CN101485674A - Application of naringin in preparing anti-depression medicament - Google Patents
Application of naringin in preparing anti-depression medicament Download PDFInfo
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Abstract
The invention discloses application of naringin in preparation of an anti-depression medicine. Dosage forms of the medicine are pharmaceutically acceptable dosage forms such as a tablet, a capsule, a solution, a suspension, an injection, a dripping injection and the like. A composition consists of the naringin as well as aglycon and secondary glucoside which are pharmaceutically acceptable and are generated through hydrolysis or enzymolysis, and is combined with pharmaceutical carriers to prepare various pharmaceutical dosage forms. The medicine has small toxicity, and overcomes the disadvantages of the prior anti-depression medicines such as excitation, constipation, anuresis, dizziness, hypersomnia, tremor and the like.
Description
Technical field:
The present invention relates to medical technical field, exactly it is the application of naringin in the preparation antidepressant drug.
Background technology:
Naringin (Naringin) is the flavanone glycosides compound, for Rutaceae citrus plant secondary metabolite, is distributed widely in a lot of plants.Studies show that naringin has stronger biological activity at aspects such as blood fat reducing, calmness, antioxidation, antitumor, antifungal, atherosclerosiss.China Patent No.: 03113605.2 discloses the patent of invention that name is called " it is anxious that naringin is used for the preparation treatment; the medicine of chronic bronchitis ", the patent No.: 03126908.7 discloses the patent of invention that name is called " application of naringin in the supportive treatment severe acute respiratory syndrome medicine of preparation ", the patent No.: 200510101404.0 disclose the patent of invention that name is called " naringin is prevented and treated application in the influenza medicine in preparation ", the patent No.: 200810300599.5 disclose the patent of invention that name is called " application of naringin in the preparation oral cavity nursing health products ", and it is anxious in the preparation treatment to disclose naringin, chronic bronchitis, supportive treatment severe acute respiratory syndrome, prevent and treat the application in influenza medicine and the oral cavity nursing health products.Do not see the new purposes of naringin in preparation anti-depression aspect medicine.
The naringin structural formula:
Summary of the invention:
The invention provides the antidepressant new purposes of naringin.Naringin and pharmaceutically acceptable aglycon that generates through hydrolysis or enzymolysis and secondary glycosides etc. are used for prevention or treatment anxiety state or depressive state.
Contain naringin and pharmaceutically acceptable aglycon that generates through hydrolysis or enzymolysis and secondary glycosides etc. or with it as the Pharmaceutical composition that active component is formed, comprise and the pharmaceutical carrier combination, be used for prevention or treatment depressive state.Wherein said sick body is a mammal.Naringin and pharmaceutically acceptable aglycon that generates through hydrolysis or enzymolysis and secondary glycosides etc., or can be by oral, non-intestinal or topical routes with its Pharmaceutical composition of forming as active component, form of administration can be pharmaceutically acceptable dosage forms such as tablet, capsule, solution, suspension, injection, drip liquid, lyophilized powder.
Advantage of the present invention is: the present invention has disclosed naringin and has had antidepressant effect, for its application provides new approach.And toxicity is little, does not have the excited uneasiness, constipation, urine retention of conventional antidepressants, dizzy, drowsiness, shortcoming such as tremble.
The specific embodiment:
Below zoopery be to further describe to of the present invention, but and do not mean that any limitation of the invention.The experiment of example 1. autonomic activities irritabilitys
1. laboratory animal
The Wistar rat, male, body weight 200～220g, the SPF grade standard is weighed animal, and numbering is selected totally 30 of healthy rats.By the ordering of body weight size, be divided into 3 groups with randomized blocks, 10 every group.If blank group, positive controls and naringin drug sample group.
2. sample source and processing
(1) blank group: normal saline, NaCl content 0.9%.
(2) positive controls: get fluoxetine Hydrochloride and use the normal saline standardize solution in volumetric flask, fluoxetine Hydrochloride concentration is 1.8mg/ml.Dosage is 7.2mg/kg.
(3) naringin sample sets: it is an amount of to get naringin, and in volumetric flask, naringin concentration is 1.6mg/ml with the normal saline standardize solution.Used naringin sample purity is more than 95%, and dosage is 8mg/kg.
3. experimental technique (prologue experiment)
Adopting the bottom surface is foursquare spacious case, long 100cm, and wide 100cm, high 50cm, the bottom surface is divided into close fan-shaped of 100 areas with black line.During experiment rat is placed on the spacious positive center of case, gets over lattice number (at least 3 pawls stride across the border) with horizontal movement in the rat 5min and estimate its mobility; Estimate its inquiry with the upright number of times that moves both vertically (two fore paw built on stilts).Whether have autonomous excitation, simultaneously with the contrast of accompanying of the blank group that gives normal saline and the positive controls that gives the positive control drug fluoxetine Hydrochloride by autonomic movement situation of change before and after the naringin administration group administration relatively if investigating naringin.
3. experimentation
By observing the activity of rat in spacious case, horizontal movement is got over the lattice number and the axial number of times that moves both vertically in the record 5min before the administration; After 7 days, observe the activity of rat in spacious case in administration, horizontal movement is got over the lattice number and the axial number of times that moves both vertically in the record 5min.Each group experimental data is handled with the SPSS statistical software, and the horizontal movement rate of change and the rate of change computational methods that move both vertically are as follows:
Lattice number * 100% is got in horizontal movement before horizontal movement rate of change=(administration after 7 days horizontal movement horizontal movement lattice number more before lattice number-administration) more/administration
Lattice number * 100% more that moves both vertically before rate of change=(administration move both vertically after 7 days the lattice number more that moves both vertically before lattice number-administration more)/administration moves both vertically
Each group experimental data is carried out the t check, investigate it and whether have significant difference.
4. experimental result
By statistics, each sample sets autonomic movement situation sees Table 1.
Before table 1. administration with administration each sample sets prologue experiment autonomic movement situation of change after 7 days
Utilization SPSS software, carry out the t check, autonomic movement situation before and after relatively more blank respectively group, naringin group and the administration of fluoxetine Hydrochloride group, the same with the blank group with positive control drug fluoxetine Hydrochloride group, the horizontal movement of naringin group and the difference that moves both vertically that there are no significant before and after the administration (P〉0.05), showing after giving naringin does not have autonomous excitation to the central nervous system.
The experiment of example 2. chronic stress rats prologue
1. laboratory animal
The Wistar rat, male, body weight 200～220g, the SPF grade standard is weighed animal, and numbering is selected totally 40 of healthy rats.By the ordering of body weight size, be divided into 5 groups with randomized blocks, 10 every group.If blank group, pathological model group, positive controls and naringin drug sample group.
2. sample source and processing
(1) blank group: normal saline, NaCl content 0.9%.
(2) pathological model group: normal saline, NaCl content 0.9%.
(3) positive controls: get fluoxetine Hydrochloride and use the normal saline standardize solution in volumetric flask, fluoxetine Hydrochloride concentration is 1.8mg/ml, and dosage is 7.2mg/kg.
(4) naringin sample sets: it is an amount of to get naringin, and in volumetric flask, naringin concentration is 1.6mg/ml with the normal saline standardize solution.Used naringin sample purity is more than 95%, and dosage is 8mg/kg.
3. experimental technique
(1) preparation of rat chronic Stress model: chronic stress stimulates as a kind of non-damage, with the process of human psychosoma disease similarity is arranged, the simulation that chronic stress model reality is tested " stress state " that run in people's daily life, for the specific clinical antidepressants of screening the good suitability is arranged, this experiment is just based on the chronic stress model, give naringin and positive control drug, investigate the antidepressant effect of naringin.
In the preparation of rat chronic Stress model, make stress stimulation meet the characteristics of unpredictability as far as possible, 28d is by the intensity of every day 1 or 2 kind of stimulation continuously, give alternately that rat is following to be stimulated: fasting 24h, prohibit water 24h, restriction and ingest that 2h, pairing raise 12h, the 45 ° of 2h of cage that incline, the 12h that throws light on all night, moist (200ml water is added to the 100g bedding and padding) 12h, stroboscopic (100min/s) 1h, white noise (110dB) 1h, forced swimming (4 ℃ of water temperatures) 5min, the braking 1h of raising, preparation chronic stress model.It is as follows that each sample sets stress reach the administration situation:
A. blank group: do not stimulate, give normal saline.
B. pathological model group: stimulate to give normal saline simultaneously.
C. positive controls: stimulate to give fluoxetine Hydrochloride simultaneously with the formulated medicinal liquid of physiological saline solution.
D. naringin sample sets: stimulate to give naringin simultaneously with the formulated medicinal liquid of physiological saline solution.
(2) prologue experiment: adopting the bottom surface is foursquare spacious case, long 100cm, and wide 100cm, high 50cm, the bottom surface is divided into close fan-shaped of 100 areas with black line.During experiment rat is placed on the spacious positive center of case, gets over lattice number (at least 3 pawls stride across the border) with horizontal movement in the rat 5min and estimate its mobility; Estimate its inquiry with the upright number of times that moves both vertically (two fore paw built on stilts).Investigate naringin by naringin administration group before and after the administration relatively with pathological model group autonomic movement rate of change (comprising the horizontal movement rate of change and the rate of change that moves both vertically) and whether have antidepressant effect, the while is with the contrast of accompanying of the blank group that gives normal saline and the positive controls that gives the positive control drug fluoxetine Hydrochloride.
4. experimentation
By observing the activity of rat in spacious case, horizontal movement is got over the lattice number and the axial number of times that moves both vertically in the record 5min before the administration; After 28 days, observe the activity of rat in spacious case at chronic stress, horizontal movement is got over the lattice number and the axial number of times that moves both vertically in the record 5min.The horizontal movement rate of change and the rate of change computational methods that move both vertically are as follows:
The horizontal movement rate of change=(stress be after 28 days horizontal movement more the lattice number-stress before horizontal movement lattice number more)/stress before horizontal movement get over lattice number * 100%
Move both vertically rate of change=(the lattice number that stress move both vertically after 28 days more-stress before the lattice number more that moves both vertically)/stress before lattice number * 100% more that moves both vertically
The result obtains positive number for increasing, and negative is handled each group experimental data for descending with the SPSS statistical software, carry out the t check, investigates naringin group and pathological model group autonomic movement situation and whether has significant difference.
5. experimental result
By statistics, each sample sets autonomic movement situation sees Table 2.
Each sample sets prologue experiment autonomic movement situation of change of table 2 chronic stress rat model
Utilization SPSS software, carry out the t check, relatively there is extremely significant difference (P＜0.01) in the pathological model group with blank group autonomic movement situation (the horizontal movement rate of change and the rate of change that moves both vertically) before and after administration, show under the state of chronic stress, rat do not have under the pharmaceutical intervention its autonomic movement emotionally condition be subjected to influence, the horizontal movement rate of change and the rate of change that moves both vertically all obviously descend, and prompting chronic stress model prepares successfully; Naringin group, positive control drug group and pathological model group autonomic movement situation before and after administration compares (the horizontal movement rate of change and the rate of change that moves both vertically) and all has extremely significant difference (P＜0.01), show that naringin and positive control drug fluoxetine Hydrochloride all can be to having significant resistant function because the rat horizontal movement rate of change that chronic stress causes and the rate of change that moves both vertically descend, the prompting naringin has opposing because the pharmacologically active that the depressed autonomic activities that causes reduces.
Example 3. chronic stress rat body weight increment rate determination experiments
1. laboratory animal
The Wistar rat, male, body weight 200～220g, the SPF grade standard is weighed animal, and numbering is selected totally 40 of healthy rats.By the ordering of body weight size, be divided into 5 groups with randomized blocks, 10 every group.If blank group, pathological model group, positive controls and naringin drug sample group.
2. sample source and processing
(1) blank group: normal saline, NaCl content 0.9%.
(2) pathological model group: normal saline, NaCl content 0.9%.
(3) positive controls: get fluoxetine Hydrochloride and use the normal saline standardize solution in volumetric flask, fluoxetine Hydrochloride concentration is 1.8mg/ml, and dosage is 7.2mg/kg.
(4) naringin sample sets: it is an amount of to get naringin, and in volumetric flask, naringin concentration is 1.6mg/ml with the normal saline standardize solution.Used naringin sample purity is more than 95%, and dosage is 8mg/kg.
3. experimental technique
(1) preparation of rat chronic Stress model: the preparation of rat chronic Stress model and each sample sets stress reach the administration situation all with example 2.
(2) weight increase rate experiment: rat is after being stimulated by chronic stress, will the performance of loss of appetite appears, the minimizing of feed will cause the decline of weight increase speed, therefore, by relatively naringin group and pathological model group can be investigated the naringin antagonism owing to the impaired weight increase speed that causes of digestive system function that the rat chronic stress stimulation causes descends in the situation of change of administration front and back body weight increment rate; Investigate the difference of naringin group and pathological model group administration front and back respectively organizing the rat body weight increment rate and whether have significance, the positive controls that gives the blank group of normal saline simultaneously and give the positive control drug fluoxetine Hydrochloride contrast of accompanying.
4. experimentation
Rat body weight is respectively organized in weighing respectively before administration, and chronic stress stimulated after 28 days, and rat body weight is respectively organized in weighing once more, investigates naringin group and the administration of pathological model group front and back and respectively organizes the rat body weight increment rate.The computational methods of rat body weight increment rate are as follows:
The weight increase rate=(stress be after 28 days rat body weight-stress before rat body weight)/stress before rat body weight * 100%
Each group experimental data is handled with the SPSS statistical software, carried out the t check, investigate naringin group and pathological model group rat body weight increment rate and whether have significant difference.
5. experimental result
By statistics, each sample sets rat body weight increment rate situation sees Table 3.
Each sample sets rat body weight increment rate situation of change of table 3 chronic stress rat model
Utilization SPSS software, carry out the t check, relatively there is extremely significant difference (P＜0.01) in the pathological model group with blank group body weight increment rate before and after administration, show under the state of chronic stress, its digestive system function has been subjected to influence to rat under the pharmaceutical intervention not having, weight increase speed is starkly lower than blank group, points out the chronic stress model to prepare successfully simultaneously; More all there is extremely significant difference (P＜0.01) in naringin group, positive control drug group and pathological model group body weight increment rate before and after administration, show that naringin and positive control drug fluoxetine Hydrochloride all can be to having significant resistant function because the rat body weight that chronic stress causes advances the speed to descend, the prompting naringin has opposing because the depressed not normal pharmacologically active of digestive system function that causes.
Example 4. chronic stress rat sucrose are degree of having a liking for determination experiment partially
1. laboratory animal
The Wistar rat, male, body weight 200～220g, the SPF grade standard is weighed animal, and numbering is selected totally 40 of healthy rats.By the ordering of body weight size, be divided into 5 groups with randomized blocks, 10 every group.If blank group, pathological model group, positive controls and naringin drug sample group.
2. sample source and processing
(1) blank group: normal saline, NaCl content 0.9%.
(2) pathological model group: normal saline, NaCl content 0.9%.
(3) positive controls: get fluoxetine Hydrochloride and use the normal saline standardize solution in volumetric flask, fluoxetine Hydrochloride concentration is 1.8mg/ml, and dosage is 7.2mg/kg.
(4) naringin sample sets: it is an amount of to get naringin, and in volumetric flask, naringin concentration is 1.6mg/ml with the normal saline standardize solution.Used naringin sample purity is more than 95%, and dosage is 8mg/kg.
3. experimental technique
(1) preparation of rat chronic Stress model: the preparation of rat chronic Stress model and each sample sets stress reach the administration situation all with example 2.
(2) sucrose water degree of having a liking for experiment partially: rat is after being stimulated by chronic stress, will the performance that interest goes down appears, this experiment is at first carried out sucrose water to rat and is had a liking for training partially before carrying out chronic stress, set up its preference to sucrose solution, after carrying out the chronic stress stimulation, can cause the decline of degree of having a liking for partially of sucrose water for the rat of antidepressant drug because of the disappearance of interest, therefore, by naringin group relatively and pathological model group sucrose water degree of having a liking for situation of change partially before and after administration, can investigate the anhedonia that the naringin antagonism causes owing to the rat chronic stress stimulation; Investigate and respectively to organize rat sucrose water before and after naringin group and the administration of pathological model group and whether have significance partially between degree of the having a liking for rate of change, the while is with the contrast of accompanying of the blank group that gives normal saline and the positive controls that gives the positive control drug fluoxetine Hydrochloride.
4. experimentation
Earlier rat is carried out learning training before administration: water is prohibited in fasting, only gives 1% sucrose water 48h; Sucrose degree of having a liking for is partially measured: training finishes the normal drinking water in back and raises 3d, and water 23h is prohibited in fasting again, allows rat freely drink 2 bottles of different water then, and wherein one bottle is 1% sucrose water, and one bottle is tap water.Carry out the amount of drinking water (g) of 1h and measure, by formula calculate sucrose degree of having a liking for partially.Rat conform 1 week back by sucrose partially degree of having a liking for 40 rat equilibriums are divided into 4 groups: chronic stress is measured rat sucrose water degree of having a liking for partially after stimulating 28 days once more.Calculate sucrose degree of having a liking for rate of change partially simultaneously
Sucrose is degree of having a liking for=sucrose diseases caused by retention of fluid consumption/(sucrose diseases caused by retention of fluid consumption+tap water amount of drinking) * 100% partially
Sucrose partially degree of having a liking for rate of change=(stress be after 28 days sucrose partially degree of having a liking for-stress before sucrose degree of having a liking for partially)/stress before sucrose degree of having a liking for * 100% partially
Each group experimental data is handled with the SPSS statistical software, carried out the t check, whether investigation naringin group and pathological model group rat sucrose degree of having a liking for rate of change partially exist significant difference.
5. experimental result
By statistics, each sample sets rat sucrose partially degree of having a liking for rate of change situation see Table 4.
Utilization SPSS software, carry out the t check, pathological model group and blank group before and after administration sucrose partially degree of having a liking for rate of change relatively have extremely significant difference (P＜0.01), show under the state of chronic stress, rat is not having to have caused its disappearance to the interest of original foundation under the pharmaceutical intervention, sucrose degree of having a liking for rate of change partially is starkly lower than blank group, points out the chronic stress model to prepare successfully simultaneously; Naringin group, positive control drug group and pathological model group before and after the administration sucrose partially degree of having a liking for rate of change more all has difference (P＜0.01) extremely significantly, show that naringin and positive control drug fluoxetine Hydrochloride all can have significant resistant function to the rat body weight anhedonia symptom that causes owing to chronic stress, the prompting naringin has opposing because the depressed pharmacologically active that causes the brain malfunction relevant with anhedonia.
Each sample sets rat sucrose of table 4. chronic stress rat model is degree of having a liking for rate of change partially
Example 5. chronic stress rat urine quantitative change determination experiments
1. laboratory animal
The Wistar rat, male, body weight 200-220g, the SPF grade standard is weighed animal, and numbering is selected totally 40 of healthy rats.By the ordering of body weight size, be divided into 5 groups with randomized blocks, 10 every group.If blank group, pathological model group, positive controls and naringin drug sample group.
2. sample source and processing
(1) blank group: normal saline, NaCl content 0.9%.
(2) pathological model group: cattle reason saline, NaCl content 0.9%.
(3) positive controls: get fluoxetine Hydrochloride and use the normal saline standardize solution in volumetric flask, fluoxetine Hydrochloride concentration is 1.8mg/ml, and dosage is 7.2mg/kg.
(4) naringin sample sets: it is an amount of to get naringin, and in volumetric flask, naringin concentration is 1.6mg/ml with the normal saline standardize solution.Used naringin sample purity is more than 95%, and dosage is 8mg/kg.
3. experimental technique
(1) preparation of rat chronic Stress model: the preparation of rat chronic Stress model and each sample sets stress reach the administration situation all with example 2.
(2) voided volume changes determination experiment: studies show that hypothalmus-pituitary-adrenal axis (hpa axis) participates in the pathogenesis of depression, hypothalamus is the high-level center of endocrine regulation hormone.Hypothalamus has the function of secreting hormone, the MgC cell of chamber coker is mainly secreted vassopressin, it acts on kidney, the heavily absorption that moisturizes, reduce the discharge of moisture, therefore, this experiment by observe stress before and after the variation of rat urine amount can reflect the hyperfunction degree of hpa axis to a certain extent, by naringin group relatively and the pathological model group quantitative change rate of before and after administration, urinating, can investigate the naringin antagonism because the effect of the hyperfunction voided volume minimizing that causes of the hpa axis that the rat chronic stress stimulation causes; Respectively organize between the rat urine amount rate of change whether have significance before and after investigating naringin group and the administration of pathological model group, the while is with the contrast of accompanying of the blank group that gives normal saline and the positive controls that gives the positive control drug fluoxetine Hydrochloride.
4. experimentation
Collect respectively before administration and respectively organize the urine that rat 12h is produced, chronic stress stimulated after 28 days, collected once more and respectively organized the urine that rat 12h is produced, and investigated naringin group and the administration of pathological model group front and back and respectively organized rat urine amount rate of change.In every 100g rat body weight, computational methods are as follows during calculating:
The voided volume rate of change=(stress be after 28 days every 100g rat body weight 12h voided volume-stress before every 100g rat body weight 12h voided volume)/stress before every 100g rat body weight 12h voided volume * 100%
The result obtains positive number for increasing, and negative is handled each group experimental data for descending with the SPSS statistical software, carry out the t check, investigates naringin group and pathological model group rat urine amount rate of change and whether has significant difference.
5. experimental result
By statistics, each sample sets rat urine amount rate of change situation sees Table 5.
Each sample sets rat urine amount rate of change of table 5 chronic stress rat model
Utilization SPSS software, carry out the t check, relatively there is extremely significant difference (P＜0.01) in the pathological model group with the blank quantitative change rate of urinating of organizing before and after administration, show under the state of chronic stress, rat is not having to have caused it owing to the hpa axis hyperfunctioning produces the symptom that voided volume reduces under the pharmaceutical intervention, the voided volume rate of change is starkly lower than blank group, points out the chronic stress model to prepare successfully simultaneously; More all there is significant difference (P＜0.05) in naringin group, positive control drug group and the pathological model group quantitative change rate of urinating before and after the administration, show that naringin and positive control drug fluoxetine Hydrochloride all can have significant resistant function to the symptom that produces the voided volume minimizing owing to the hpa axis hyperfunctioning, the prompting naringin has opposing because depression causes hpa axis pharmacologically active hyperactivity.
Example 6. monoamine oxidase A suppress active testing
1. sample and reagent
Naringin: purchase in Chinese biological goods calibrating institute, content 98%
Pargyline: sigma company product, specification 1g/ bottle
Sodium phosphate, sucrose are all purchased in Beijing chemical reagents corporation
MAO active testing test kit: purchase in Nanjing and build up bio-engineering research institute, test kit is formed:
Reagent one: aniline solution (0.016mol/L)
Reagent two: pH7.6 Tris buffer
Reagent is crossed solution chlorate's (reaction terminating liquid) at three: 10%
Reagent four: cyclohexane extraction reagent
2. experimental technique
Monoamine neurotransmitter is the medium of nervous system conducted signal, its normal presence is the prerequisite that nervous system normally plays a role, in the pathogenesis research of depression, researcher finds that the minimizing of monoamine neurotransmitter and the morbidity of depression have dependency, and the activity of monoamine oxidase A (MAO-A) increases the monoamine neurotransmitter minimizing that directly causes synaptic space unusually, some antidepressants of clinical practice just are based on monoamine hypothesis design (as imipramine, phenelzine etc.), therefore, seeking oxidase inhibitor is to find to have one of approach of antidepressant activity medicine.
The oxidation under the MAO effect of this experimental basis benzylamine generates the principle of benzyl aldehyde, with the amount of cyclohexane extraction extract product at 242nm wavelength place trap mensuration oxidation product, the activity of indication MAO-A.
3. experimentation
(1) preparation of the thick enzyme of rat liver mitochondria monoamine oxidase, MAO (MAO): with Sprague-Dawley rat sacrificed by decapitation, get liver, with 4 ℃ of buffer (pH=7.6,0.2M sodium phosphate buffer) rinse well repeatedly, take by weighing 10g, shredding the back grinds, break into homogenate with the high speed dispersion device, the centrifugal 10min of 0.3M sucrose solution 3000rpm so that 1: 20 (w/v) adds pre-cooling gets supernatant, the centrifugal 30min of 10000rpm, get precipitation and be dissolved in the 40ml buffer, the high speed dispersion device is beaten even, divides to be filled to 40 pipes (1ml/ pipe), and measure protein content (biuret method) ,-80 ℃ of storages are standby.
(2) preparation of specimen solution: precision takes by weighing 56mg naringin reference substance, ultrasonic dissolution in the 10ml volumetric flask, standardize solution, from this titer, draw the solution of different volumes respectively, be mixed with the test solution of a series of variable concentrations, make its concentration that adds enzyme liquid and reagent one and reagent two back naringins be respectively 400,200,100,50,25,6.25,3.125 μ g/ml.
(3) MAO-A suppresses active assay method: add MAO-B type inhibitor 300 μ l pargyline pargyline (500nmol/L) to 30ml rat liver mitochondria enzyme, 37 ℃ of temperature are bathed half an hour, to suppress the activity of MAO-B.In measuring pipe, add each 0.3ml of a series of testing sample solutions successively, reagent one (benzylamine substrate liquid) 0.3ml, reagent two (pH7.6 Tris buffer) 3ml, and 0.6ml enzyme liquid, blank pipe is with physiologic saline for substitute enzyme liquid, and all the other are identical.Place 3h in 37 ℃ of water-baths, respectively add 10% after the taking-up and cross chloric acid 0.3ml, respectively add cyclohexane extraction 3.0ml, rotation mixing 2min on vortex mixer, centrifugation (2000r/min) 10min gets supernatant in quartz colorimetric utensil, returns to zero with blank, measure absorbance in the 242nm wavelength, measure the MAO-A activity.Enzymatic activity with the matched group that only adds unconstrained dose of substrate is 100%, calculates determinand to the active suppression ratio of MAO-A.
MAO-A maximum inhibition=(matched group absorbance-test group absorbance)/matched group absorbance * 100%
4. experimental result
Naringin sees Table 6 to the active inhibitory action of MAO-A.
Table 6 variable concentrations naringin is to the active inhibitory action of MAO-A
The result shows that the concentration that the MAO-A maximum inhibition is reached 50% o'clock naringin is 5.82 μ g/ml, has shown that it has the active effect of significant inhibition MAO-A, and the prompting naringin has antidepressant pharmacology activity.
With naringin and pharmaceutically acceptable through the aglycon of hydrolysis or enzymolysis generation and the Pharmaceutical composition that secondary glycosides is formed, can also comprise the preparation that becomes to use always with pharmaceutical carrier combined preparation pharmaceutically commonly used, as pharmaceutically acceptable dosage forms such as tablet, capsule, solution, suspension, injection, drip liquid.Can adopt oral, non-intestinal or topical routes.
Claims (2)
1. naringin or its pharmaceutically acceptable aglycon or the application of secondary glycosides in the preparation antidepressant drug through hydrolysis or enzymolysis generation.
2. purposes according to claim 1 is characterized in that: pharmaceutical dosage form is tablet, capsule, solution, suspension, injection, drip liquid or freeze-dried powder etc.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104825401A (en) * | 2015-04-22 | 2015-08-12 | 张永胜 | Dried orange peel extract freeze-dried powder injection and preparation method thereof |
| CN112661800A (en) * | 2021-03-15 | 2021-04-16 | 潍坊科技学院 | Naringin derivative, preparation method and application thereof in preparation of medicine for treating cardiovascular diseases |
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2009
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104825401A (en) * | 2015-04-22 | 2015-08-12 | 张永胜 | Dried orange peel extract freeze-dried powder injection and preparation method thereof |
| CN112661800A (en) * | 2021-03-15 | 2021-04-16 | 潍坊科技学院 | Naringin derivative, preparation method and application thereof in preparation of medicine for treating cardiovascular diseases |
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| CN101485674B (en) | 2011-05-18 |
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