CN106265626A - 7,8-dihydroxyflavones purposes in preparation treatment retinal degenerative disease medicine - Google Patents
7,8-dihydroxyflavones purposes in preparation treatment retinal degenerative disease medicine Download PDFInfo
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- CN106265626A CN106265626A CN201510252462.7A CN201510252462A CN106265626A CN 106265626 A CN106265626 A CN 106265626A CN 201510252462 A CN201510252462 A CN 201510252462A CN 106265626 A CN106265626 A CN 106265626A
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Abstract
The invention belongs to pharmaceutical field, relate to 7,8-dihydroxyflavone purposes in preparation treatment retinal degenerative disease medicine.The present invention passes through adult SD rats contusion of optic nerve model experiment, and result shows 7, and 8-dihydroxyflavone can reduce the apoptosis of retinal ganglial cells, improves survival rate, compromised retinal neuron is had significant protective effect；The 7 of the present invention; 8-dihydroxyflavone treats retinal degenerative disease further by protection compromised retinal neuron, and described retinal degenerative disease includes: glaucoma, degeneration of macula, retinitis pigmentosa, ischemic optic neuropathy, traumatic contusion of optic nerve.Present invention also offers 7,8-dihydroxyflavone, as the new small molecule pharmaceutical preparation of main active, uses topical in eye vitreous chamber mode, compromised retinal neuron can be produced significant protective effect.
Description
Technical field
The invention belongs to pharmaceutical field, relate to 7, the 8-dihydroxyflavone new purposes in pharmacy, it is specifically related to 7,
8-dihydroxyflavone purposes in treatment retinal degenerative disease protection medicine.
Background technology
Prior art discloses retinal neurons apoptosis and axonal degeneration is glaucoma, age-related macular degeneration, regards
The common pathologic basis of the retinal degenerative disease such as retinal pigment degeneration.Irreversibility as No. 1 in the world
Blinding oculopathy, such as: glaucoma loses with Progressive symmetric erythrokeratodermia retinal ganglial cells and axonal degeneration is characterized,
Clinical manifestation is typical neuratrophia and defect of visual field.At present, main to the treatment of glaucoma in clinical practice
Intraocular pressure is reduced with the method for medicine or operation, but although quite a few patient's intraocular pressure controls satisfied, but regard merit
Can still there is continuation corruptions, trace sth. to its source, be the Pathologic niche sustainable existence owing to there is apoptosis, depending on
Nethike embrane neuron can not effective regeneration so that neuronal quantity constantly reduces, and causes visual function Progressive symmetric erythrokeratodermia to decline；
Known in the industry, owing to the airtight spheroid anatomical structure of eyeball makes external ocular drop be unable to reach fundus tissue,
And the existence of blood retina barrier makes the medicine of Formulations for systemic administration be unable to reach valid density at fundus tissue, this enters
One step adds the treatment difficulty of this type of disease.
7,8-dihydroxyflavones (Dihydroxyflavone, DHF) belong to flavone derivative, and its height selects
Property TfkB agonist, molecular weight 254.24Da；
Up to now, there is not yet relevant 7, the report of 8-dihydroxyflavone treatment retinal degenerative disease.
Present inventor intends providing the medicine of new treatment retinal degenerative disease, is provided in particular in 7,8-
The dihydroxyflavone protective effect to the retinal neurons of damage.
Summary of the invention
It is an object of the invention to provide 7,8-dihydroxyflavone new application in pharmacy, it is specifically related to 7,8-dihydroxy
Base flavone purposes in preparation treatment retinal degenerative disease medicine.
The molecular formula of heretofore described 7,8-dihydroxyflavone is C15H10O4, molecular weight is 254.24Da.
The present invention based on TfkB be present in retinal ganglial cells, M ü ller cell, amacrine cell,
With in each confluent monolayer cells of retina such as cone cell, 7 described in employing, 8-dihydroxyflavone adult SD rats regards god
Being tested through contusion models, result shows, described 7, and 8-dihydroxyflavone activates highly selectively
TfkB, is combined with TfkB extracellular space, causes Receptor dimerization, autophosphorylation, and energy
Activate downstream AKT, ERK signal path；And be combined with ligands specific, play promotion cell survival and resist
Apoptotic effect, has protective effect to the retinal neurons of damage.
More specifically, the present invention passes through single intravitreal 7, and 8-dihydroxyflavone carries out big to Adult SD
The protective effect experiment of Mus compromised retinal ganglionic cell, result shows, compared with not treating group, 7,8-bis-
Flavonol can significantly improve compromised retinal Ganglion Cell Survival rate, has significant Neuroprotective effect,
Contusion of optic nerve adult SD rats retinal ganglial cells is had significantly by described 7,8-dihydroxyflavone
Protective effect.
In the present invention, use the ripe contusion of optic nerve animal model that this area is generally admitted, can be effectively
Cause retinal ganglial cells, M ü ller cell, amacrine the minimizing of interior neuronal quantity, god
Thinning through fiber layer thickness, cause the change of visual evoked potential；Experimental result show that, on DiI
Mound inverse mark RGCs finds, 7,8-dihydroxyflavone treatment groups and do not treat between group, the quantity of the RGCs of survival
There is significant difference；TUNEL detection finds that 7,8-dihydroxyflavone can significantly reduce the apoptosis rate of RGCs；
GFAP immunofluorescence dyeing finds that 7,8-dihydroxyflavone can substantially reduce the expression of GFAP.
The 7 of the present invention, 8-dihydroxyflavone can be prepared the medicine for the treatment of retinal degenerative disease, be used for protecting
Compromised retinal neuron treats retinal degenerative disease further, and described retinal degenerative disease includes:
Glaucoma, degeneration of macula, retinitis pigmentosa, ischemic optic neuropathy, traumatic contusion of optic nerve.
Further, the present invention provides a kind of new small molecule medicine system for treating retinal degenerative disease
Agent；Wherein 7,8-dihydroxyflavone is as main active, and during use, by 7,8-dihydroxyflavone local is given
Medicine is in eye vitreous chamber, in particular by the administering mode of vitreous body of eye chamber local injection, can regard impaired
Nethike embrane neuron produces significant protective effect.
Accompanying drawing explanation
Fig. 1, after contusion of optic nerve, the RGCs density of each group survival in 1 week compares, wherein, * * represent with
0.1%DMSO group is compared, P < 0.001.
Fig. 2, after contusion of optic nerve 1 day, each comparison organizing RGCs apoptosis rate；Wherein, * represents and 0.1%DMSO
Group is compared, P < 0.005.
Fig. 3, after contusion of optic nerve 3 days, each comparison organizing RGCs apoptosis rate；Wherein, 5uM 7,8-DHF
Group, BDNF group have significant difference, P value < 0.05 compared with 0.1%DMSO group.
Fig. 4, after contusion of optic nerve 7 days, each comparison organizing RGCs apoptosis rate；Wherein, * * represents and 0.1%DMSO
Group is compared, P < 0.001.
Fig. 5, after contusion of optic nerve, different time points respectively organizes retinal slice ganglion cell layer apoptosis feelings
Condition compares.
Fig. 6, after contusion of optic nerve 1 day, each group retina GFAP expression compared；Wherein, * represents
Compared with 0.1%DMSO group, P < 0.005.
Fig. 7, contusion of optic nerve 3 days, each group retina GFAP expression compares；Wherein, * * represent with
0.1%DMSO group is compared, P < 0.001.
Fig. 8, contusion of optic nerve 7 days, each group retina GFAP expression compares；Wherein, * * represent with
0.1%DMSO group is compared, P < 0.001.
Detailed description of the invention
Hereinafter embodiments of the invention are elaborated: following example are being front with technical solution of the present invention
Put and implement, give detailed embodiment and process, but protection scope of the present invention is not limited to following
Embodiment.
Embodiment 1:DiI inverse mark cell counting detection 7,8-dihydroxyflavone is thin to compromised retinal neuroganglion
The protective effect experiment of born of the same parents (RGCs)
1. experimental subject and packet
Experimental subject: adult male SD rats (about 200g)；
It is randomly divided into experimental group, negative control group, positive controls (n=5)；Experimental group is divided into again 4 Asias
Group, respectively through tetra-concentration 7 of intravitreal 1uM, 5uM, 10uM, 20uM, 8-DHF 4uL,
Negative control group intravitreal 0.1%DMSO solution 4uL, positive controls intravitreal
0.5ug/uL BDNF 4uL；
Brain Derived Neurotrophic Factor (Brain-Derived Neurotrophic Factor, BDNF) has aobvious
The retinal neurons protected effect write, confirms BDNF in the several animal models such as contusion of optic nerve, cross-section wound
Retinal ganglial cells (RGCs) can be protected, promote survival and axon regeneration, and this protective effect
It is by specific binding TfkB, activates what downstream signaling pathway realized, BDNF the most in this experiment
As positive control medicine；
Before all operation techniques, laboratory animal all gives xylazine (8mg/kg) and ketamine
(60mg/kg) intramuscular injection induced anesthesia, without there is rat anesthesia lethal cases in operation process, anesthesia is clear
Put back to Animal House after Xinging to raise；
2. superior colliculus retrograde labeled surviving retinal ganglion cell: be fixed on brain after adult SD rats anesthesia
On the stereotaxic instrument headstock, the skin cutting head exposes skull, in bilateral superior colliculus corresponding position apertured,
1.2mm, forward 2.0mm position is opened by posterior, (double with microsyringe depth of needle 3.2mm injection DiI
The each 5ul in side), scalp suture is coated with antibiotic；
3. contusion of optic nerve Animal Model and administration: after DiI superior colliculus retrograde labeled the 5th day, uses chlorine ammonia
After ketone (80mg/kg) and xylazine (12mg/kg) lumbar injection general anesthesia, SD rat left eye week office
Portion's cleaning-sterilizing, goes in ring and cuts off outer canthus portion bulbar conjunctiva, open Tenon ' s capsule, blunt separation Suspensory ligament, cruelly
Dew optic nerve, with microhemostat, holding force is 70g, clamps optic nerve 15 seconds after ball at about 2mm
Causing optic nerve injury, stitch ball conjunctiva, Ofloxacin salve is coated with eye；Marcus-gun occurred in postoperative 2nd day
Pupil, eyeball is without the most prominent, and optical fundus is model success without bleeder；Right eye is not performed the operation as normal control；
After optic nerve injury, experimental group through intravitreal variable concentrations 7,8-DHF 4uL (1uM, 5uM, 10uM,
20uM), negative control group intravitreal 0.1%DMSO solution 4uL, positive controls injection 0.5ug/uL
BDNF 4uL.Postoperative at that time and postoperative under 1 day operating microscope observe, do not occur intraocular hemorrhage and
Turn white cataract, intraocular infection etc., includes experiment in；
4. inner nuclear layer retina retinal ganglial cells counting: postoperative 1 week, use normal saline 200-250ml,
4% paraformaldehyde 200ml, through heart filling point dead SD rat, takes out right eye eyeball, by eyeball in 4% poly
Formaldehyde soaks and fixes 2 hours, then eyeball is placed in 0.01M PBS solution, after corpus ciliare, cut off eye
Ball removes anterior ocular segment and vitreous body, peels off retina, retina is cut off pintongs, is laid on microscope slide, uses
Mountant mounting without DAPI, fluorescence microscopy Microscopic observation carries out RGCs counting；Method of counting is as follows:
Four, upper and lower, left and right quadrant is from depending on (representing central retina, pars intermedia away from nipple 1mm, 2mm, 3mm
Retina, peripheral retina) one 200 times of fluorescence photo of each bat, artificial double blinding counts every photo DiI
Positive RGCs quantity, calculates full retina average RGCs density (individual/mm2)；
5. experimental result shows, the average density of normal SD rats RGCs is 1782.4 ± 106.11/mm2；
After contusion of optic nerve 1 week, the density of negative control group RGCs substantially reduces, and drops to 824.6 ± 50.77
/mm2, experimental group each subgroup (1uM, 5uM, 10uM, 20uM) RGCs average density is respectively 1019.2
± 84.45/mm2, 1277.4 ± 65.89/mm2, 1219.6 ± 103.74/mm2And 1205.4
± 67.65/mm2, BDNF group RGCs average density is 1288.6 ± 114.61/mm2, each experimental group
Significant difference (p < 0.05) is all had compared with negative control group with BDNF group；Wherein 5uM, 10uM, 20uM
7,8-DHF concentration groups and BDNF group, these four groups have notable significant difference with negative control group RGCs quantity
(p<0.001), and 5uM, 10uM, 20uM, this four group differences not statistically significant (p>0.05) of BDNF；
Test result indicate that, single vitreous chamber 7,8-dihydroxyflavone intervention has treatment to impaired RGC,
Protected effect.
Embodiment 2 apoptosis In situ cell apoptosis detection method (TUNEL detection) observes 7,8-dihydroxyflavone pair
The anti-apoptotic test of compromised retinal ganglionic cell (RGCs)
1. experimental subject and packet
Experimental subject: adult male SD rats (about 200g)；
It is randomly divided into experimental group, negative control group, positive controls (n=3).Experimental group is noted through vitreous chamber
Penetrate 5uM concentration 7,8-DHF 4uL, negative control group intravitreal 0.1%DMSO solution 4uL, the positive
Matched group intravitreal 0.5ug/uL BDNF 4uL；
2. contusion of optic nerve Animal Model and administration: chlore-ammonia ketone (80mg/kg) and xylazine (12
Mg/kg) after lumbar injection general anesthesia, SD rat left eye week local cleaning-sterilizing, go in ring cut off outer canthus portion
Bulbar conjunctiva, opens Tenon ' s capsule, blunt separation Suspensory ligament, exposes optic nerve, with microhemostat, hold
Power is 70g, clamps optic nerve and within 15 seconds, cause optic nerve injury after ball at about 2mm, stitch ball conjunctiva,
Ofloxacin salve is coated with eye；Within postoperative 2nd day, Marcus-gun pupil occur, eyeball highlights without obvious, optical fundus
It is model success without bleeder.Right eye is not performed the operation as normal control.After optic nerve injury, experimental group is through glass
Body cavity injection 5uM concentration 7,8-DHF 4uL, negative control group intravitreal 0.1%DMSO solution 4uL,
Positive controls injection 0.5ug/uL BDNF 4uL；Postoperative at that time and postoperative under 1 day operating microscope see
Examine, intraocular hemorrhage, complicated cataract, intraocular infection etc. do not occur, includes experiment in；
3. retinal slice In situ cell apoptosis detection: postoperative 1,3,7 days with normal saline 200～250mL,
4% paraformaldehyde 200mL takes out eyeball after heart perfusion is fixing, by eyeball in 4% paraformaldehyde after
Fix 2 hours, successively in 20% sucrose, 30% sucrose soaked overnight, cut off cornea along limbus of corneae, remove
Crystal and vitreous body.Fill up eyeball with OCT embedding medium, make continuous frozen section, thickness along eyeball sagittal plane
10μm.In situ cell apoptosis detection uses In situ cell apoptosis detection method (TUNEL staining).Frozen section
Room temperature is dried, and after the fixing 20min of 4% paraformaldehyde 15-20 DEG C, 0.01M PBS rinses 30min,
Delay liquid with freshly prepared rush liquid 4 DEG C immersion 2min containing 0.1%Triton X-100,0.1% sodium citrate again,
0.01M PBS rinses 2min, rinses 2 times.After dry specimen periphery microscope slide, dropping TUNEL mixing is anti-
Answering liquid, at 37 DEG C, 60min, 0.01M PBS rinses 2min, rinses 3 times.Add the mountant containing DAPI
Carry out mounting.Fluorescence microscope；
4. result shows: normal SD rats ganglion cell layer of retina has no apoptotic cell, and TUNEL dyes
Negative；After contusion of optic nerve 1 day, all visible apoptotic cell of each group ganglion cell layer of retina, wherein negative
Matched group RGCs apoptosis rate is 5.59%, and 5uM 7,8-DHF concentration group ganglion cell's apoptosis rate is 2.065%, BDNF
Group apoptosis rate is 1.46%, and latter two groups all have significant difference (P value < 0.005) compared with negative control group；
Dampen latter 3 days each group ganglion cell layer apoptosis rates all to increase, wherein 0.1%DMSO group RGCs apoptosis
Rate is 12.29%, and 5uM 7,8-DHF concentration group RGCs apoptosis rate is 7.57%, and BDNF group is 5.341%, after
Two groups have significant difference (P value < 0.05) compared with 0.1%DMSO group；Dampen latter 7 days and respectively organize nerve
Ganglion cell's apoptosis rate persistently rises, and 0.1%DMSO group RGCs apoptosis rate reaches 33.11%, 5uM 7,8-DHF group
It is respectively 11.7% and 9.70%, 5uM 7,8-DHF group and BDNF group and 0.1% with BDNF group RGCs apoptosis rate
DMSO group is compared has notable significant difference (P value < 0.001), and the notable (P of this two group difference
Value > 0.05)；
Within after contusion of optic nerve 1 day, rising, each group all there is TUNEL positive cell, and apoptosis rate presents increasing in time
The trend added.After contusion of optic nerve 7 days, relative to 5uM 7,8-DHF and BDNF group, negative control group god
More significantly through the apoptosis rate of ganglion cell, difference tool is statistically significant, P value < 0.001, and 5uM
Between 7,8-DHF and BDNF groups apoptosis rate at each time point all without difference statistically, P value > 0.05；
Result shows 7, and 8-dihydroxyflavone has notable protective effect, protected effect and BDNF to impaired RGCs
Albumen is with effect.
It is thin to compromised retinal neuroganglion that 7,8-dihydroxyflavone is observed in the detection of embodiment 3GFAP SABC
The maintenance microenvironment effect test of born of the same parents (RGCs)
Glial fibrillary acidic protein (Glial fibrillary acidic protein, GFAP) is a kind of kytoplasm
Interior silk-like proteins, is present in the glial cell that central nervous system is different, is the finger of reflection extracellular microenvironment
Mark, research shows, it is the non-specific labelling that central nervous system sustains damage that GFAP expresses rising, and glue
The activation of cell plastid is one of major reasons of optic nerve disease RGCs loss such as glaucoma, in the present embodiment,
After contusion of optic nerve 1 day, 3 days, 7 days, each group of retinal slice GFAP expression is exempted from
Epidemic disease groupization detects, semi-quantitative analysis, is indirectly reflected by the difference of GFAP expression between each group of contrast
The 7,8-DHF protective effect to retinal ganglial cells；
1. experimental subject and packet
Experimental subject: adult male SD rats (about 200g),
It is randomly divided into experimental group, negative control group, positive controls (n=3).Experimental group is noted through vitreous chamber
Penetrate 5uM concentration 7,8-DHF 4uL, negative control group intravitreal 0.1%DMSO solution 4uL, the positive
Matched group intravitreal 0.5ug/uL BDNF 4u；
2. Animal Model and administration: chlore-ammonia ketone (80mg/kg) and xylazine (12mg/kg) abdominal cavity
Injection general anesthesia after, SD rat left eye week local cleaning-sterilizing, go in ring cut off outer canthus portion bulbar conjunctiva, open
Tenon ' s capsule, blunt separation Suspensory ligament, forward tractive eyeball, expose optic nerve, with microhemostat, hold
Power is 70g, clamps optic nerve and within 15 seconds, cause optic nerve injury after ball at about 2mm, stitch ball conjunctiva,
Ofloxacin salve is coated with eye；Within postoperative 2nd day, Marcus-gun pupil occur, eyeball highlights without obvious, optical fundus
It is model success without bleeder；Right eye is not performed the operation as normal control；After optic nerve injury, experimental group is through glass
Body cavity injection 5uM concentration 7,8-DHF 4uL, negative control group intravitreal 0.1%DMSO solution 4uL,
Positive controls injection 0.5ug/uL BDNF 4uL.Postoperative at that time and postoperative under 1 day operating microscope see
Examine, intraocular hemorrhage, complicated cataract, intraocular infection etc. do not occur, includes experiment in；
3. immunohistochemical staining retina GFAP expression: use normal saline in postoperative 1,3,7 days
200-250mL, 4% paraformaldehyde 20OmL, through heart filling point dead SD rat, take out eyeball, by eyeball in 4% poly
Formaldehyde soaks and fixes 2 hours, then by eyeball successively in 20% sucrose, 30% sucrose soaked overnight, after corpus ciliare
Cut off eyeball and remove anterior ocular segment and vitreous body；Fill up eyeball with OCT embedding medium, make along eyeball sagittal plane the most freezing
Section, thickness 10uM；Frozen section room temperature is dried 2 hours, rinses 5min with 0.01M PBS, then with fresh
Preparation soak 5min containing 0.01%twean20, then by 0.3%Triton X-100 soaking at room temperature 10min,
With mounting 1 hour under confining liquid room temperature, blot slide, add little mouse-anti GFAP antibody (1:100 dilution),
Ambient temperatare put 24 hours overnight, with 0.01M PBS rinse 3 times, each 5min.After blotting slide, add mountain
Goat anti-mouse igg 488 (1:200 dilution), ambient temperatare is put 1 hour, 0.01M PBS flushing 3 times, every time
5min.Add the mountant containing DAPI and carry out mounting.Fluorescence microscope；
4. result shows: dye with a small amount of GFAP seen from nerve fibre layer under normal SD rats inner limiting membrane
The positive, GFAP expression rate is 5.30 ± 1.25%, and each layer of remaining retina has no positive GFAP coloring；Depending on god
Within 1 day after dampening, respectively group retinal nerve fibre layer and ganglion-cell layer have the GFAP positive staining increased, wherein
0.1%DMSO group GFAP expression rate is 11.28 ± 1.31%, and 5uM 7,8-DHF group is 10.0 ± 0.51%, BDNF
Group is 7.93 ± 0.86%, all has significant difference (P value < 0.05) compared with normal group, and BDNF group with
0.1%DMSO group is compared has notable significant difference (P value < 0.005)；Dampen latter 3 days, 0.1%DMSO
Group, 5uM 7,8-DHF group, BDNF group retina GFAP dye intensification, except retinal nerve fibre layer and
Outside ganglion-cell layer, interior from shape layer, inner nuclear layer object line strip GFAP dyeing, each group GFAP expression rate is respectively
17.5 ± 0.94%, 11.0 ± 2.19%, 10.16 ± 0.85%, negative control group is compared with latter two groups, and difference has
Be statistically significant (P value < 0.001)；Dampening latter 7 days, each group retina GFAP dyeing is further
Deepening, intensive, 0.1%DMSO group GFAP expression rate is 24.67 ± 1.32%, and 5uM 7,8-DHF group is 14.48
± 0.58%, BDNF group is 13.4 ± 1.36%, and wherein, 5uM 7,8-DHF group, BDNF group coloring degree are low
In negative control group, difference tool is statistically significant (P value < 0.001)；
Test result indicate that, after contusion of optic nerve 1 day, each experimental group GFAP expresses increase, with normal group phase
More statistically significant than difference (P value < 0.05)；After contusion of optic nerve the 3rd day, the 7th day, 5uM 7,8-DHF
Group and BDNF group GFAP expression are substantially less than negative control group (P value < 0.001), and 5uM 7,8-DHF
GFAP expression no significant difference between group and BDNF two groups (P value > 0.05)；
The present invention, by respectively organizing the difference of GFAP expression, is further characterized by described 7,8-DHF pair
Damage retinal neurons has protected effect.
Claims (5)
1.7,8-dihydroxyflavone is for preparing the purposes in treatment retinal degenerative disease medicine；Described
The molecular formula of 7,8-dihydroxyflavone be C15H10O4, molecular weight is 254.24Da.
Purposes the most according to claim 1, it is characterised in that described retinal degenerative disease is
Glaucoma, degeneration of macula, retinitis pigmentosa, ischemic optic neuropathy or traumatic contusion of optic nerve.
3. the small molecule drug formulation being used for treating retinal degenerative disease, it is characterised in that wherein
Using 7,8-dihydroxyflavone as main active.
Small molecule drug formulation the most according to claim 3；It is characterized in that, described pharmaceutical preparation
Topical is used to use in eye vitreous chamber.
Small molecule drug formulation the most according to claim 3；It is characterized in that, described pharmaceutical preparation
The administering mode using vitreous body of eye chamber local injection uses.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014100433A1 (en) * | 2012-12-19 | 2014-06-26 | Brown University | Methods for treatment of microcephaly associated autism disorders |
| CN104622867A (en) * | 2013-11-12 | 2015-05-20 | 广州康睿生物医药科技有限公司 | Uses of 7,8-dihydroxyflavone in preparation of drugs for treatment of optic nerve injury |
-
2015
- 2015-05-18 CN CN201510252462.7A patent/CN106265626A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014100433A1 (en) * | 2012-12-19 | 2014-06-26 | Brown University | Methods for treatment of microcephaly associated autism disorders |
| CN104622867A (en) * | 2013-11-12 | 2015-05-20 | 广州康睿生物医药科技有限公司 | Uses of 7,8-dihydroxyflavone in preparation of drugs for treatment of optic nerve injury |
Non-Patent Citations (2)
| Title |
|---|
| SUNG-WUK JANG ET AL.: "A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone", 《PNAS》 * |
| VIVEK K. GUPTA ET AL.: "Protective Effects of 7,8-Dihydroxyflavone on Retinal Ganglion and RGC-5 Cells Against Excitotoxic and Oxidative Stress", 《J MOL NEUROSCI》 * |
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