, and its activity increases with age growth, is one of important indicator of brain aging.This experiment is observed the interior MAO-B of model group mouse brain and is higher than other any group, but obviously descends through two groups of mouse MAO-B of H1 and H2 administration are active, obvious significant difference is all arranged, the inhibition of H1 stronger (seeing Table 4).
Table 4. marine polysaccharide class medicine H1, H2 affect active (pmol/mg prot./min) the control group equivalent physiological saline of group dosage (mg/kg) n MAO-B 8 358.7 ± 33.6 marine polysaccharide H1 140 8 331.2 ± 25.7 marine polysaccharide H2,140 8 358.8 ± 33.4 hyoscines (Sco) 58 402.4 ± 26.6Sco+H1 5+,140 8 306.8 ± 20.5#Sco+H2 5+,140 8 281.2 ± 19.9###p＜0.05 to mouse brain MAO-B activity; ##p＜0.001 is compared, 5. cholinergic muscarine m receptors with model group and is combined activity
Model group is behind scopolamine 5mg subcutaneous injection, and m receptor has increased in conjunction with active compensatory, and no significant difference between matched group and H1, the H2 administration group illustrates that two medicines can keep this receptor in a normal range.See Table 5.
Table 5. marine polysaccharide class medicine H1, H2 affect group dosage (mg/kg) n to mouse brain Cholinergic m receptor in conjunction with activity
3H-QNB binding, (pmol/mg prot.) control group equivalent physiological saline 8 7.59 ± 0.34 marine polysaccharide H1 140 8 7.07 ± 0.42 marine polysaccharide H2 140 8 7.91 ± 0.23 hyoscine, (Sco) 58 8.04 ± 0.20Sco+H1 5+140,8 7.75 ± 0.17Sco+H2 5+140,8 7.83 ± 0.226. glutamate nmda receptor-binding activity
Glutamic acid is the highest excitatory neuron transmitting medium of brain intensive amount.The important hypotype nmda receptor of its receptor and synaptic plasticity and learning and memory function are closely related.This receptor of this experimental model Mus is minimum in conjunction with activity, but as seen significantly improves after taking H1, H2, and has obvious statistical significance (p＜0.05), sees Table 5.
Table 6. marine polysaccharide class medicine H1, H2 affect group dosage (mg/kg) n to mouse brain Cholinergic nmda receptor in conjunction with activity
3H-MK801 binding (fmol/mg prot.) control group equivalent physiological saline 8 289.45 ± 19.25 marine polysaccharide H1 140 8 287.70 ± 20.30 marine polysaccharide H2,140 8 307.65 ± 10.50 hyoscines (Sco) 58 252.35 ± 16.45Sco+H1 5+,140 8 292.60 ± 21.35Sco+H2 5+,140 8 294.35 ± 11.55##p＜0.05 is with the model group ratio
Claims (1)
1, a kind of algin oligosaccharide is characterized in that its medicine as defying age and dementia.
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| CN103340881A (en) * | 2013-07-09 | 2013-10-09 | 中国科学院上海药物研究所 | Application of oligose type compound in neuroprotection |
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