CN117797137A - Application of morin in preparation of antidepressant drugs - Google Patents
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- CN117797137A CN117797137A CN202310455415.7A CN202310455415A CN117797137A CN 117797137 A CN117797137 A CN 117797137A CN 202310455415 A CN202310455415 A CN 202310455415A CN 117797137 A CN117797137 A CN 117797137A
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- morin
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- depression
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- YXOLAZRVSSWPPT-UHFFFAOYSA-N Morin Chemical compound OC1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 YXOLAZRVSSWPPT-UHFFFAOYSA-N 0.000 title claims abstract description 62
- UXOUKMQIEVGVLY-UHFFFAOYSA-N morin Natural products OC1=CC(O)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UXOUKMQIEVGVLY-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 235000007708 morin Nutrition 0.000 title claims abstract description 61
- 239000000935 antidepressant agent Substances 0.000 title claims abstract description 24
- 241000699670 Mus sp. Species 0.000 claims abstract description 43
- 239000003814 drug Substances 0.000 claims abstract description 17
- 230000001430 anti-depressive effect Effects 0.000 claims abstract description 15
- 229940005513 antidepressants Drugs 0.000 claims abstract description 14
- 241000699666 Mus <mouse, genus> Species 0.000 claims abstract description 10
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000007901 soft capsule Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 40
- 230000009182 swimming Effects 0.000 abstract description 16
- 238000002474 experimental method Methods 0.000 abstract description 15
- 239000000725 suspension Substances 0.000 abstract description 14
- 230000001684 chronic effect Effects 0.000 abstract description 9
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 abstract description 7
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 abstract description 7
- 239000006188 syrup Substances 0.000 abstract description 2
- 235000020357 syrup Nutrition 0.000 abstract description 2
- 230000003001 depressive effect Effects 0.000 abstract 1
- 230000000638 stimulation Effects 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000005720 sucrose Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 7
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 6
- 229960002464 fluoxetine Drugs 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 208000020401 Depressive disease Diseases 0.000 description 4
- 230000006978 adaptation Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000007267 depressive like behavior Effects 0.000 description 4
- 238000005286 illumination Methods 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 2
- 206010012374 Depressed mood Diseases 0.000 description 2
- 241000581650 Ivesia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000037326 chronic stress Effects 0.000 description 2
- 125000000881 corticosterone group Chemical group 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 238000011814 C57BL/6N mouse Methods 0.000 description 1
- 206010011971 Decreased interest Diseases 0.000 description 1
- 208000025967 Dissociative Identity disease Diseases 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 208000037490 Medically Unexplained Symptoms Diseases 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 241001229135 Nassa Species 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 206010040007 Sense of oppression Diseases 0.000 description 1
- 206010065604 Suicidal behaviour Diseases 0.000 description 1
- 206010042458 Suicidal ideation Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 208000025307 bipolar depression Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 229960002866 duloxetine Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960004341 escitalopram Drugs 0.000 description 1
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960004038 fluvoxamine Drugs 0.000 description 1
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960001785 mirtazapine Drugs 0.000 description 1
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 230000035771 neuroregeneration Effects 0.000 description 1
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000008674 spewing Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 201000006152 substance dependence Diseases 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000003867 tiredness Effects 0.000 description 1
- 208000016255 tiredness Diseases 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the technical field of medicine preparation, and particularly discloses application of morin in preparation of antidepressant medicines, wherein the influence of morin on behavior of a depressive mouse is researched by establishing a chronic Wen Heying induced depression model and a corticosterone induced depression model, and the improvement of morin on the behavior of the mouse like depression is found, which is manifested in that the preference rate of syrup is increased, and the immobility time of forced swimming and tail suspension experiments is shortened. The morin in the invention can obviously increase the preference rate of the sugar water of mice at the dosage of 40mg/kg and 80mg/kg, shortens the immobility time of forced swimming and tail suspension experiments, and has the potential for preparing antidepressant drugs.
Description
Technical Field
The invention relates to the technical field of medicine preparation, in particular to application of morin in preparing antidepressant medicines.
Background
Depression is now the most common psychological disorder, with continuous and long-term mood depression as the major clinical feature, the most important type of modern human mental disorder.
Clinically, the mood is low and the reality is too careless, the mood is low and subsides for a long time, from the beginning of smoldering to the last of sadness, spewing, pain, pessimistic and aversion, the feeling of living is hopefully afflicting itself every day, negatively, evading, and finally, the feeling of suicidal tendency and behavior is even more. The patient suffers from somatic symptoms. Chest oppression and shortness of breath. Only one person only wants to lie in the bed every day, and nothing wants to move. Has obvious anxiety feeling. More serious, the symptoms of schizophrenia such as auditory hallucination, paranoid disorder, multiple personality and the like can appear. Each episode of depression lasts for at least more than 2 weeks, one year, even years, most cases have a tendency to relapse.
The etiology of depression is not very clear, but it is believed that many factors in biological, psychological and social environments are involved in the pathogenesis of depression. Biological factors mainly relate to genetic, neurobiochemical, neuroendocrine, neuroregeneration and other aspects; the psychological predisposition closely related to depression is a pre-illness trait such as depressed qi. The adult stage encounters stressful life events, an important trigger condition that leads to the occurrence of clinically significant depressive episodes. However, these factors do not work alone, emphasizing the interaction between genetic and environmental or stress factors, and the point at which such interactions occur, has a significant impact in the occurrence of depression.
Diagnosis of depression should be based mainly on medical history, clinical symptoms, course of disease, physical examination and laboratory examination, and diagnosis of typical cases is generally not difficult. The internationally common diagnostic criteria are typically ICD-10 and DSM-IV. ICD-10 is mainly adopted in China, and refers to first-onset depression and recurrent depression, and bipolar depression is not included. Patients often have typical symptoms such as low mood, loss of interest and pleasure, poor vigor or tiredness. Other common symptoms are (1) reduced ability to focus on and pay attention; (2) the self-evaluation decreases; (3) self-criminal ideas and worthlessness (even in mild attacks); (4) consider the prospect to be dull and pessimistic; (5) ideas or behaviors of self-injury or suicide; (6) sleep disorders; (7) appetite decreases. The course of the disease lasts at least 2 weeks.
Treatment of depressive episodes achieves three goals: (1) the clinical cure rate is improved, the disability rate and the suicide rate are reduced to the maximum extent, and the key is that clinical symptoms are thoroughly eliminated; (2) improving the life quality and recovering the social function; (3) preventing recurrence. The treatment principle of depression mainly comprises: (1) individuation treatment; (2) the dosage is gradually increased, the minimum effective dose is adopted as far as possible, adverse reactions are minimized, and the medication compliance is improved; (3) sufficient pedicure treatment; (4) as single drug administration as possible, such as poor therapeutic effect, conversion therapy, synergistic therapy or combination therapy can be considered, but attention is paid to drug interactions; (5) pre-treatment informed notification; (6) closely observing the change of illness state and adverse reaction during treatment and timely treating; (7) can be combined with psychological treatment to increase curative effect; (8) actively treat other somatic diseases, substance dependence, anxiety disorder and the like which are co-morbid with depression.
Drug therapy is the primary treatment for depressive episodes above moderate. The current first-line antidepressants in clinic mainly include selective 5-hydroxytryptamine reuptake inhibitors (SSRI, representing the drugs fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and escitalopram), 5-hydroxytryptamine and norepinephrine reuptake inhibitors (SNRI, representing the drugs venlafaxine and duloxetine), norepinephrine and specific 5-hydroxytryptamine antidepressants (NaSSA, representing the drug mirtazapine), and the like. The traditional tricyclic antidepressants, tetracyclic antidepressants and monoamine oxidase inhibitors have the advantages of obviously reduced application due to larger adverse reaction.
At present, the medicine for treating the depression is single, and the treatment effect is not ideal, so that the searching of a novel component capable of being used for preparing the medicine for treating the depression is extremely important, and the method has great significance for preventing and treating the depression.
Disclosure of Invention
In order to solve the technical problems of single antidepressant drug and insignificant therapeutic effect, the invention provides the application of the morin in preparing the antidepressant drug, the morin in the invention can obviously increase the sugar water preference rate of mice at the dosage of 40mg/kg and 80mg/kg, shortens the immobility time of forced swimming and tail suspension experiments, and has the potential for preparing the antidepressant drug.
The invention provides an application of morin in preparing antidepressant drugs, wherein the morin has the following structural formula:
further, the morin is used for preparing an antidepressant for mice.
Further, the morin is used at a dosage of 20-80mg/kg according to the weight of the mice.
Further, the morin is used at a dosage of 40-80mg/kg according to the weight of the mice.
Further, the morin is used at a dosage of 40mg/kg according to the weight of the mice.
Further, the morin is used at a dosage of 80mg/kg according to the weight of the mice.
Further, the medicine is any pharmaceutically acceptable medicine formulation prepared by taking morin as an active ingredient and any pharmaceutically acceptable auxiliary material or medicine excipient.
Further, the dosage forms comprise granules, tablets, medicinal granules, soft capsules, dripping pills, ointments or injections.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the invention, by establishing a chronic mild stress depression model, researching the influence of morin on the depression-like behavior of a chronic stress induced mouse, the dose group (40 mg/kg) and the high-dose group (80 mg/kg) of morin are found to obviously increase the sugar water preference rate of experimental mice, and the immobility time of forced swimming and tail suspension experiments is shortened, so that the medium-dose morin and the high-dose morin have an antidepressant effect;
2. according to the invention, the mouse depression-like behavior is induced by corticosterone, and the morin is used for gastric lavage administration, so that the sugar water preference rate is obviously increased in a morin dosage group (40 mg/kg) and a morin high dosage group (80 mg/kg), and the immobility time of forced swimming and tail suspension experiments is shortened, thus the morin has an antidepressant effect.
Detailed Description
The following detailed description of specific embodiments of the invention is, but it should be understood that the invention is not limited to specific embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. The experimental methods described in the examples of the present invention are conventional methods unless otherwise specified, and materials, reagents, etc. used in the examples described below are commercially available.
Example 1: the application of morin in preparing antidepressant is provided.
1. Establishment of chronic Wen Heying depression model
1. Materials and methods
a. Preparation of laboratory animals
SPF grade C57BL/6N male mice 70, weight 18-22g, and adapted to feed for 7 days, during which time sufficient drinking water and feed are provided;
b. reagent/drug preparation
Morin, fluoxetine, 0.9% sodium chloride solution (normal saline), 1% (w/v) sucrose solution and pure water;
the morin has a chemical formula of C15H10O7, CAS No.:480-16-0, molecular weight: 302.24, the structural formula of the morin is:
2. model construction method
(1) Continuous 3 sugar preference baseline measurements were performed during the adaptive feeding period and the mice with abnormal sugar preference were removed (binge: total intake > 2 times the average total intake of mice; binge: total intake < 1/2 of average total intake of mice; sugar preference ratio < 60%), and after the end all remaining mice were randomized into normal and chronic stimulated groups, and consistent sugar preference ratio for each group was ensured;
(2) Normal feeding in the normal group without any stimulation; the chronic stimulation group was fed in single cages and received chronic mild stimulation;
stimulus factor: the chronic stimulation group performs water deprivation, pollution cage, inclined cage, strobing, noise, illumination for 2 times at night, intermittent illumination, empty bottle, restraint, day and night reversal and ice water swimming stimulation; the specific process is as follows:
a. water deprivation (24 h): water is forbidden and fasted for 24 hours;
b. dirty cage (24 h): 200mL of water is added into the cage to achieve a moist environment in the cage;
c. inclined cage (45 °): placing the cages in an inclined way by 45 degrees;
d. stroboscopic (150 flash/min): flashing stimulation in a dark environment;
e. noise (90±5 dB): continuously playing noise;
f. illuminating 2 times overnight: the lamp is not turned off at night, and the continuous 24h illumination is carried out;
g. intermittent illumination (interval 2 h): switching on and off the lamp once every interval of 2 hours;
h. empty bottle (1 h): after water and food withdrawal, an empty bottle is given;
i. binding (3 h): the mice are stuffed into a 50mL centrifuge tube for fixation;
j. day and night reversal: turning off the lamp in daytime and turning on the lamp at night;
k. ice water swimming (4 ℃,5 min): putting the mice into cold water with the temperature of 4 ℃ for swimming for 5min;
all the above a-k stimulation processes were performed independently and continuously, the stimulation sequence was randomly adjusted weekly, the stimulation was continued for 12 weeks, and the body weight of the mice was measured weekly.
2. Experimental grouping and administration
Sugar preference measurements were performed 8 weeks after continuous stimulation and stimulus tolerant mice were knocked out based on sugar preference ratio (sugar preference ratio was not significantly changed before and after stimulation). According to the principle that the sugar water preference ratio is consistent, the rest mice in the chronic stimulation group are randomly divided into a model group, a morin low-dose group (20 mg/kg), a morin medium-dose group (40 mg/kg), a morin high-dose group (80 mg/kg) and a positive control group (fluoxetine, 20 mg/kg), wherein 10 mice are in each group. All drugs were dissolved in 0.9% sodium chloride solution as a suspension, and administered by gavage at 10mL/kg, and the model and normal mice were given equal volumes of 0.9% sodium chloride solution by gavage for 4 weeks. Chronic mild stimulation was given simultaneously during the dosing period.
3. Behavioural assay method
1. Sugar water preference experiment (Sucrose preference test, SPT)
(1) And (5) sugar water adaptation.
Prior to the assay, all mice were fed in single cages, each cage was fitted with 1 bottle of 1% (w/v) sucrose solution and 1 bottle of pure water for 48 hours, during which sugar water and pure water bottle positions were exchanged every 12 hours, to avoid the mice developing conditional position preferences.
(2) Official SPT.
After the adaptation is finished, the mice are fasted and forbidden for 12 hours, then 1 bottle of weighed and marked new sucrose water and 1 bottle of pure water are respectively given, and after 12 hours, all the sugar water bottles and the pure water bottles are rapidly weighed and recorded, and according to the formula: sugar preference ratio (%) = [ sugar water intake/(sugar water intake+pure water intake) ]. Times.100%, the sugar preference ratio of mice was calculated.
(3) Forced swimming test (Forced swimming test FST)
The mice were placed in a cylindrical barrel with a height of 25cm and an inner diameter of 14cm, tap water with a height of 15cm and a temperature of 23.+ -. 2 ℃ was added and it was ensured that the tail of the mice could not touch the bottom of the barrel, the activity was recorded within 6min using a camera, and the immobility time of the mice within the following 4min was observed and recorded.
(4) Tail suspension experiment (Tail suspension test, TST)
The mouse tail is stuck on the cross rod and is reversely hung on the desktop, the camera is used for recording the activity condition within 6min, and the immobility time of the mouse within the last 4min is observed and recorded.
4. Experimental results
Table 1 effect of morin on chronic stress-induced mouse depression-like behavior (mean±sem, n=10)
Note that: # p <0.01 compared to the normal group; p <0.05, < p <0.01 compared to model group
Compared with the normal group, the sugar water preference rate of the mice in the model group is obviously reduced, and the immobility time of the forced swimming and tail suspension experiment is obviously prolonged, thus indicating that the model is successfully established. Compared with the model group, the morin medium-dose group (40 mg/kg) and the morin high-dose group (80 mg/kg) both obviously increase the preference rate of sugar water, shorten the immobility time of forced swimming and tail suspension experiments, and show that the morin medium-dose and the morin high-dose have antidepressant effect.
Example 2: the application of morin in preparing antidepressant is provided.
1. Establishment of corticosterone-induced depression model
1. Materials and methods
a. Preparation of laboratory animals
60 male ICR mice, 18-22g in weight;
b. reagent/drug preparation
Morin, fluoxetine, corticosterone, 0.9% sodium chloride solution (normal saline), 1% (w/v) sucrose solution, and pure water.
2. Experimental grouping and administration
Male ICR mice were randomized into 6 groups of 10 mice each (n=10), with 6 groups of mice each being normal, corticosterone, fluoxetine (20 mg/kg), morin low (20 mg/kg), morin medium (40 mg/kg), morin high (80 mg/kg). The administration mode of fluoxetine and morin is intragastric administration, and corticosterone (40 mg/kg) is subcutaneously injected 30min after administration, the administration volumes are 10mL/kg, and normal group is given an equal amount of physiological saline. After 21 days of continuous injection, behavioural experiments were performed.
3. Behavioural assay method
1. Sugar water preference experiment (Sucrose preference test, SPT)
(1) And (5) sugar water adaptation.
Prior to the assay, all mice were fed in single cages, each cage was fitted with 1 bottle of 1% (w/v) sucrose solution and 1 bottle of pure water for 48 hours, during which sugar water and pure water bottle positions were exchanged every 12 hours, to avoid the mice developing conditional position preferences.
(2) Official SPT.
After the adaptation is finished, the mice are fasted and forbidden for 12 hours, then 1 bottle of weighed and marked new sucrose water and 1 bottle of pure water are respectively given, and after 12 hours, all the sugar water bottles and the pure water bottles are rapidly weighed and recorded, and according to the formula: sugar preference ratio (%) = [ sugar water intake/(sugar water intake+pure water intake) ]. Times.100%, the sugar preference ratio of mice was calculated.
(3) Forced swimming test (Forced swimming test FST)
The mice were placed in a cylindrical barrel with a height of 25cm and an inner diameter of 14cm, tap water with a height of 15cm and a temperature of 23.+ -. 2 ℃ was added and it was ensured that the tail of the mice could not touch the bottom of the barrel, the activity was recorded within 6min using a camera, and the immobility time of the mice within the following 4min was observed and recorded.
(4) Tail suspension experiment (Tail suspension test, TST)
The mouse tail is stuck on the cross rod and is reversely hung on the desktop, the camera is used for recording the activity condition within 6min, and the immobility time of the mouse within the last 4min is observed and recorded.
4. Experimental results
Table 2 effect of morin on corticosterone-induced mouse depression-like behavior (mean±sem, n=10
Note that: compared to the normal group, #p <0.05, #p <0.01; p <0.05, < p <0.01 compared to model group
Compared with the normal group, the syrup preference rate of the corticosterone group mice is obviously reduced, and the immobility time of the forced swimming and tail suspension experiment is obviously prolonged, thus indicating that the establishment of the depression model is successful. Compared with the corticosterone group, the morin 40 and 80mg/kg groups obviously increase the preference rate of sugar water, shorten the immobility time of forced swimming and tail suspension experiments, and show that the morin has antidepressant effect.
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims (8)
1. The application of the morin in preparing the antidepressant is characterized in that the morin has the following structural formula:
2. the use of morin in the manufacture of an antidepressant according to claim 1, wherein the morin is used in the manufacture of an antidepressant in mice.
3. The use of morin according to claim 1 for the manufacture of an antidepressant, wherein said morin is administered in a dose of 20-80mg/kg according to the weight of the mouse.
4. The use of morin according to claim 3 for the preparation of antidepressant drugs, characterized in that said morin is used in a dose of 40-80mg/kg according to the weight of the mice.
5. The use of morin according to claim 4 for the manufacture of an antidepressant, wherein said morin is administered at a dose of 40mg/kg according to the weight of the mouse.
6. The use of morin according to claim 4 for the preparation of antidepressant drugs, wherein said morin is administered at a dose of 80mg/kg according to the weight of the mice.
7. The use of morin according to claim 1 for the preparation of antidepressant drugs, wherein the drugs are any pharmaceutically acceptable pharmaceutical dosage forms prepared from morin as an active ingredient and any pharmaceutically acceptable auxiliary material or pharmaceutical excipient.
8. The use of morin in the manufacture of an antidepressant according to claim 7, wherein said dosage form comprises a granule, a tablet, a granule, a soft capsule, a drop pill, an ointment or an injection.
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