CN103495112A - Application of melancholy-dispelling and liver-soothing capsule in preparation of antidepressant - Google Patents
Application of melancholy-dispelling and liver-soothing capsule in preparation of antidepressant Download PDFInfo
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- CN103495112A CN103495112A CN201310397937.2A CN201310397937A CN103495112A CN 103495112 A CN103495112 A CN 103495112A CN 201310397937 A CN201310397937 A CN 201310397937A CN 103495112 A CN103495112 A CN 103495112A
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Abstract
The invention discloses application of a melancholy-dispelling and liver-soothing capsule in preparation of an antidepressant. According to experimental studies, the melancholy-dispelling and liver-soothing capsule can substantially reduce dead time during tail suspension and forced swimming of behavioral despair model mice; according to open field experiments, dead time is substantially decreased, and spontaneous activities of the mice are not influenced. It is revealed that the melancholy-dispelling and liver-soothing capsule has a certain anti-depression effect. Meanwhile, the melancholy-dispelling and liver-soothing capsule can substantially antagonize decrease of body temperature of the mice caused by reserpine, which reveals that the capsule has the anti-depression effect which is realized through improvement of the level of a monoamine neurotransmitter in a synaptic cleft.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to the application of resolving depression liver relieving capsule in preparing antidepressants.
Background technology
Depression be take affective disorder as outstanding behaviours, not only affects patient's work, studying and living, hinders the performance of its social function, more likely causes suicide and jeopardizes patient's life.Along with the fierceness of social competition, the quickening of work rhythm, the patients with depression number also will present the trend [1] of rising.World Health Organization's latest survey statistic analysis result shows, the incidence rate of whole world depression is about 3.1%, and approaches 6% left and right in the incidence rate of developed country, in the adult population over 20 years old, patients with depression just increases with the speed in every year 113%, and oneself becomes frequently-occurring disease, commonly encountered diseases.
Depression is one group of different substantiality disease that the cause of disease is different with pathogenesis, and its symptom, sign are that the abnormal and acquired environment factor combined effect of congenital heredity factor, congenital neurodevelopment produces, and are difficult to explain by the single cause of disease and pathogenesis.The pathogeny of depression still imperfectly understands at present, antidepressant drug commonly used is mainly synthetic drug clinically, the drawbacks such as ubiquity drug resistance, side effect are large, therefore find safety, the study hotspot that efficient, the little especially natural antidepressant drug of antidepressant drug of side effect becomes this field.
Resolving depression liver relieving capsule is the accurate word Z20025813 of traditional Chinese medicines medicine, has JianPiRouGan, and the QI invigorating Detoxication, for the distending pain in the chest and hypochondrium due to stagnation of liver-QI with deficiency of the spleen, abdominal distention, chronic hepatitis.But act in antidepressants, have not been reported.
Summary of the invention
Goal of the invention: the object of the present invention is to provide the new application of resolving depression liver relieving capsule.
Technical scheme: the invention discloses the application of resolving depression liver relieving capsule in preparing antidepressants.
Above-mentioned resolving depression liver relieving capsule is mixed by the component of following percentage by weight: the Radix Curcumae of 1~5% Swertia mussotii Franch., 5~15% tangut dragonhead, 3~8% the Radix Astragali, 1~5% Radix Codonopsis, 3~8% Radix Pecteilis susannae, 5~15% Fructus Schisandrae Chinensis, 5~15% the Radix Paeoniae Alba, 1~5% Radix Angelicae Sinensis, Radix Ophiopogonis of 1~10%, 1~10 Radix Bupleuri, 1~10% Radix Scutellariae 1~10%, 1~10% Fructus Aurantii, 1~10% Poria, 2~6% Radix Glycyrrhizae and 1~3% starch.
Beneficial effect: can significantly reduce the outstanding tail of behavioral despair model mice and the dead time of forced swimming through experimental studies have found that the resolving depression Shugan Capsules, through opening open country, experiment showed, that remarkable minimizing, in the time of the dead time, does not affect the voluntary activity of mice.Prompting resolving depression Shugan Capsules has certain antidepressant effect; Meanwhile, the resolving depression Shugan Capsules mouse temperature that significantly the antagonism reserpine causes descends, and prompting resolving depression Shugan Capsules has certain antidepressant effect, and its antidepressant effect is realized by improving monoamine neurotransmitter level in synaptic space.
The specific embodiment
Embodiment 1:
The impact of resolving depression Shugan Capsules on behavioral despair model mice Depressive behavior
1 materials and methods
1.1 material
1.1.1 main medicine and reagent
The resolving depression liver extracting solution (provided by three general Pharmaceuticaies, extract voluntarily through this laboratory) that relaxes
Fluoxetine tablet (Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4,20120308);
Normal saline
1.1.2 laboratory animal
Clean level ICR mice, male, body weight (20 ± 2) g, Nantong University's Experimental Animal Center, the quality certification number: SCXK(Soviet Union) 2008-0010.The animal sub-cage rearing, keep the 12h circadian rhythm, and 22 ± 1 ℃ of room temperatures, freely drink water and ingest.
1.1.3 main experimental apparatus
Mice mining site performance testing instrument (self-control, diameter 30cm, high 20cm, bottom 19 deciles);
Mice forced swimming performance testing instrument (self-control, high 50cm, diameter 30cm, depth of water 30cm, 25 ± 1 ℃ of water temperatures);
Electronic balance (Sartorius, BS110S)
1.2 method
1.2.1 grouping and administration
Mice is divided into to five groups at random, 10 every group, is respectively blank group of (normal saline, 0.1ml/kg, i.g.), positive drug group (fluoxetine: 20mg/kg, i.g.), resolving depression Shugan Capsules low dosage (0.665g/kg, i.g.), middle dosage (1.33g/kg, i.g.), high dose (2.66g/kg, i.g.), detected after successive administration 7d.
1.2.2 spacious experiment
By mice as for the open case of mice.Observe 4min, respectively organize after mice horizontal score (wearing the lattice number of times), vertical score (the two forelimbs of mice are upwards praised number of times) in 2min, modify number of times (various motion of mice in each ministries and commissions' process of clean health, use, tongue and forelimb being made).
1.2.3 forced swimming experiment
Mice is placed in to the glass cylinder of 25 ℃ of depth of water 10cm, water temperature, observes 6min, respectively organize the accumulation dead time of mice in rear 4min.Dead time is judged: mice swims in the water surface, does not struggle, and only does some and must keep the action of head at the water surface.
1.2.4 outstanding tail experiment
The position of mice tail end 2cm is just pasted on a horizontal waddy, make mice become the reversal of the natural order of things state, the about 15cm of its head distance table top, by the sight line between dividing plate space between adjacent animal.Observe 6min, respectively organize the accumulation dead time of mice after record in 4min.Dead time criterion: during mice is draped, the location dead time during without any activity.
2 results
2.2 the resolving depression Shugan Capsules is on the impact of outstanding tail experiment dead time of desperate model mice
As shown in table 1, low, high (0.665g/kg, 2.66g/kg) dosage group of resolving depression Shugan Capsules continuous oral administration 7d can significantly shorten the dead time of outstanding tail experiment small mouse; Positive control drug fluoxetine (20mg/kg) can significantly shorten the dead time of mice equally in outstanding tail experiment.
Table 1 resolving depression soothing liver-QI on the impact of mouse tail suspension dead time (n=10,
)
Annotate: compare * p<0.05, * * p<0.01 with the blank group
2.3 the impact of resolving depression Shugan Capsules on the desperate model mice forced swimming experiment dead time
As shown in table 2, resolving depression Shugan Capsules middle and high (1.33g/kg, 2.66g/kg) dosage group successive administration 7d can significantly shorten the dead time of mice in the forced swimming experiment.
The impact of resolving depression Shugan Capsules on normal spontaneous activity in mice
Experimental result is in Table 3, give continuously mice 7d resolving depression Shugan Capsules basic, normal, high dosage (0.665g/kg, 1.330/kg, 2.66g/kg) group and fluoxetine (20mg/kg), in opening wild experiment, spontaneous activity in mice and matched group relatively do not have significant change, show that the resolving depression Shugan Capsules has no significant effect spontaneous activity in mice, and its antidepressant effect has specificity.
Table 2 resolving depression soothing liver-QI on the impact of mice forced swimming dead time (n=10,
)
Annotate: compare * p<0.05, * * p<0.01 with the blank group
Annotate: compare * p<0.05, * * p<0.01 with the blank group
3 conclusions
This experimentation proves, the middle and high dosage of resolving depression Shugan Capsules (1.33g/kg, 2.66g/kg) group continuous oral 7d can significantly shorten the dead time of mice in the forced swimming experiment, shows certain antidepressant effect; The resolving depression Shugan Capsules is low, high dose (0.667g/kg, 2.66g/kg) group continuous oral 7d can significantly shorten the dead time of mice in outstanding tail experiment, shows certain antidepressant effect.
Embodiment 2:
The impact of resolving depression Shugan Capsules on the behavior of drug-induced depression model mice
1 materials and methods
1.1 material
1.1.1 main medicine and reagent
Fluoxetine tablet (Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4,20120308);
Normal saline;
5-HTP: sweetening treatment company limited production in Hangzhou, lot number: CAC071205;
5-HTP (5-Hydroxy-DL-tryptophan, 5-HTP), Fluka company;
Apomorphine (ApomorphineHydrochlorideHemihydrate), Sigma company;
Reserpine: injection is Tianjin gold credit company limited product, lot number 1107171.
Noradrenaline bitartrate injection (NoradrenalineBitartrateInjection), Shanghai Hefeng Pharmaceutical Co., Ltd., lot number 110703.
1.1.2 laboratory animal
Clean level ICR mice, male, body weight (20 ± 2) g, Nantong University's Experimental Animal Center, the quality certification number: SCXK(Soviet Union) 2008-0010.The animal sub-cage rearing, keep the 12h circadian rhythm, and 22 ± 1 ℃ of room temperatures, freely drink water and ingest.
1.1.3 main experimental apparatus
Electronic balance (Sartorius, BS110S); Stopwatch; Electronic clinical thermometer (model MC-106B, Omron (China) Co., Ltd.)
1.2 method
1.2.15-HTP that induces gets rid of a behavioral experiment
Animal is divided into matched group, the basic, normal, high dosage of resolving depression Shugan Capsules (0.665g/kg, 1.33g/kg, 2.66g/kg), positive controls (FLU, 20mg/kg), 10 every group, totally 50, animal successive administration 7d.With reference to the method for Corne, each organizes mice last administration 90min pneumoretroperitoneum injection 5-HTP200mg/kg, after 10min, starts to observe, and records mice in 10min and gets rid of a number of times, respectively organizes the difference that mice gets rid of a number of times.
1.2.2 reserpine antagonistic experiment
Animal is divided into blank group, model group, the basic, normal, high dosage group of resolving depression Shugan Capsules (0.665g/kg, 1.330/kg, 2.66g/kg), positive controls (FLU, 20mg/kg), 10 every group, totally 60, animal successive administration 7d.The last administration is lumbar injection reserpine 5mg/kg simultaneously, after 4h, thermometer probe is inserted to animal anal 1.5-2cm place and measures the anus temperature, respectively organizes the difference of mice anus temperature.Matched group (Control) mice does not give reserpine.
1.2.3 high dose apomorphine antagonistic experiment
Animal is divided into blank group, model group, the basic, normal, high dosage group of resolving depression Shugan Capsules (0.665g/kg, 1.33/kg, 2.66g/kg), positive controls (FLU, 20mg/kg), 10 every group, totally 60, animal successive administration 7d.Mice last administration pre-test anus temperature, subcutaneous injection apomorphine (16mg/kg) after administration 90min, measure the anus temperature again after 30min, the difference that relatively before and after administration, mice anus temperature changes.Blank group (Control) mice does not give apomorphine.
1.2.4 mice norepinephrine toxicity Enhancement test
Animal is divided into blank group, the basic, normal, high dosage group of resolving depression Shugan Capsules (0.665g/kg, 1.330/kg, 2.66g/kg), positive controls (FLU, 20mg/kg), 12 every group, totally 60, animal successive administration 7d.After 7d mice administration 1h, the norepinephrine of subcutaneous injection 3mg/kg, then be placed in plastics cage by mice, the feed of freely intaking, the mortality rate of each administration group and blank group small mouse relatively after 48h.
2 experimental results
2.1 the impact of getting rid of a behavior that the resolving depression Shugan Capsules is induced 5-HTP
Experimental result, in Table 4, is compared with blank group, the basic, normal, high dosage group of positive drug fluoxetine group and resolving depression Shugan Capsules (0.665g/kg, 1.33g/kg, 2.66g/kg), there are no significant difference.
Table 4 resolving depression Shugan Capsules on the 5-HTP inducing mouse get rid of the head impact (n=10,
)
Annotate: compare * p<0.05, * * p<0.01 with the blank group
2.2 the impact of resolving depression Shugan Capsules on the reserpine antagonistic experiment
Experimental result, in Table 5, is compared with the blank group, and the mouse temperature that reserpine is processed obviously descends; The basic, normal, high dosage group of resolving depression Shugan Capsules (0.665g/kg, 1.33g/kg, 2.66g/kg), the successive administration 7d mouse temperature that significantly the antagonism reserpine causes descends, the antidepressant effect of prompting resolving depression Shugan Capsules with affect maincenter monoaminergic nerve system.
Table 5 resolving depression Shugan Capsules on the impact of reserpine antagonistic experiment (n=10,
)
Annotate: compare #P<0.05, ##P<0.01 with the blank group; Compare * P<0.05, * * P<0.01 with model group
2.3 the impact of resolving depression Shugan Capsules on high dose apomorphine antagonistic experiment
Experimental result, in Table 6, is compared with the blank group, and the mouse temperature that apomorphine is processed obviously descends; Compare the temperature decline that positive drug fluoxetine group has remarkable antagonism apomorphine to cause, and comparing with model group, the basic, normal, high dosage group of resolving depression Shugan Capsules (0.665g/kg, 1.33g/kg, 2.66g/kg) there are no significant difference with model group.
Table 6 resolving depression Shugan Capsules on the impact of high dose apomorphine antagonistic experiment (n=10,
)
Annotate: compare #P<0.05, ##P<0.01 with the blank group; Compare * P<0.05, * * P<0.01 with model group
2.4 the impact of resolving depression Shugan Capsules on norepinephrine toxicity Enhancement test
Experimental result, in Table 7, is compared with blank group, and positive drug fluoxetine group has significant difference, and the basic, normal, high dosage group of resolving depression Shugan Capsules (0.665g/kg, 1.33g/kg, 2.66g/kg) there are no significant difference.
Table 7 resolving depression Shugan Capsules on the impact of norepinephrine toxicity Enhancement test (n=12,
)
Annotate: compare * p<0.05, * * p<0.01 with the blank group
3 conclusions
This experimentation proves, basic, normal, high dosage (the 0.665g/kg of resolving depression Shugan Capsules, 1.33g/kg, 2.66g/kg) the group successive administration 7d mouse temperature decline that significantly the antagonism reserpine causes, prompting resolving depression Shugan Capsules has antidepressant effect, and its antidepressant effect is with to affect maincenter monoaminergic nerve system relevant.
Claims (2)
1. the application of resolving depression liver relieving capsule in preparing antidepressants.
2. resolving depression liver relieving capsule according to claim 1, it is characterized in that, mixed by the component of following percentage by weight: the Radix Curcumae of 1~5% Swertia mussotii Franch., 5~15% tangut dragonhead, 3~8% the Radix Astragali, 1~5% Radix Codonopsis, 3~8% Radix Pecteilis susannae, 5~15% Fructus Schisandrae Chinensis, 5~15% the Radix Paeoniae Alba, 1~5% Radix Angelicae Sinensis, Radix Ophiopogonis of 1~10%, 1~10 Radix Bupleuri, 1~10% Radix Scutellariae 1~10%, 1~10% Fructus Aurantii, 1~10% Poria, 2~6% Radix Glycyrrhizae and 1~3% starch.
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CN115252749A (en) * | 2022-03-26 | 2022-11-01 | 吉林大学 | Application of aconite root preparation for regulating middle warmer as antidepressant targeting medicine |
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Non-Patent Citations (2)
Title |
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国家药品监督管理局: "《国家药品监督管理局国家中成药标准汇编中成药地方标准上升国家标准部分内科肝胆分册》", 31 December 2002 * |
张海: "试述柔肝健脾法在抑郁症中的运用", 《中医药学报》 * |
Cited By (1)
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CN115252749A (en) * | 2022-03-26 | 2022-11-01 | 吉林大学 | Application of aconite root preparation for regulating middle warmer as antidepressant targeting medicine |
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Application publication date: 20140108 |