CN105687168A - Application of resveratrol in preparation of antidepressant - Google Patents
Application of resveratrol in preparation of antidepressant Download PDFInfo
- Publication number
- CN105687168A CN105687168A CN201610049980.3A CN201610049980A CN105687168A CN 105687168 A CN105687168 A CN 105687168A CN 201610049980 A CN201610049980 A CN 201610049980A CN 105687168 A CN105687168 A CN 105687168A
- Authority
- CN
- China
- Prior art keywords
- resveratrol
- depression
- mice
- test
- antidepressant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
Abstract
The invention relates to application of resveratrol in preparation of an antidepressant, and belongs to the field of medicament. A mouse depression model is built through chronic mild stress stimulation, the resveratrol is forcedly fed and given to a mouse, the anti-depression activity of the resveratrol is evaluated through a beginning activity test, an elevated plus maze test, a social interference test, a forced swimming test and a tail suspension test, and possible mechanism of the resveratrol is detected through molecular biology and electron microscopy. A result shows that the resveratrol can be used for reversing behavioral manifestations, such as fatigue, depression and decreased social ability, which accompany depression, the behavioral manifestations accompany increment of hippocampus SIRT1 (Silent Information Regulator Factor 1) and PGC (Primordial Germ Cell)-1 alpha protein expression and improvement of the integrity of a hippocampal myelin film structure of the mouse, the destroy which is induced by the depression on the integrity of the hippocampal myelin film structure disappears, the resveratrol is capable of increasing the expression of antioxidant enzyme through activating an SIRT1/PGC-1 alpha/PPARr (Peroxisome Proliferator-activated Receptor) signal channel, the integrity of the hippocampal myelin film structure is protected, and the stress-induced depression is reduced.
Description
Technical field
The present invention relates to the application in preparing antidepressant drug of a kind of resveratrol, belong to field of medicaments。
Background technology
Resveratrol (2; 3; 4'-trihydroxystilbene) (Resveratrol; RSV) as a kind of natural Polyphenols complex; being mainly derived from the plants such as Fructus Vitis viniferae, Rhizoma Polygoni Cuspidati, Semen arachidis hypogaeae, Fructus Mori, resveratrol obtains the extensive concern of scientist the earliest and comes from antioxidation vinous, antitumor and cardiovascular protective effect；2003, researcher confirmed SIRT1 anakmetomeres 21 kinds same in the screening micromolecular activator of SIRT1, and wherein resveratrol has been widely recognized with its strong non-oxidizability。
Existing bibliographical information, resveratrol adds saccharomyces cerevisiae in the way of activating SIRT1, the life cycle of Caenorhabditis elegans and Drosophila melanogaster, improve rodent metabolism and cardiovascular function, decrease the steatosis of liver, reduce inflammatory reaction, improve endurance (BargerJL, KayoT, PughTD, ProllaTA, WeindruchR. (2008) Short-termconsumptionofaresveratrol-containingnuraceutic almixturemimicsgeneexpressionoflong-termcaloricrestricti oninmouseheart.ExpGerontol.43:859-866.)；Research display resveratrol is closely related with many Nervous and mental diseases, by promoting mitochondrial increment, generation (the PasinettiGM of activation SIRT1 and then suppression Alzheimer, WangJ, HoL, ZhaoW, DubnerL. (2015) Rolesofresveratrolandothergrape-derivedpolyphenolsinAlzh eimer'sdiseasepreventionandtreatment.BiochimBiophysActa. 1852:1202-1208.), also there is bibliographical information resveratrol to neuronic survival, differentiation, growth promoter plays an important role, (DexiangL, KaiX, XudongY, JianhuaG, LiG, etal. (2014) Resveratrolreversestheeffectsofchronicunpredictablemilds tressonbehavior, serumcorticosteronelevelsandBDNFexpressioninrats.BehavBr ainRes268:1-7), by suppressing hpa axis, and then promote damaged neuron regeneration。But whether resveratrol can activate SIRT1 signal path, gene expression relevant with oxygen metabolism in the short mitochondrial activation and proliferation of regulation and control and mitochondrion, play antidepressant activity and be but rarely reported；The present invention have studied the antidepressant activity of resveratrol and the Molecular Biology Mechanism thereof。
Summary of the invention
It is an object of the invention to overcome the vacancy in prior art, resveratrol antidepressant applied, the using value new for resveratrol contributes, and provides experiment basis to the industrialization development of resveratrol。
The present invention provides resveratrol application in preparing antidepressant drug。
Wherein, described antidepressant sample behavior is degradation under fatigue, anxiety, depression and social contact ability。
The present invention first passes through chronic gentle stress stimulation and sets up mice depression model, raise by force and give resveratrol three weeks, pass through open field test, elevated plus-maze test, social interference experiment, forced swim test and tail-suspention test evaluate its antidepressant activity, by the change of immunofluorescence and WesternBlotting technology for detection hippocampal tissue SIRT1 and PGC-1 α protein expression and Hippocampus myelin membrane structure, to inquire into its mechanism of action。Result display resveratrol significantly increases the body weight of depression mice, decreases the set time of mouse forced swimming test, tail-suspention test。Reducing the society attack time of interference experiment, number of times, increase its interference time, number of times, namely resveratrol has the activity of depression。Resveratrol can inducing mouse hippocampal tissue SIRT1 and PGC-1 α protein expression and improve the ultrastructure of Hippocampus myelin, the infringement of Hippocampus myelin thousand film structure of depression induction disappears, the above results illustrates: resveratrol may be by activation SIRT1/PGC-1 α/PPARr signal path, decrease the destruction of the Hippocampus sheath structure of stress-induced, play antidepressant effect。
The present invention also provides for a kind of antidepressant medicine, and described pharmaceutical pack can be made up of resveratrol and pharmaceutically acceptable carrier containing resveratrol or described medicine。
Described medicine is resveratrol is single active drug composition or the compound recipe form formed with other ingredients with similar effect。
Beneficial effects of the present invention:
The present invention demonstrates resveratrol by series of experiments and has antidepressant activity；Its biologic activity, mainly through raising SIRT1 and PGC-1 α protein expression, activates SIRT1/PGC-1 α/PPARr signal path, and then promotes neuronic survival, and form occurs, the function of synapse and increase neuronic plasticity, plays antidepressant effect。
Although behavioristics's presentation of depression is difficult to evaluate, but the Behaviors survey of some classics such as forced swim test, tail-suspention test have proven to a kind of effective means evaluating depression, resveratrol can substantially reduce the invasion time rate of mice society interference experiment, invasion time digit rate, dramatically increase time and the number of times of mice society interference experiment, namely resveratrol significantly increases social contact ability, decreases society's aggressive behavior simultaneously。
Additionally, resveratrol can reduce the set time of mouse forced swimming test, increasing its swimming time, prompting resveratrol can significantly reduce depressive symptom；And above-mentioned behavioristics's performance is with the change of mice prologue behavior autonomic activities speed, distance, making the veratryl alcohol impact on above-mentioned Behaviors survey result clear is not because changing mice behavior baseline generally, causes mice depressed。
At present, the medicine overwhelming majority of depression passes through chemosynthesis, prolonged application brings many toxic and side effects to body, therefore, the natural product having antidepressant function and having no side effect is found in an urgent demand, resveratrol has been proved to be able to regulate hypothalmus-pituitary-adrenal axis and monoaminergic system and antagonism is cognitive and anxiety dysfunction, therefore, will have broad application prospects with natural product-resveratrol antagonism depression。
Accompanying drawing explanation
Fig. 1: the resveratrol impact on depression Mouse Weight；In figure, illustration is four groups of mices average weight of 6 weeks。
Fig. 2: the resveratrol impact on the prologue behavior of depression mice；In figure, left figure is the impact of move distance, and right figure is the impact of frequency of standing；
Fig. 3: resveratrol is on depression mice society interference experiment: the impact of interaction time (A), interactive number of times (B), attack time (C) and number of times of attack (D)；
Fig. 4: the resveratrol impact on the depression mouse forced swimming test set time；
Fig. 5: the resveratrol impact on the depression Tail suspension test set time；
Fig. 6: the WesternBlot detection resveratrol impact on depression mice PGC-1 α protein expression；In figure, upper figure is WesternBlotting experimental result；Figure below is mice PGC-1 α protein expression result。
Fig. 7: the Immunofluorescence test resveratrol impact on depression mice SIRT1 protein expression；In figure, A. matched group, B. resveratrol group, the chronic gentle stress group of C., the chronic gentleness of D. stress+resveratrol group；1 represents nucleus, and 2 for measuring albumen, and 3 is the picture after merging, and in figure, scale size is 50 μm。
Fig. 8: the Immunofluorescence test resveratrol impact on depression mice PGC-1 α protein expression；In figure, A. matched group, B. resveratrol group, the chronic gentle stress group of C., the chronic gentleness of D. stress+resveratrol group；1 is nucleus, and 2 for measuring albumen, and 3 is the picture after merging, and in figure, scale size is 50 μm。
Fig. 9: the resveratrol impact on depression hippocampus of mice myelin membrane structure；In figure, A. matched group, the chronic gentle stress group of B., C. resveratrol group, the chronic gentleness of D. stress+resveratrol group, in figure, scale size is 500nm。
Detailed description of the invention
Embodiment 1: the foundation of depression model
Chronic gentle stress stimulation (Chronicmildstress, CMS)) within three weeks, setting up mice depression model, chronic gentle stress stimulation is followed following experimental technique and is carried out: mice is exposed under different irritability stimulations: food deprivation, water deprivation, cage tilts, moist bedding and padding, food limits, Restraint Stress, these irritability stimulates give once every day, random two kinds, continuous three weeks, matched group was without any stress stimulation。
Embodiment 2: Behaviors survey
C57BL/6J male mice is purchased from Jiangsu University's Experimental Animal Center, 10-12 week old, individually feed in temperature (22 ± 1 DEG C), humidity (55 ± 5%), the indoor of 12h illumination/12h night (light application time 07:30AM-19:30PM), sufficient water and provand, experiment is divided into four groups, often group 8: 1. matched group (normal saline): be not exposed to chronic gentleness stress+saline therapy group；2. resveratrol group: being not exposed to chronic gentleness stress+RSV treatment group；3. model group (chronic gentle stress group): be exposed to chronic gentleness stress+saline therapy group；4. model+resveratrol group (chronic gentleness stress+resveratrol group): being exposed to chronic gentleness stress+RSV treatment group。Resveratrol (is purchased from Aladdin reagent, Chinese Shanghai) dosage 200mg/kg, is administered volume 10mL/kg, saline administration volume 10mL/kg；It is administered every day 1 time (08:00AM), successive administration 3 weeks, starts Behaviors survey from the 22nd day (after administration 1h) of administration。
Behavior test carries out according to following order: prologue active experiment, elevated plus-maze test, social interference experiment, forced swim test and tail-suspention test。
(1) body weight
Mouse Weight is monitored once every day, with cycle for abscissa, average weight in one week is mapped as vertical coordinate, and result shows: the body weight of the depression model group mice of chronic gentle stress-induced is decreased obviously, and the use of resveratrol makes the body weight of depression mice significantly increase (see figure 1)。
(2) open field test
Mice is placed in the transparent automatic movable monitor of a 50cm × 25cm × 20cm (OptoM3, ColumbusInstruments, Columbus, OH)。The every 10min of infrared observation records 1 time, continuously movable 6 times of record mice prologue, altogether 60min, and after having tested, mice is sent to return in rearging cage, and cleans monitor with the ethanol of 10%。Prologue autonomic activities experimental result is shown in Fig. 2, and resveratrol does not affect mice autonomic activities time, speed and distance, and namely resveratrol does not cause the change of mice behavior baseline。
(3) Elevated plus-maze test (EPM)
Elevated plus-maze test carries out (ZhangW.N. with reference to this laboratory conventional method, BastT, XuY, FeldonJ. (2014) Temporaryinhibitionofdorsalorventralhippocampusbymuscimo l:Distincteffectsonmeasuresofinnateanxietyontheelevatedp lusmaze, butsimilardisruptionofcontextualfearconditioning.BehavBr ainRes.262:47-56)。This Elevated plus-maze is wooden, the labyrinth of the cross shape of the 60cm that is above the ground level, and is made up of four arm, wherein comprises two airtight arms (24cm) and two unlimited arms (1cm)。The center that every arm is all the region by 30cm × 5cm and 5cm × 5cm collectively constitutes。First mice is placed on the center in labyrinth, by its behavioral activity 5min of the camera record above labyrinth, then according to shooting record manual count mice time at unlimited arm and airtight arm and number of times, is only just recorded when mice extremity fully enter in arm。Time and number of times in arm entry will be used for statistical analysis time ratio and frequency ratio, wherein time ratio=open wide arm time/(open wide arm time+airtight arm time)；Frequency ratio=open wide arm number of times/(opening wide arm number of times+airtight arm number of times)。Every mouse experiment is all sent after terminating to return its rearging cage, and cleans maze device with 10% ethanol。Elevated plus-maze test mice enters the time opening wide arm and number of times can be used to evaluate the anxiety-like behavior of mice and medicine pharmacological activity antianxity, and experimental result shows,
Resveratrol does not affect the time and distance that mouse elevated plus-maze opens wide arm, airtight arm is treated, namely resveratrol does not cause the change of mouse anxiety sample behavior。
The impact that depression mouse elevated plus-maze is tested by table 1. resveratrol
(4) society's interference experiment
Mice is from its rearging cage, it is paired 10min in test-cage that transitioned into, unfamiliar, the mice of pairing should be same treatment group or normal saline group, the behavioral activity 10min of pairing mice is recorded continuously, then according to the attack time of shooting record manual count every mice and social interference time by the video camera above test-cage。Attack time is defined as attempting stinging, actual sting, box, the behavior such as play。Society is defined as another form of Body contact interference time, including smelling, lick or the contact of health。Do not carry out between mice contacting with each other and not being recorded。Invasion ratio be defined as invasion time/(invasion time+society interference time)。After experiment terminates, mice is sent in return rearging cage。
Experimental result shows: compared with matched group, and the attack time of depression mice society interference experiment, number of times dramatically increase, and interference time, number of times substantially reduce；Significantly reducing the social attack time of depression mice, number of times after giving resveratrol, add its society interference time, number of times, namely resveratrol has the behavior increasing depression mice social contact ability。
(5) forced swim test
The experimentation of forced swim test presses list of references content (PorsoltR.D., BertinA., JalfreM., etal (1978). " Behaviouraldespair " inratsandmice:straindifferencesandtheeffectsofimipramine .EurJPharmacol51 (3): 291-294.) carry out。It is high that mice is placed into the plastic cylinder 25cm(filling water) × 10cm(diameter) in, cylinder fills 23～25 DEG C, the water that 10cm is high, mice is forced in plastic cylinder 6min, when mice stops struggling in plastic cylinder, the state (only having small action to keep head to surface) keeping floating is considered as maintain static。Total testing time continues 6min, front 2min as the laundering period, and rear 4min records its swimming time by Enthovision8.5 auto Analysis and maintains static the time。Every mice has been swum, and is required for changing the water in cylinder。It is shown that compared with matched group, the set time of depression mouse forced swimming test dramatically increases, significantly reducing the set time of depression mice after giving resveratrol, namely resveratrol has reduction mice behavior depression。
(6) tail-suspention test
Being fixed by laboratory animal afterbody, head is downward, and animal struggles in this context, and this predicament is broken away from attempt, after still cannot breaking away from through great efforts, occurs that discontinuity is motionless, shows " behavioral despair " state。This behavioral despair model is similar with depression。After mouse tail, 1/3 place's adhesive tape is fixed, and head hangs on downwards on support, head distance table top 15cm, images, and shooting background is obvious contrast with mice hair color, and black mice adopts white background。Stop after timing 6min, with Enthovision8.5 software, the dead time of after mice four minutes (3-6min) is added up。Compared with matched group, the set time of depression Tail suspension test dramatically increases, and significantly reduces the set time of depression mice after giving resveratrol, and namely resveratrol has reduction mice behavior depression。
Embodiment 3: Mechanism Study
(1) cerebral tissue prepares
Mice 1h after administration passes through CO2Overdose of anesthesia is put to death, and takes its hippocampal tissue and cerebral tissue is placed in liquid nitrogen, be transferred in-80 DEG C of refrigerators。
Homogenate: cerebral tissue sample adds the 50mMKPO of 9 times of volumes4Buffer, the Triton-X-100 of 0.5%pH7.2 and 1 times are without in the protease inhibitor of EDTA, use Barnant homogenizer homogenate, brain homogenate thing is in 4 DEG C, 13,000g centrifugal 15min, take supernatant and are PGC-1 α, being stored in-80 DEG C of refrigerators, its protein concentration uses the detection of BCA protein assay kit。
(2) WesternBlotting experiment
PGC-1 α applied sample amount is 25 μ L/ holes, and loading is to 10% gel, and SDS-PAGE electrophoresis (100V, 1h), transferring film (350mA, constant current) 2h, 5%BSA close 1h；Rabbit anti-PGC-1 α polyclone primary antibodie (ab54481, Abcamcompany, 1:1000), 4 DEG C of overnight incubation, goat anti-rabbit igg two anti-(A0208, BeyotimeBiotechnology, 1:1000) hatches 1h；4 DEG C of overnight incubation of mouse-anti Beta-catenin primary antibodie (L002, EpitopeBiotechInc, 1:1000), mountain sheep anti-mouse igg two anti-(A0216, BeyotimeBiotechnology, 1:1000) hatches 1h。Expressing quantity uses Bio-RadQualityOne to analyze software and adds up。Pattern detection result corrects (having run same control sample in every piece of glue) by check sample, corrects finally by Beta-catenin, it is ensured that applied sample amount consistent。Result shows: compared with matched group, and the PGC-1 α expressing quantity of depression mice significantly reduces；The PGC-1 α protein expression level of depression mice is significantly increased after giving resveratrol。
(3) immunofluorescence
Taking hippocampal tissue and go to Fluorescent immunohistochemistry, being placed in mass fraction is in the mixed liquor that 3% glutaraldehyde/mass fraction is 4% paraformaldehyde/0.15moL/LPBS, and 4 DEG C preserve overnight。Within 2nd day, being sequentially placed into by the volume fraction of 0.15moL/LPBS solution preparation is 20%, 30% sucrose solution, is placed in Leica freezing microtome, and OCT embedding medium embeds, and makes coronal section with 12 μm。Add (pH6.0) microwave antigen retrieval 5min in 10mM citrate buffer, natural cooling。Volume fraction is that 5%BSA hatches 1h(37 DEG C), SIRT1 rabbit against murine polyclonal antibody (ab12193, Abcamcompany, 1:250), PGC-1 α rabbit against murine polyclonal antibody (ab54481, Abcamcompany, 1:250) overnight incubation (4 DEG C)。PBS rinses, and hatches lh by anti-rabbit IgG (P0183, BeyotimeBiotechnology, the 1:500) lucifuge of Cy3 labelling。PBS rinses, and redyes 5min with fluorescent dye (DAPI)。Rinse, mounting, shooting。
Immunofluorescence results shows: as it is shown in fig. 7, compared with matched group, the SIRT1 expressing quantity of depression mice significantly reduces；Significantly increasing the SIRT1 protein expression level of depression mice after giving resveratrol, namely resveratrol may be by raising the rise of SIRT1 protein expression, plays antidepressant effect。
Compared with matched group, as shown in Figure 8, the PGC-1 α expressing quantity of depression mice significantly reduces；Significantly increasing the PGC-1 α protein expression level of depression mice after giving resveratrol, namely resveratrol may be by raising the rise of PGC-1 protein expression, plays antidepressant effect。
(4) Hippocampal ultrastructure is observed
The hippocampus of mice that preserves in cryogenic refrigerator is taken out, with normal saline flushing, processes according to the following steps:
1. cut: tissue is accomplished 1mm3Size；
2. fix: fix more than 2h in advance with the glutaraldehyde (0.2M, PBS, pH7.4) of 3% at 4 DEG C, after the osmic acid of 1%, fix 2h；
3. dehydration: acetone is dehydration step by step；
4. embedding: 618 epoxy resin embeddings；
5. section: semithin section positions, LKB-5 type ultramicrotome is cut into slices, thickness 700nm；
6. dyeing: uranium acetate and lead citrate double staining；
7. microscopy: observe the change of Hippocampal ultrastructure under transmission electron microscope (TEM-1200EX/s), as shown in Figure 9。
Found that: resveratrol significantly reduces the damage of depression hippocampus of mice myelin, adds the integrity of myelin thousand tunic, protects the integrity of synapse。
Claims (8)
1. resveratrol application in preparing antidepressant drug。
2. the resveratrol according to claim 1 application in antidepressant sample medicine, it is characterised in that described resveratrol can increase hippocampal tissue SIRT1 and the expression of PGC-1 α albumen。
3. the resveratrol according to claim 2 application in antidepressant drug, it is characterised in that described resveratrol can increase the integrity of Hippocampus myelin membrane structure。
4. the application in preparing antidepressant drug of the resveratrol according to claim 1-3 any one, it is characterised in that described antidepressant sample behavior includes degradation under fatigue, anxiety, depression and social contact ability。
5. an antidepressant medicine, it is characterised in that described pharmaceutical pack is containing resveratrol。
6. medicine according to claim 5, it is characterised in that described medicine is made up of resveratrol and pharmaceutically acceptable carrier。
7. medicine according to claim 5, it is characterised in that described medicine is resveratrol is single active drug composition。
8. medicine according to claim 5, it is characterised in that described medicine is the compound recipe form that resveratrol forms with other ingredients with similar effect。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610049980.3A CN105687168A (en) | 2016-01-22 | 2016-01-22 | Application of resveratrol in preparation of antidepressant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610049980.3A CN105687168A (en) | 2016-01-22 | 2016-01-22 | Application of resveratrol in preparation of antidepressant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105687168A true CN105687168A (en) | 2016-06-22 |
Family
ID=56228529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610049980.3A Pending CN105687168A (en) | 2016-01-22 | 2016-01-22 | Application of resveratrol in preparation of antidepressant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105687168A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678880A (en) * | 2019-01-08 | 2019-04-26 | 江苏大学 | A kind of trifunctional benzoxazine monomer and preparation method thereof based on resveratrol |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721396A (en) * | 2009-11-09 | 2010-06-09 | 温州医学院 | Application of resveratrol in preparing medicament for treating tristimania |
| CN101801361A (en) * | 2007-06-22 | 2010-08-11 | e-生物有限公司 | Treatment of depression |
| CN102958516A (en) * | 2009-02-20 | 2013-03-06 | N.V.努特里西阿公司 | Use of resveratrol or another hydroxylated stilbene for preserving cognitive functioning |
| CN102973563A (en) * | 2011-09-07 | 2013-03-20 | 温州医学院 | Application of ombination of esveratrol and piperine used for preparation of medicament for treatment of depression |
| CN103386119A (en) * | 2012-05-08 | 2013-11-13 | 中国科学院上海生命科学研究院 | Application of SIRT1 in adjusting rhythm and improving rhythm disorder |
-
2016
- 2016-01-22 CN CN201610049980.3A patent/CN105687168A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101801361A (en) * | 2007-06-22 | 2010-08-11 | e-生物有限公司 | Treatment of depression |
| CN102958516A (en) * | 2009-02-20 | 2013-03-06 | N.V.努特里西阿公司 | Use of resveratrol or another hydroxylated stilbene for preserving cognitive functioning |
| CN101721396A (en) * | 2009-11-09 | 2010-06-09 | 温州医学院 | Application of resveratrol in preparing medicament for treating tristimania |
| CN102973563A (en) * | 2011-09-07 | 2013-03-20 | 温州医学院 | Application of ombination of esveratrol and piperine used for preparation of medicament for treatment of depression |
| CN103386119A (en) * | 2012-05-08 | 2013-11-13 | 中国科学院上海生命科学研究院 | Application of SIRT1 in adjusting rhythm and improving rhythm disorder |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109678880A (en) * | 2019-01-08 | 2019-04-26 | 江苏大学 | A kind of trifunctional benzoxazine monomer and preparation method thereof based on resveratrol |
| CN109678880B (en) * | 2019-01-08 | 2021-05-25 | 江苏大学 | Tri-functional benzoxazine monomer based on resveratrol and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Brazil et al. | Innate immune cell–epithelial crosstalk during wound repair | |
| Rohman et al. | Development of an experimental model of metabolic syndrome in sprague dawley rat | |
| Panduro et al. | Tissue tregs | |
| Morera et al. | Chronic heat stress up-regulates leptin and adiponectin secretion and expression and improves leptin, adiponectin and insulin sensitivity in mice | |
| Clément et al. | The lateral hypothalamic area controls paradoxical (REM) sleep by means of descending projections to brainstem GABAergic neurons | |
| Mizushima et al. | In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker | |
| Zhang et al. | Myricetin attenuated LPS induced cardiac injury in vivo and in vitro | |
| Altintas et al. | Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice | |
| Dropp | Mast cells in mammalian brain: I. Distribution | |
| Lemaitre et al. | The digestive tract of Drosophila melanogaster | |
| McNamee et al. | Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function | |
| Prendergast et al. | Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels | |
| McCall et al. | Effects of doxycycline on heartworm embryogenesis, transmission, circulating microfilaria, and adult worms in microfilaremic dogs | |
| Kazanci et al. | Analyses of changes on skin by aging | |
| Buchmann | Fish immune responses against endoparasitic nematodes–experimental models | |
| Ogawa et al. | Peripherally administered orexin improves survival of mice with endotoxin shock | |
| Chu et al. | Housefly maggots (Musca domestica) protein-enriched fraction/extracts (PE) inhibit lipopolysaccharide-induced atherosclerosis pro-inflammatory responses | |
| Yang et al. | Extension of Drosophila lifespan by Astragalus polysaccharide through a mechanism dependent on antioxidant and insulin/IGF-1 signaling | |
| Yin et al. | Effects of Cryptocaryon irritans infection on the survival, feeding, respiratory rate and ionic regulation of the marbled rockfish Sebastiscus marmoratus | |
| US11911425B2 (en) | Anti-aging composition comprising a plant extract | |
| Scharsack et al. | Excretory products of the cestode, Schistocephalus solidus, modulate in vitro responses of leukocytes from its specific host, the three-spined stickleback (Gasterosteus aculeatus) | |
| Peres et al. | Previous contact with Strongyloides venezuelensis contributed to prevent insulitis in MLD-STZ diabetes | |
| Xu et al. | Morphological characterization of postembryonic development of blood–spleen barrier in duck | |
| O'Brien et al. | A tale of three systems: toward a neuroimmunoendocrine model of obesity | |
| CN109576176A (en) | A kind of nanometer selenium bifidobacterium longum and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160622 |