CN104800200A - Medical uses of galangin - Google Patents
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Abstract
The present invention relates to the field of medicine, particularly to medical uses and a drug composition of galangin. The galangin of the present invention can be used for preparation of retinal neovascular disease prevention and treatment drugs.
Description
Technical field
The present invention relates to Medicines and Health Product field, particularly relate to a kind of medical usage and pharmaceutical composition thereof of galangin.
Background technology
Retina neovascular diseases refers to because the growth of intraretinal neovascularization, and with hemorrhage, ooze out, pathologic change such as hypertrophy thus the ocular disease of blinding.At present, retina neovascular diseases has day by day become one of blinding oculopathy the most serious in world wide, comprise diabetic retinopathy (Diabetic retinopathy, DR), retinopathy of prematurity (Retinopathy of prematurity, ROP), age-related macular degeneration (age-related macular degeneration, AMD), retinal vascular occlusive disease, periphlebitis of retina etc.Research confirms, the activity such as differentiation, propagation, migration, blood capillary formation of vascular endothelial cell is the key link of the whole pathological process of retina neovascular diseases, so suppress vascular endothelial cell proliferation and neovascularization growth to be the keys for the treatment of this kind of disease.
Diabetic retinopathy (Diabetic retinopathy, DR) is one of most important performance in diabetic microangiopathy, and being a kind of retinopathy having specificity and change, is one of severe complication of diabetes.Clinically according to whether occurring that retinal neovascularization is mark, nonproliferative diabetic retinopathy (nonproliferative diabetic retinopathy is called by there is no the diabetic retinopathy of retinal neovascularazation, NPDR) (or claiming simple type or background type), and by there being the diabetic retinopathy of retinal neovascularazation to be called, proliferating diabetic retinopathy becomes (proliferative diabetic retinopathy, PDR).
Retinopathy of prematurity (Retinopathy of prematurity, ROP) is the class disease caused by neonatal retinal vessel abnormality proliferation, and with premature labor, low birth weight, to accept the factors such as oxygen therapy relevant.Be common in birth latter 3 ~ 6 weeks, be divided into active stage and fibrous membrane Formation period clinically.The treatment of retinopathy of prematurity mainly relies on the medical treatment such as surgical operation and neovascularization inhibitor.
Age-related macular degeneration (age-related macular degeneration, AMD) also known as senile degeneration of macula, for the Aging of macular area structure changes.To be retinal pigment epithelium engulf digestion power to acromere dish film to main manifestations declines, result make not by the dish film residual body retention of catapepsis in basilar part cell oleo stock, and to discharge to extracellular, be deposited on Bruch film, form glass-film wart.Glass-film wart causes this fracture of Bruch film then, under choriocapillary enters RPE by the Bruch film broken and under neuroepithelium of retina, forms choroidal neovascularization.Due to the textural anomaly of new vessels wall, cause the seepage of blood vessel and hemorrhage, and then cause a series of Secondary cases pathological change.Age-related macular degeneration betides more than 45 years old mostly, and its prevalence increases with the age and increases, and is the important diseases of current old people's blinding.Primary disease is divided into dryness and moist amphitypy clinically.The feature of wet age related macular degeneration has active new vessels under pigment epithelium layer, thus cause a series ofly to ooze out, hemorrhage, cicatrix changes.
Galangin (Galangin) is the main component contained in zingiberaceous plant Rhizoma Alpiniae Officinarum Alpinia officinarum Hance root.Rhizoma Alpiniae Officinarum is one of Chinese medicine with important medical value, and it has pharmacological action widely, as antiulcer, diarrhea, antalgic and inflammation relieving, antithrombus formation, antioxidation, antibacterial and anti-promoting etc.
Summary of the invention
Object of the present invention aims to provide a kind of new medical usage and pharmaceutical composition thereof of galangin.
Specifically, a first aspect of the present invention there is provided the application of galangin in preparation RF-6A inhibition of cell proliferation.
In a preference, described RF-6A cell proliferation is induced by VEGF and is produced.
A second aspect of the present invention there is provided the application of galangin in the medicine of preparation control retina neovascular diseases.
A third aspect of the present invention there is provided the application of galangin in the medicine of preparation control diabetic retinopathy.
In a preference, described diabetic retinopathy is that proliferating diabetic retinopathy becomes.
A fourth aspect of the present invention there is provided the application of galangin in the medicine of preparation control retinopathy of prematurity.
A fifth aspect of the present invention there is provided galangin and is preparing the application prevented and treated in the medicine of age-related macular degeneration.
In a preference, described age-related macular degeneration is wet age related macular degeneration.
A sixth aspect of the present invention there is provided a kind of pharmaceutical composition suppressing retinal neovascularization, and it comprises the galangin for the treatment of effective dose.
The details of various aspects of the present invention is able to detailed description by chapters and sections subsequently.By hereafter and the description of claim, feature of the present invention, object and advantage will be more obvious.
Accompanying drawing explanation
Fig. 1 a is retina partial enlarged drawing (100 ×), embodies CD31 immunofluorescence dyeing and detects galangin of the present invention induces new vessels in DR mice and normal mouse retina effect to STZ;
A. Normal group, b. diabetic retinopathy model group, c. galangin 1mg/kg, d. galangin 10mg/kg;
Fig. 1 b is that (Data=Mean ± SD, n=6-8 compare * * * P<0.001, compare with DR Model group vascular counts cartogram with Control group
##p<0.01,
###p<0.001);
Fig. 2 embodies galangin of the present invention, and on the impact of VEGF content in diabetic mice serum and vitreous chamber, (Data=Mean ± SD, n=6-8 compare with Control
* *p<0.001, compares with DR model group
###p<0.001);
Fig. 3 a is retina partial enlarged drawing (100 ×), embodies CD31 immunofluorescence dyeing and detects galangin (Galangin) to the effect of new vessels in OIR Mouse Retina;
A. Normal group, b.OIR model group, c.Galangin20mg/kg;
Fig. 3 b is that (Data=Mean ± SEM, n=6-8 compare * * * P<0.001, compare with OIR Model group vascular counts cartogram with Control group
###p<0.001).
Detailed description of the invention
Appearance part of the present invention is based on so unexpected discovery: the propagation of the retinal endothelial cell RF-6A that galangin (Galangin) can significantly suppress VEGF to induce.Therefore, above-claimed cpd can be expected to develop becomes a kind of material and the RF-6A inhibition of cell proliferation that suppress RF-6A cell proliferation.As known to persons skilled in the art, described " RF-6A inhibition of cell proliferation " can be various forms of material, includes but not limited to: medicine, health product, article of everyday use etc.And then, can be used for preventing and treating various retina neovascular diseases with " RF-6A inhibition of cell proliferation " prepared by galangin, these diseases include but not limited to: diabetic retinopathy (Diabetic retinopathy, DR), retinopathy of prematurity (Retinopathy of prematurity, ROP), age-related macular degeneration (age-related maculardegeneration, AMD), retinal vascular occlusive disease, periphlebitis of retina etc.
And then a first aspect of the present invention there is provided the application of galangin in preparation RF-6A inhibition of cell proliferation.
Preferably, described RF-6A cell proliferation is induced by VEGF and is produced.
A second aspect of the present invention there is provided the application of galangin in the medicine of preparation control retina neovascular diseases.
A third aspect of the present invention there is provided the application of galangin in the medicine of preparation control diabetic retinopathy.
Preferably, described diabetic retinopathy is that proliferating diabetic retinopathy becomes.
A fourth aspect of the present invention there is provided the application of galangin in the medicine of preparation control retinopathy of prematurity.
A fifth aspect of the present invention there is provided galangin and is preparing the application prevented and treated in the medicine of age-related macular degeneration.
Preferably, described age-related macular degeneration is wet age related macular degeneration.
A sixth aspect of the present invention there is provided a kind of pharmaceutical composition suppressing retinal neovascularization, and it comprises the galangin for the treatment of effective dose.
As known to persons skilled in the art, galangin (Galangin) has following general structure:
Molecular formula: C
15h
10o
5molecular weight: 270.2369
Galangin of the present invention obtains from purchases such as Shanghai Institute Center of Standardization for Traditional Chinese Medicine by commercial sources, also extracts from zingiberaceous plant Rhizoma Alpiniae Officinarum Alpinia officinarum Hance root by the conventional method of this area and obtains.Its purity all meets medicinal standard.
So that galangin of the present invention is made medicine.Galangin of the present invention can be used alone or uses with the form of pharmaceutical composition.Pharmaceutical composition comprises galangin of the present invention as active component and pharmaceutically suitable carrier.Preferably, pharmaceutical composition of the present invention contains the galangin of the present invention as active component of 0.1 ~ 99.9% percentage by weight." pharmaceutically suitable carrier " can not destroy the pharmaceutical active of galangin of the present invention, simultaneously its effective dose, and consumption when can play pharmaceutical carrier effect is to human non-toxic.
Described pharmaceutically suitable carrier includes but not limited to: soft phospholipid, aluminium stearate, aluminium oxide, ion exchange material, self-emulsifying drug delivery system, tween or other surfactants, serum albumin, buffer substance are if phosphate, glycine, sorbic acid, water, salt, electrolyte are as sulfate protamine, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, magnesium silicate, satisfied fatty acid partial glyceride mixtures etc.
Other conventional excipient substances are as binding agent (as microcrystalline Cellulose), filler (as starch, glucose, Lactis Anhydrous and lactose beadlet), disintegrating agent (as cross-linked pvp, crosslinked carboxymethyl fecula sodium, cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose), lubricant (as magnesium stearate) and absorption enhancer, absorption carrier, flavouring agent, sweeting agent, excipient, diluent, wetting agent etc.
Galangin of the present invention and its pharmaceutical composition can by the preparations of this area conventional method and can by intestinal or non-bowel or topical routes.Oral formulations comprises capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, unguentum etc.; Non-intestinal drug delivery agent comprises injection etc.; Local administration preparation comprises cream, patch, ointment, spray etc.Be preferably oral formulations.
The route of administration of galangin of the present invention and its pharmaceutical composition can be oral, Sublingual, percutaneous, through muscle or subcutaneous, mucocutaneous, vein, urethra, vagina etc.
Below in conjunction with specific embodiment, set forth the present invention further.Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, the usually conveniently conditioned disjunction condition of advising according to manufacturer.Unless otherwise indicated, otherwise all percent, ratio, ratio or number by weight.
Unless otherwise defined, all specialties used in literary composition and scientific words and one skilled in the art the same meaning be familiar with.In addition, any method similar or impartial to described content and material all can be applicable in the inventive method.The use that better implementation method described in literary composition and material only present a demonstration.
The above-mentioned feature that the present invention mentions, or the feature that embodiment is mentioned can combination in any.All features that patent specification discloses can with any composition forms and use, each feature disclosed in description, anyly can provide identical, alternative characteristics that is impartial or similar object replaces.Therefore apart from special instruction, the feature disclosed is only general example that is impartial or similar features.
The activity of embodiment 1 galangin vitro inhibition retinal neovascularization
The propagation of vascular endothelial cell, migration, segment dislocation are the main experimental methods of in-vitro evaluation angiogenesis.We are on Rhesus Macacus retinal endothelial cell RF/6A cell, observe galangin promotes vascular endothelial cell proliferation, migration and segment dislocation impact to important short Angiogenesis VEGF (Vascular endothelial growth factor, VEGF).In the RF/6A cell proliferation experiment of VEGF induction, the RF/6A cell proliferation that galangin (10 μMs, 25 μMs) can significantly suppress VEGF to induce, and the RF/6A cell of quiescent stage is not significantly affected.The RF/6A cell migration that galangin (2.5 μMs, 5 μMs, 10 μMs, 25 μMs) can obviously suppress VEGF to induce.The segment dislocation of the RF/6A cell that galangin (2.5 μMs, 5 μMs, 10 μMs, 25 μMs) can obviously suppress VEGF to induce.As can be seen here, galangin can suppress the retinal neovascularization of being induced by VEGF in vitro, and VEGF is the topmost angiogenesis promoting factor participating in regulation and control retinal neovascularization.
1.1 experiment material
1.1.1 cell
RF-6A cell strain: be purchased from Shanghai Inst. of Life Science, CAS cellular resources center.
1.1.2 medicine
Galangin purchased from Shanghai Institute Center of Standardization for Traditional Chinese Medicine, purity more than 98%.
1.1.3 reagent
Gelatin and bromination-3(4,5-dimethylthiazole-2) 2,5-xylyl tetrazole (MTT) purchased from American Sigma companies, hyclone (FBS), Matrigel, RPMI1640 culture fluid, 0.25% trypsin purchased from American Invitrogen company.VEGF (VEGF) purchased from American PeproTech company.In experiment, other reagent used is domestic analytical pure.
1.2 experimental techniques:
1.2.1 Pharmaceutical formulations
Galangin DMSO (DMSO) dissolves, and being made into mother liquid concentration is 0.1mol/L, and mother solution all uses primary sterilization filter (0.22 μM) filtration sterilization.By 5 concentration needed for the preparation of serum-free RPMI1640 culture medium during dosing, DMSO total concentration in cultivation is made to be no more than 0.1%.
1.2.2 galangin suppresses RF/6A cell proliferation experiment
To take the logarithm the cell of trophophase, cell is made cell suspension, spread in 96 orifice plates by certain concentration, add after medicine to be measured and cell incubate 48 hours altogether when cell attachment growth conditions is good, add 10 μ l MTT(final concentration 0.5mg/ml) put incubator and react 4 hours, add 50 μ l tri-agent (10%SDS-5% isobutanol-0.01M HCL) fully to dissolve more than 12 hours in incubator, finally measure light absorption value at OD570/630nm place.Cell survival rate (%)=administration group OD(570nm-630nm)/matched group OD(570nm-630nm) × 100%, matched group adds and does not add any medicine containing the cell culture fluid of equivalent DMSO.
1.2.3 galangin suppresses the RF/6A cell proliferation experiment of VEGF induction
To take the logarithm the cell of trophophase, cell is made cell suspension, spread in 96 orifice plates by certain concentration, when cell attachment growth conditions is good, abandon former culture medium, change the RPMI1640 culture medium containing 1% hyclone, add medicine to be measured after 15 minutes, add after somatomedin (VEGF) and cell incubate 48 hours altogether, add 10 μ l MTT(final concentration 0.5mg/ml) put incubator and react 4 hours, add 50 μ l tri-agent (10%SDS-5% isobutanol-0.01M HCL) fully to dissolve more than 12 hours in incubator, finally measure light absorption value at OD570/630nm place.Cell survival rate (%)=administration group OD(570nm-630nm)/matched group OD(570nm-630nm) × 100%, matched group adds and does not add any medicine containing the cell culture fluid of equivalent DMSO.
1.2.4 experiment is moved
Transwell cell is with 0.1% gelatin bag by after 1h, and taking-up is dried, and the RF/6A cell serum-free medium digested is washed 3 times, and dilution is 4 × 10
5/ ml, adds 100ul(4 × 10 in upper room
4cells/well) cell suspension.Lower room adds the serum-free medium of 600 μ l, and adds VEGF(10ng/ml), wear film 8 hours.Suck upper and lower room training liquid, fix 30min with 4 DEG C of 4% paraformaldehyde room temperature, wipe the non-migrating cell in upper strata, interior room with cotton swab, 0.1% crystal violet room temperature dyeing 10min.With the unnecessary dye of PBS rinsing.Taking pictures under microscope and count, finally using 10% acetic acid 100ul/ hole extracting 10min, with measuring OD value under microplate reader 600nm.
1.2.5 segment dislocation experiment
Cold fluid matrix glue 30 μ l is spread in the 96 every holes of orifice plate, solidifies 45 minutes at 37 DEG C.Every hole adds 100 μ l cell suspension (1 × 10
4cells/well) add medicine or the contrast of variable concentrations simultaneously, hatch 4 hours.By inversion difference as microscope record image, calculate complete segment dislocation number.
1.2.6 statistical procedures
Experimental data all represents with meansigma methods ± standard error, and adopt SPSS11.5 statistical software to analyze, carry out variance analysis in One-WayANOVA mode, compare between two and adopt LSD method, P<0.05 is for having statistical significant difference standard.
1.3 experimental result
1.3.1 galangin is on the impact of RF/6A cell quiescent stage and VEGF (VEGF) proliferative induction.
From table 1, galangin, in 0 ~ 25 μM, on the propagation of quiescent stage RF/6A cell without impact, illustrates RF/6A cell without obvious cytotoxicity.And galangin starts all to suppress VEGF to induce the propagation of RF/6A cell in 2.5 μMs of concentration significance, and in dose dependent.
Table 1 galangin is to the suppression ratio (n=10) of RF/6A cell quiescent stage and VEGF proliferative induction
Compare with solvent group, * * P<0.01; * * P<0.001;
1.3.2. galangin induces the impact of RF/6A cell migration on VEGF
From table 2, galangin starts all to suppress VEGF to induce the migration of RF/6A cell in 1 μM explicitly, and in dose dependent.
Table 2 galangin induces the impact (n=6) of RF/6A cell migration to VEGF
Compare with solvent group, * * P<0.01; * * P<0.001;
1.3.3. galangin induces the impact of RF/6A cell segment dislocation on VEGF.
From table 3, galangin starts all to suppress VEGF to induce the segment dislocation of RF/6A cell in 1 μM explicitly, and in dose dependent.
Table 3 galangin induces the impact (n=6) of RF/6A cell segment dislocation to VEGF
Compare with solvent group, * * P<0.01; * * P<0.001
Embodiment 2 galangin improves diabetic retinopathy drug activity
2.1 experiment materials and method
2.1.1 animal: SPF level C57 mice, male, body weight 18-24g, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center.The animal quality certification is numbered: SCXK(Shanghai) 2012-0002.Raise in Shanghai Univ. of Traditional Chinese Medicine SPF level Animal House, raise after one week and use.Rearing conditions is: temperature 22 ± 1 DEG C, humidity 55 ± 5%, and 12 hours Dark-light cycle, freely absorb after feedstuff and water sterilization.Test and carry out in strict accordance with country and Shanghai Univ. of Traditional Chinese Medicine's animal center animal use management regulations.
2.1.2 the preparation of medicine: get appropriate galangin and be dissolved in DMSO, be mixed with the mother solution of 0.1M, with normal saline dilution pneumoretroperitoneum drug administration by injection, concentration is 1mg/kg and 10mg/kg.
2.1.3 zoopery:
(1) 0.1M citric acid solution and citric acid three sodium solution are mixed with the ratio of 14:11, adjust mixed liquor PH to 4.3-4.5, stand-by.Take appropriate STZ powder, lucifuge is dissolved, and makes it the solution becoming 5.5mg/ml, and give the mouse peritoneal injection of fasting 12h immediately, 0.1ml/10g, the dosage finally giving STZ is 55mg/kg, successive administration 5 days.
(2) last administration one Zhou Houyong cuts tail method and surveys mouse blood sugar concentration, blood glucose value >=16.7mmol/L(250mg/dl) be considered as modeling success.Successful for modeling mice is divided at random 3 groups: DR model group (DR model group), galangin 1mg/kg group, galangin 10mg/kg group, often organizes 10.10 of non-i.p STZ normal C57 mices are as normal group (Control group) in addition.Within every two weeks, detect body weight change, monthly detect change of blood sugar.
(3) modeling success started administration after 2 months, lumbar injection, 0.1ml/10g, galangin 1mg/kg group, galangin 10mg/kg group give the galangin solution of variable concentrations respectively, and whole dosage is respectively: 1mg/kg, 10mg/kg, Model group gives the Vehicle controls of same volume, administration was put to death after 2 months, got retina and observed retinal neovascularization situation, and retina pathological section H & E dyes observation; Get serum and carry out Elisa experiment, detect the change of cytokine.
2.1.4 inner nuclear layer retina CD31 Immunofluorescence test galangin is to diabetic retinopathy mouse retinal angiogenesis treatment situation:
(1) retina is separated: taken off by the eyeball of putting to death rear mice, be fixed in 4% paraformaldehyde (in PBS), 4 DEG C are spent the night.By detachment of retina under anatomical lens, in PBS, omit rinsing 3-4 time.
(2) close: the retina after rinsing is put into Blocking Buffer(5%BSA is housed, 0.5%Trixton X-100inPBS) 1.5ml Epp pipe in, room temperature shaking table shakes slowly and hatches 3h.
(3) primary antibodie is hatched: be put in by the retina closed (antibody 1:200 dilutes, and antibody diluent is 1%BSA, 0.5%Trixton X-100in PBS) in CD31 primary antibodie reactant liquor, 4 DEG C of shaking tables shake slowly hatches 1-2 days.
(4) primary antibodie is washed: with Wash Buffer(0.5%Trixton X-100in PBS) at room temperature cleaning 6 times on shaking table, each 20min.
(5) two anti-hatch: enclosed by retina in the two anti-reactant liquors containing FITC conjugated anti-Rat IgG (1:200 dilution), room temperature lucifuge hatches 2h.
(6) wash two to resist: with Wash Buffer(0.5%Trixton X-100in PBS) at room temperature lucifuge cleans 6 times, each 20min on shaking table.
(7) mounting: be laid on microscope slide by retina under anatomical lens, cut off into petal-shaped, drips several anti-fluorescence quenchers, with Gelatin moutin solution(2g/ml Gelatin) mounting, covered.
(8) take pictures: take pictures under fluorescence microscope after retina immunofluorescence paving sheet is slightly dried, observe the newborn situation of retina medium vessels.
(9) vessel density counting: choose CD31 immunofluorescence photograph (200 ×), each group is selected 3-5 to open photo, calculates the number of blood vessel of optical center anyhow on axis of symmetry as vessel density.
2.1.5 VEGF assay in serum and vitreous chamber
(1) 50 μ l Assay Diluent RD1-41 are added at each Kong Zhonggang of enzyme mark version of VEGF antibody bag quilt, then 50 μ lStandard(totally 8 concentration are added respectively, be respectively 1000pg/ml, 500pg/ml, 250pg/ml, 125pg/ml, 62.5pg/ml, 31.2pg/ml), Control(Rat VEGF Kit Control) and sample.
(2) enzyme mark version is sealed with sealer, 500 ± 50rpm on horizontal shaker, incubated at room 2h.
(3) discard liquid in hole, fill it up with Wash Buffer and clean 5 times, for the last time Kong Zhongyu liquid is exhausted.
(4) every hole adds 100 μ l Rat VEGF Conjugate, and sealer, the same terms is in horizontal shaker incubated at room 1h.
(5) discard liquid in hole, fill it up with Wash Buffer and clean 5 times, for the last time Kong Zhongyu liquid is exhausted.
(6) every hole adds 100 μ l Substrate Solution(Color Reagents A:Color Reagents B=1:1), lucifuge hatches 30min.
(7) every hole adds 100 μ l Stop Solution, measures each hole absorbance at 450nm, 540nm place.
(8) according to the OD value of variable concentrations Standard, obtain mark bent, sample OD value is substituted into mark song, calculate VEGF content in hole.
2.1.6 statistical procedures
Experimental data all represents with meansigma methods ± standard error, and adopt SPSS11.5 statistical software to analyze, carry out variance analysis in One-WayANOVA mode, compare between two and adopt LSD method, P<0.05 is for having statistical significant difference standard.
2.2 experimental result
2.2.1 galangin is on the impact of blood glucose in diabetic mice and body weight
As seen from Table 4, each dosage group of galangin all can not improve alleviating of diabetic mice body weight, can not reduce the blood glucose of rising.Illustrate that galangin does not have clear improvement the drug activity of diabetes.
Table 4 galangin is on the impact of blood glucose in diabetic mice and body weight
* *p<0.001 and normal phase ratio
2.2.2 galangin is on the impact of diabetic mice retinal neovascularization
As seen from Figure 1, diabetic mice retina medium vessels is obviously newborn, and galangin each dosage group can obviously reduce amphiblestroid angiogenesis.
2.2.3 galangin is on the impact of VEGF content in diabetic mice serum and vitreous chamber
As seen from Figure 2, galangin can reduce the content of angiogenesis promoting factor Ⅴ EGF in serum and vitreous chamber by dose dependent.Prompting galangin can suppress the release of short Angiogenesis, suppresses amphiblestroid angiogenesis, thus improves diabetic retinopathy.
Embodiment 3 galangin improves the drug activity of the oxygen-induced retinopathy of oxygen induction
Retinopathy of prematurity (retinopathy of prematurity, ROP) has become a kind of disease of serious threat neonate vision health.Oxygen induction oxygen-induced retinopathy model (OIR) set up by Smith etc. successfully replicates the feature of retinopathy of prematurity (ROP), is used widely in ROP research.
3.1 materials and methods
3.1.1 animal: SPF level C57BL mouse, each 5 of male and female, 8 week age, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center (quality certification number: SCXK(Shanghai) 2012-0002).Raise in Shanghai Univ. of Traditional Chinese Medicine's animal experimental center, male and female random combine is 5 to breeding, and temperature 22 ± 1 DEG C, humidity 55 ± 5%, freely absorbs after feedstuff and water sterilization, 12 hours Dark-light cycle.Test and carry out in strict accordance with country and Shanghai Univ. of Traditional Chinese Medicine's animal center animal use management regulations.
3.1.2 the preparation of medicine: get appropriate galangin and be dissolved in DMSO, be mixed with the mother solution of 0.1M, with normal saline dilution pneumoretroperitoneum drug administration by injection, concentration is 20mg/kg.
3.1.3OIR model is set up: after C57BL mouse birth the 7th day (P7), be divided into normal group and anoxia group at random, often organize 10.Normal group Mouse feeder is in normal oxygen conditions; Anoxia group Mouse feeder is in 75.5% partial pressure of oxygen oxygen cabin, and namely oxygen environment is back in normal oxygen conditions on the 12nd day in 5 days afterwards, continues raising 5 days to the 17th day (P17), every day period intraperitoneal injection galangin 20mg/kg, successive administration 5 days.
3.1.4 retina immunofluorescence paving sheet: get P17 days sacrifice, win eyeball, in 4% paraformaldehyde (in PBS), 4 DEG C are fixedly spent the night, under anatomic microscope, cut off by iris scissors edge edge of cornea, remove crystalline lens and vitreous body, take out whole retina, PBS washes 2 ~ 3 times, Blocking Buffer(5%BSA, 0.5%Trixton X-100in PBS) close 2 hours, 2 days are hatched in 4 DEG C with CD31 antibody, Wash Buffer(0.5%Trixton X-100in PBS) wash 6 times, 2 hours are hatched with two anti-lucifuges, Wash Buffer washes 6 times, cut retina and become petal-shaped, be laid on microscope slide, the fixing also mounting of gelatin (2g/ml), take pictures in fluorescence microscopy Microscopic observation.
3.1.5 data analysis
Data result represents with means ± SE.Experimental data adopts SPASS16.0 software statistics, compares employing independent samples t test between two.Think during P<0.05 that there is statistical significant difference.
3.2 experimental result
Galangin is on the impact of oxygen induction neonatal mouse retinal angiogenesis
As seen from Figure 3, OIR model group Mouse Retina has a large amount of angiogenesis, and buckling of vessel distortion simultaneously forms a large amount of hemangioma (b), and after giving galangin, the blood vessel of hypertrophy obviously reduces, and hemangioma also reduces (c) to some extent.Prompting galangin can suppress OIR model group mouse retinal angiogenesis, thus improves retinopathy of prematurity.
Many aspects involved in the present invention have been done and have as above been set forth.It is to be understood, however, that put before not departing from spirit of the present invention, those skilled in the art can carry out equivalent change and modification to it, and described change and modification fall into the coverage of the application's claims equally.
Claims (9)
1. the application of galangin in preparation RF-6A inhibition of cell proliferation.
2. apply as claimed in claim 1, it is characterized in that, described RF-6A cell proliferation is induced by VEGF and is produced.
3. the application of galangin in the medicine of preparation control retina neovascular diseases.
4. the application of galangin in the medicine of preparation control diabetic retinopathy.
5. apply as claimed in claim 4, it is characterized in that, described diabetic retinopathy is that proliferating diabetic retinopathy becomes.
6. the application of galangin in the medicine of preparation control retinopathy of prematurity.
7. galangin is preparing the application prevented and treated in the medicine of age-related macular degeneration.
8. apply as claimed in claim 7, it is characterized in that, described age-related macular degeneration is wet age related macular degeneration.
9. can suppress a pharmaceutical composition for retinal neovascularization, it is characterized in that, it comprises the galangin for the treatment of effective dose.
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| CN106474101A (en) * | 2015-06-17 | 2017-03-08 | 海南医学院 | Application of the Galangin in treatment diabetes mellitus encephalopathy medicine |
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