Composition containing trace elements and application of composition in improvement of depression

Abstract

The invention discloses a composition containing trace elements and application of the composition to improvement of depression, and relates to the technical field of anti-depression products. The composition is prepared from the following raw materials: radix bupleuri, rhizoma acori graminei, radix paeoniae alba, hypericum monogynum, radix rehmanniae, stevia rebaudiana, radix saussureae lappae, semen boitae, common fenugreek seed, cortex cinnamomi, fresh ginger, liquorice root, magnesium oxide, zinc oxide, sodium selenite, probiotics, folic acid and pantothenic acid. Effective components of the traditional Chinese medicines are extracted, and the purpose of treating depression is achieved by means of soothing liver-qi stagnation, tonifying qi, promoting blood circulation and regulating blood, lowering lipid and blood sugar and the like; meanwhile, nutrient elements and trace elements are added into the traditional Chinese medicine extracts, so that the traditional Chinese medicine extracts have a synergistic effect, the depression-like behavior of mice can be effectively improved, the abnormal change of monoamine substances of the depression mice can be improved, and a relatively good depression treatment effect is shown.

Description

Technical Field

[0001] The invention relates to the technical field of antidepressant products, and more particularly to a composition containing trace elements and application thereof in improving depression. Background Art

[0002] Depression is a common chronic mental illness, characterized by persistent low mood, slow reaction, insomnia and poor tolerance. The results of the "Report on the Nutrition and Chronic Disease Status of Chinese Residents (2020)" show that the prevalence of depression in my country has reached 2.1%. The WHO has listed depression and insomnia as the world's number one disabling disease and the third largest disease in the world. As a highly disabling disease, depression has become a major public health problem in my country. It is estimated that by 2030, depressive disorders will become the disease with the highest disease burden in China. Because the pathogenesis of depression is very complex, the specific mechanism is still unclear so far, which poses a huge challenge to its treatment.

[0003] At present, the Western medicines used in clinical treatment of depression mainly include tricyclic antidepressants (TCAs, represented by drugs such as amitriptyline, doxepin, desipramine, etc.), monoamine oxidase inhibitors (MAOIs, represented by drugs such as moclobemide), selective serotonin reuptake inhibitors (SSRIs, represented by drugs such as fluoxetine hydrochloride, paroxetine, sertraline, etc.), serotonin and norepinephrine reuptake inhibitors (SNaRIs, represented by drugs such as venlafaxine), selective serotonin and norepinephrine reuptake inhibitors (NaSSAs, represented by drugs such as mirtazapine) and other types. For many years, tricyclic antidepressants and monoamine oxidase inhibitors have been widely used in the treatment of depression. However, due to relatively serious adverse reactions, such as tricyclic antidepressants blocking multiple neurotransmitter receptors, causing many side effects such as dry mouth, constipation, difficulty urinating, blurred vision, memory impairment and tachycardia, and monoamine oxidase inhibitors interacting with many drugs and specific foods, causing serious adverse reactions such as hypertensive crisis and acute yellow liver atrophy, domestic and foreign attention has begun to focus on developing ideal new antidepressant drugs from traditional Chinese medicine.

[0004] Studies have shown that macro, micro and trace elements are the main components for maintaining normal physiological functions of the brain, and depression is manifested as abnormal brain function, which is considered to be closely related to element imbalance. However, the existing technology only uses a single Chinese medicine to treat depression, and there are no reports on combining Chinese medicine with nutrients and trace elements to improve depression.

[0005] Therefore, how to provide a composition containing trace elements and apply it to improve depression is a problem that those skilled in the art need to solve urgently. Summary of the invention

[0006] In view of this, the present invention provides a composition containing trace elements and application thereof in improving depression.

[0007] In order to achieve the above object, the present invention adopts the following technical solution:

[0008] A composition containing trace elements, comprising: bupleurum, calamus, white peony root, hypericum, rehmannia root, stevia, aucklandia lappa, cypress seed, fenugreek, cinnamon bark, ginger, liquorice, magnesium oxide, zinc oxide, sodium selenite, folic acid and pantothenic acid.

[0009] Preferably, the composition is used as a medicine, health product or food for treating depression.

[0010] Furthermore, the composition also includes probiotics.

[0011] Preferably, the probiotics include one or more of bifidobacteria, lactobacilli and yeast;

[0012] Preferably, the viable count of the probiotics is 1×10 10 ×10 10 cfu / g.

[0013] Furthermore, the raw materials include, by weight: 40-50 parts of bupleurum, 35-45 parts of calamus, 32-40 parts of white peony root, 20-35 parts of hypericum, 22-35 parts of rehmannia, 20-30 parts of stevia, 20-30 parts of aucklandia lappa, 15-25 parts of pine nuts, 13-21 parts of fenugreek, 10-20 parts of cinnamon, 10-20 parts of ginger, 5-15 parts of licorice, 5-11 parts of magnesium oxide, 5-11 parts of zinc oxide, 5-11 parts of sodium selenite, 3-9 parts of probiotics, 1-6 parts of folic acid, and 1-6 parts of pantothenic acid.

[0014] Preferably, the raw materials include, by weight: 45 parts of bupleurum, 45 parts of calamus, 36 parts of white peony root, 20 parts of hypericum, 29 parts of rehmannia, 30 parts of stevia, 25 parts of aucklandia, 15 parts of cypress seeds, 17 parts of fenugreek, 20 parts of cinnamon, 15 parts of ginger, 5 parts of licorice, 8 parts of magnesium oxide, 11 parts of zinc oxide, 8 parts of sodium selenite, 3 parts of probiotics, 3 parts of folic acid, and 6 parts of pantothenic acid.

[0015] As the same inventive concept as the above technical solution, the present invention also claims a method for preparing the above composition, comprising the following steps:

[0016] (1) Weigh the raw materials according to the above weight parts and set aside;

[0017] (2) Crush the raw materials of Radix Bupleuri, Acorus calamus, Radix Rehmanniae, Radix Aucklandiae, Semen Platycladi, and Cinnamomum cassiae, and pass through a 40-50 mesh sieve to obtain a mixed powder A, and soak the mixed powder A in distilled water at a ratio of mixed powder: distilled water (m:v=1 g:6-10 mL), reflux extraction, combine the extracts, centrifuge, and dry under reduced pressure to obtain extract I;

[0018] (3) Grinding white peony root, Hypericum perforatum, stevia, fenugreek, ginger, and licorice raw materials, passing through a 60-80 mesh sieve to obtain a mixed powder B, adding the mixed powder B to n-butanol at a ratio of mixed powder B: n-butanol m:v=1 g:6-8 mL, stirring evenly, performing water bath ultrasonic extraction, filtering, centrifuging, and drying under reduced pressure to obtain extract II;

[0019] (4) Extract I and extract II are mixed, and magnesium oxide, zinc oxide, sodium selenite, probiotics, folic acid and pantothenic acid are added in sequence, mixed and homogenized, and dried under reduced pressure to obtain a composition.

[0020] Furthermore, in step (2), the soaking time is 40-60 min; the extraction times are 4-6 times, and the extraction time is 2-4 h / time; and the centrifugation is 600-800 rpm for 10-15 min.

[0021] Furthermore, in step (3), the water bath temperature is 50-60°C, the ultrasonic power is 800-1000W, the ultrasonic frequency is 40-60KHz, and the extraction time is 1-3h; and the centrifugation is 700-900rpm for 10-16min.

[0022] Furthermore, in step (4), the homogenization speed is 1100-1500 rpm, and the homogenization time is 8-15 min.

[0023] Furthermore, in steps (2)-(4), the reduced pressure drying is performed at 30-45°C for 60-72 hours.

[0024] As an inventive concept identical to the above technical solution, the present invention also requests protection for the use of the above composition or the composition prepared by the above method, wherein the use is to prepare a medicine, health product or food for improving depression.

[0025] As an inventive concept identical to the above technical solution, the present invention also seeks to protect a product for treating depression, wherein the product comprises the above composition.

[0026] It can be seen from the above technical solutions that, compared with the prior art, the present invention discloses a composition containing trace elements and its application in improving depression, with the following beneficial effects:

[0027] The present invention extracts effective ingredients from traditional Chinese medicines so that the components of the traditional Chinese medicines can act synergistically, thereby achieving the purpose of treating depression by soothing the liver and relieving depression, invigorating qi and replenishing qi, promoting blood circulation and regulating blood, and lowering blood lipids and blood sugar.

[0028] Since trace elements are closely related to depression, the destruction of their homeostasis can cause neurological dysfunction in patients, resulting in disorders in the body's material metabolism, insufficient brain energy supply, and mental disorders. Therefore, the present invention also adds trace elements (zinc, magnesium and selenium) and nutritional elements (folic acid and pantothenic acid) to the Chinese medicine extract, among which zinc is a trace element necessary for maintaining brain function, and its content is the highest in the human brain, especially in the hippocampus and cerebral cortex, which maintains the normal metabolism and regulation of the central nervous system, immune system, and enzymes. There are many zinc-containing enzymes in the human brain, which not only participate in the metabolic activities of brain tissue cells, but also participate in the balancing effect of neurotransmitters; magnesium is a coenzyme that participates in various biological processes in the brain and the fluidity of neuronal membranes, maintaining the stability of brain function. Supplementation of magnesium can change the composition of intestinal microorganisms in the human body and reduce the level of oxidative stress; selenium is an important component of the antioxidant glutathione peroxidase, selenium Element binding protein 1 (SBP-1) is an important medium and binding protein for selenium to exert biological activity in vivo. When the number of copies of the SBP-1 gene in brain tissue varies and the expression of SBP-1 in brain tissue is dysregulated, diseases such as schizophrenia and depression will occur. Therefore, adding selenium can reduce the level of oxidative stress and inflammatory response of the nervous system; folic acid is a coenzyme required for the synthesis of nucleic acids, which can assist cells in rapid division and growth, affecting normal cell division and replication; pantothenic acid coenzyme a and components of acyl carrier protein can participate in the metabolism of sugars, lipids and proteins, and are essential nutrients for the brain and nerves. It can increase the level of glutathione in the brain of hungry rats and reduce the oxidative stress response of hunger to rat brain tissue. Therefore, the present invention can show a good therapeutic effect of depression by applying trace elements, nutritional elements and the Chinese medicine extract of the present invention at the same time, and has an improvement effect on the depressive-like behavior of mice caused by chronic unpredictable stimulation, and can also regulate the levels of 5-HT and DA in the brain of depressed mice, improve the abnormal changes of monoamine substances in depressed mice, and balance the oxidative stress system in the brain of depressed mice.

[0029] Compared with commercially available Western antidepressant drugs, the pharmaceutical composition of the present invention has the advantages of mildness, few side effects and little irritation of traditional Chinese medicine, and the raw materials are easily available, the preparation process is mature, the preparation method is easy to control, safe and reliable, and the processing cost is low. DETAILED DESCRIPTION

[0030] The following will be described clearly and completely in conjunction with the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] Bupleurum: bitter in taste, slightly cold in nature, enters the liver and gallbladder meridians, has the effects of soothing the liver and relieving depression, clearing away heat and relieving exterior symptoms. The main active ingredient in Bupleurum is the triterpenoid saponin compound Bupleurosaponin, which can exert an antidepressant effect by increasing the content of monoamine neurotransmitters in the brain of depression model rats, activating the p-CREB / BDNF pathway, and inhibiting the apoptosis of hippocampal neurons.

[0032] Acorus calamus: It tastes spicy and bitter, is slightly warm in nature, and enters the heart, liver, and spleen meridians. It has the effects of calming the mind, improving intelligence, calming, lowering fever, relieving spasms, and anti-fungal.

[0033] White peony root: bitter and sour in taste, slightly cold in nature, enters the liver and spleen meridians, has the effects of regulating the immune system, sedation, anticonvulsant, analgesia, and cooling. White peony total glucosides can enhance the learning and short-term memory of normal mice.

[0034] Hypericum wilfordii: bitter in taste, warm in nature, enters the heart and liver meridians, has anti-depressant, sedative, antibacterial and anti-inflammatory, and trauma astringent effects.

[0035] Rehmannia: sweet and bitter in taste, cold in nature, enters the heart, liver and kidney meridians, has the effects of nourishing yin and kidney, nourishing blood and cooling blood.

[0036] Stevia: sweet in taste, cold in nature, enters the lung and stomach meridians, has the effects of regulating blood sugar and blood lipids, nourishing yin and promoting body fluid, eliminating fatigue, and nourishing essence and refreshing the mind.

[0037] Yunmuxiang: bitter, spicy, warm in nature, enters the spleen, stomach, large intestine, triple burner, and gallbladder meridians, has the effects of strengthening the stomach, relieving bloating, regulating qi and relieving depression;

[0038] Platycladus seed: sweet in taste, neutral in nature, enters the heart, kidney, and large intestine meridians, has the effects of nourishing the heart and calming the mind, moistening the intestines and promoting bowel movements, and stopping sweating.

[0039] Fenugreek: bitter in taste, warm in nature, enters the kidney meridian, has the effects of lowering blood sugar, lowering blood lipids, resisting gastric ulcers and tumors.

[0040] Cinnamon: It tastes spicy and is warm in nature. It enters the kidney, spleen, and bladder meridians. It has the effects of warming the middle and expelling cold, warming the meridians and relieving pain, and promoting blood circulation.

[0041] Ginger: It tastes spicy and is slightly warm in nature. It enters the lung, spleen, and stomach meridians. Its active ingredient, gingerol, can promote the secretion of insulin and quickly lower blood sugar when it interacts with human serotonin.

[0042] Licorice: sweet and neutral in taste, it enters the heart, lung, spleen, and stomach meridians, it can replenish qi and tonify the middle, clear away heat and detoxify, eliminate phlegm and relieve cough, relieve acute and acute pain, and harmonize various medicines. The substances in licorice also help control blood sugar.

[0043] Since glucose is the main energy source of the human brain, the ATP produced by glucose metabolism is the basis for maintaining the functions of neurons and non-neuronal cells in the brain, such as producing neurotransmitters and nerve impulses. And candies, beverages and candies contain a lot of sugar, and a high-sugar diet can affect the content of 5-hydroxytryptamine (5-HT) in the brain, as well as induce inflammation by changing the intestinal microbiome and intestinal permeability. Therefore, in the present invention, by adding raw materials with hypoglycemic effects, the blood sugar concentration of depressed patients can be suppressed, and the content of 5-hydroxytryptamine can be increased, thereby achieving the effect of improving depression.

[0044] Example 1

[0045] A composition containing trace elements, comprising, by weight, 40 parts of bupleurum, 40 parts of calamus, 40 parts of white peony root, 28 parts of hypericum, 22 parts of rehmannia root, 25 parts of stevia, 30 parts of aucklandia lappa, 20 parts of cypress seed, 13 parts of fenugreek, 15 parts of cinnamon bark, 20 parts of ginger, 10 parts of liquorice, 5 parts of magnesium oxide, 8 parts of zinc oxide, 11 parts of sodium selenite, 6 parts of probiotics, 1 part of folic acid, and 3 parts of pantothenic acid;

[0046] The preparation method is as follows:

[0047] (1) Weigh the raw materials according to the above weight parts and set aside;

[0048] (2) Crush the raw materials of Radix Bupleuri, Acorus calamus, Radix Rehmanniae, Radix Aucklandiae, Semen Platycladi, and Cinnamomum cassiae, and pass through a 40-mesh sieve to obtain a mixed powder A, add the mixed powder A into distilled water at a ratio of mixed powder: distilled water (m:v=1 g:8 mL), soak for 50 min, reflux extract for 6 times, each time for 3 h, combine the extracts, centrifuge at 600 rpm for 15 min, and dry under reduced pressure at 30° C. for 48 h to obtain extract I;

[0049] (3) The raw materials of white peony root, Hypericum, stevia, fenugreek, ginger and licorice were crushed and passed through a 60-mesh sieve to obtain a mixed powder B. The mixed powder B was added to n-butanol at a ratio of mixed powder B: n-butanol m:v = 1 g: 6 mL, and the mixture was stirred evenly. The mixture was extracted by water bath ultrasound at 50° C., 900 W, and 60 kHz for 1 h, filtered, centrifuged at 800 rpm for 16 min, and dried under reduced pressure at 38° C. for 36 h to obtain extract II.

[0050] (4) Extract I and Extract II were mixed, and magnesium oxide, zinc oxide, sodium selenite, and bifidobacterium (1.52×10 10cfu / g composition), yeast (1.06×10 10 cfu / g composition), folic acid and pantothenic acid were mixed, homogenized at 1100 rpm for 15 min, and dried at 45° C. under reduced pressure for 24 h to obtain a composition.

[0051] Example 2

[0052] A composition containing trace elements, comprising, by weight: 45 parts of bupleurum, 45 parts of calamus, 36 parts of white peony root, 20 parts of hypericum, 29 parts of rehmannia root, 30 parts of stevia, 25 parts of aucklandia lappa, 15 parts of cypress seed, 17 parts of fenugreek, 20 parts of cinnamon bark, 15 parts of ginger, 5 parts of liquorice, 8 parts of magnesium oxide, 11 parts of zinc oxide, 8 parts of sodium selenite, 3 parts of probiotics, 3 parts of folic acid, and 6 parts of pantothenic acid;

[0053] The preparation method is as follows:

[0054] (1) Weigh the raw materials according to the above weight parts and set aside;

[0055] (2) Crush the raw materials of Radix Bupleuri, Acorus calamus, Radix Rehmanniae, Radix Aucklandiae, Semen Platycladi, and Cinnamomum cassiae, and pass through a 45-mesh sieve to obtain a mixed powder A, add the mixed powder A into distilled water at a ratio of mixed powder: distilled water (m:v=1 g:6 mL), soak for 60 min, reflux extract 5 times, each time for 2 h, combine the extracts, centrifuge at 700 rpm for 13 min, and dry under reduced pressure at 38° C. for 36 h to obtain extract I;

[0056] (3) Pulverize white peony root, Hypericum perforatum, stevia, fenugreek, ginger, and licorice raw materials, pass through a 70-mesh sieve to obtain a mixed powder B, add the mixed powder B to n-butanol at a ratio of mixed powder B: n-butanol m:v = 1 g: 8 mL, stir evenly, extract by water bath ultrasonic extraction at 55° C., 1000 W, 40 kHz for 2 h, filter, centrifuge at 700 rpm for 13 min, and dry under reduced pressure at 45° C. for 24 h to obtain extract II;

[0057] (4) Extract I and Extract II were mixed, and magnesium oxide, zinc oxide, sodium selenite, and lactobacillus (1.24×10 10 cfu / g composition), Bifidobacterium (1.52×10 10 cfu / g composition), folic acid and pantothenic acid were mixed, homogenized at 1350 rpm for 12 min, and dried at 30° C. under reduced pressure for 48 h to obtain a composition.

[0058] Example 3

[0059] A composition containing trace elements, comprising, by weight, 50 parts of bupleurum, 35 parts of calamus, 32 parts of white peony root, 35 parts of hypericum, 35 parts of rehmannia root, 20 parts of stevia, 20 parts of aucklandia lappa, 25 parts of cypress seed, 21 parts of fenugreek, 10 parts of cinnamon, 10 parts of ginger, 15 parts of liquorice, 11 parts of magnesium oxide, 5 parts of zinc oxide, 5 parts of sodium selenite, 9 parts of probiotics, 6 parts of folic acid, and 1 part of pantothenic acid;

[0060] The preparation method is as follows:

[0061] (1) Weigh the raw materials according to the above weight parts and set aside;

[0062] (2) Crush the raw materials of Radix Bupleuri, Acorus calamus, Radix Rehmanniae, Radix Aucklandiae, Semen Platycladi, and Cinnamomum cassiae, and pass through a 50-mesh sieve to obtain a mixed powder A, add the mixed powder A into distilled water at a ratio of mixed powder: distilled water (m:v=1 g:10 mL), soak for 40 min, reflux extract 4 times, each time for 4 h, combine the extracts, centrifuge at 800 rpm for 10 min, and dry under reduced pressure at 45° C. for 24 h to obtain extract I;

[0063] (3) The raw materials of white peony root, Hypericum, stevia, fenugreek, ginger and licorice were crushed and passed through an 80-mesh sieve to obtain a mixed powder B, and the mixed powder B was added to n-butanol at a ratio of mixed powder B: n-butanol m:v = 1 g: 6 mL, and the mixture was stirred evenly. The mixture was extracted by water bath ultrasonication at 60° C., 800 W, and 50 kHz for 2 h, filtered, centrifuged at 900 rpm for 10 min, and dried under reduced pressure at 30° C. for 48 h to obtain extract II;

[0064] (4) Extract I and Extract II were mixed, and magnesium oxide, zinc oxide, sodium selenite, and lactobacillus (1.24×10 10 cfu / g composition), yeast (1.06×10 10 cfu / g composition), folic acid and pantothenic acid were mixed, homogenized at 1500 rpm for 8 min, and dried under reduced pressure at 38° C. for 36 h to obtain a composition.

[0065] Experimental Example Evaluation of the effects of different compositions on depressive-like behaviors in CUMS depression model mice

[0066] (1) Experimental animal grouping and drug administration

[0067] 160 C57BL / 6J male mice (weight 16-18g, SPF grade) were randomly divided into 8 groups, 20 mice in each group, including blank group, model group, fluoxetine group, low-dose combination group, medium-dose combination group, high-dose combination group, test group A, and test group B;

[0068] The model group was injected with the same volume of solvent as the treatment group, the fluoxetine group was given a dose of 20 mg / kg, the composition used in the experiment was prepared by Example 2, the low-dose group of the composition was given a dose of 10 mg / kg, the medium-dose group of the composition was given a dose of 20 mg / kg, the high-dose group of the composition was given a dose of 40 mg / kg, the test A and B groups were given a dose of 20 mg / kg, and the solvent was 0.9% sodium chloride solution;

[0069] Among them, the test group A is based on the composition of Example 2, but magnesium oxide, zinc oxide, sodium selenite, probiotics, folic acid and pantothenic acid are removed, and the rest are the same;

[0070] The experimental group B is a composition in patent number CN104435100A, wherein the weight percentage of each raw material in the composition is 10% zinc oxide, 10% folic acid, 63% probiotics, 10% okra juice, 2% perilla leaf juice and 5% water chestnut powder; the probiotics include bifidobacterium, lactobacillus, lactococcus, thermophilic streptococcus, acetic acid lactic acid streptococcus and yeast, and the total probiotics are not less than 1×10 10 cfu.

[0071] (2) Establishment of the chronic unpredictable stimulation model (CUMS) in mice

[0072] After the experimental mice adapted for 3 days, except for the normal group, the other groups were kept in solitary mode and randomly given 1-2 stimulations every day to replicate the chronic stress depression model. The stimulations included fasting (12h), water deprivation (12h), day and night reversal (12h / 12h), cold water swimming (4℃, 5min), hot water swimming (45℃, 5min), tilted mouse cage (45°, 12h), wet bedding (12h), restraint (12h), tail clamping (2min at 1cm from the tip of the tail), electric shock to the sole of the foot (1min), and shock. The same stimulation factors appeared discontinuously and were received continuously for 35 days. Drug administration began in the first week of modeling, and the administration time was 9:00 am every day, and the drug administration was continued for 5 weeks.

[0073] (3) Sugar water preference test

[0074] Before modeling, mice were trained to adapt to 1% sucrose water in a quiet environment. Mice were housed in single cages, and two identical water bottles were placed in each cage. In the first 24 hours, both bottles were filled with 1% sucrose water; in the second 24 hours, one bottle was filled with 1% sucrose water and one bottle was filled with pure water, and then the two bottles of water were taken away and weighed. Before the experiment and in the fifth week of the experiment, each mouse was subjected to a sugar water preference test. Before the experiment, the mice were fasted and deprived of water for 24 hours, and then given two bottles of water that were predetermined in advance: one bottle was 1% sucrose water and the other was pure water. After 24 hours, the mice were taken away and weighed, and the consumption of sucrose water and pure water was recorded, and the sugar water preference rate was calculated. The results are shown in Table 1.

[0075] Sugar water preference rate = (sugar water consumption / total liquid consumption) × 100%.

[0076] Table 1 Effects of different compositions on the sugar water preference rate of mice

[0077]

[0078]

[0079] As can be seen from Table 1, 5 weeks after modeling, the sugar preference rate of mice in the CUMS model group decreased and was significantly lower than that of the blank group mice. After treatment with the composition of Example 2 of the present invention, the sugar preference rate of mice in each group increased, among which the medium-dose group and the high-dose group of the composition showed better effects than the fluoxetine group. It can be seen that after CUMS modeling, the mice showed depressive-like behavioral symptoms, which were manifested as a significant decrease in the sugar preference rate, indicating that the CUMS depression model was successfully established. After treatment with the composition group, the depressive-like behavior of the CUMS mouse model was significantly alleviated, indicating that the composition of the present invention has an intervention effect on the CUMS mouse model, among which the medium-dose group of the composition showed the best effect; the trace elements and nutrients were removed from the test group A. Although the sugar preference rate of mice after administration was lower than that of the composition group, it was close to the sugar preference rate of mice after administration of the fluoxetine group, which shows that there is a synergistic effect between the trace elements and nutrients and the Chinese medicine composition of the present invention, and the synergistic effect can significantly alleviate the depressive-like behavior of the CUMS mouse model; the test group B is a composition in the prior art, which can also increase the sugar preference rate of mice, but it is significantly lower than the composition of the present invention.

[0080] (4) Forced swimming test

[0081] The mice were placed in a glass cylinder 24 cm high and 15 cm in diameter and forced to swim for 6 min at a water temperature of (25±1)°C. The cumulative immobility time of the mice within the next 4 min was observed and recorded. The cumulative immobility time was when the mice stopped struggling, floated in the water and remained motionless, or only made some necessary slight movements to keep their heads floating on the water. The measurement results are shown in Table 2.

[0082] Table 2 Effects of different compositions on the immobility time of mice forced swimming

[0083]

[0084]

[0085] As shown in Table 2, compared with the blank group, the duration of the forced swimming immobility of the mice in the model group was significantly different, indicating that the model was successfully established; compared with the model group, the duration of the forced swimming immobility of the mice in each dose group of the composition of the present invention was significantly reduced; compared with the fluoxetine group, the medium and high dose groups of the composition of the present invention can significantly reduce the duration of the forced swimming immobility of the mice; in the test group A, trace elements and nutrients were removed, and although the duration of the forced swimming immobility of the mice after administration was higher than that of the composition group, it was lower than that of the model group, indicating that there is a synergistic effect between the trace elements and nutrients and the Chinese medicine composition of the present invention, and the synergistic effect can significantly reduce the duration of the forced swimming immobility of the mice, thereby improving depression; although the test group B can also reduce the duration of the forced swimming immobility of the mice, the reduction effect is lower than that of the composition of the present invention.

[0086] (5) Tail suspension test

[0087] The mouse's tail (about 1 cm from the tip of the tail) was fixed on a homemade tail suspension device (made of opaque material, a cube with a length, width and height of 40 cm, fixed with a small wooden clip on an iron stand), so that the mouse's head was about 10 cm from the bottom of the box. The mouse's activity was observed within 6 minutes, and the cumulative immobility time of the mouse in the last 4 minutes was recorded and the average value was calculated. The measurement results are shown in Table 3.

[0088] Table 3 Effects of different compositions on the tail suspension immobility time of mice

[0089]

[0090]

[0091] As shown in Table 3, compared with the blank group, the immobility time of the tail suspension of mice in the model group was significantly increased; compared with the model group, the immobility time of the tail suspension of mice in each dose group of the composition of the present invention was significantly reduced; compared with the fluoxetine group, the medium and high dose groups of the composition of the present invention can significantly reduce the immobility time of the tail suspension of mice; although the immobility time of the tail suspension of mice in the test A group after administration was higher than that of the composition group, it was lower than that of the model group, which shows that there is a synergistic effect between the trace elements and nutrients and the Chinese medicine composition of the present invention, and the synergistic effect can significantly reduce the immobility time of the tail suspension of mice; although the test B group can also reduce the immobility time of the tail suspension of mice, the reduction effect is lower than that of the composition of the present invention.

[0092] (6) Effects of different compositions on 5-HT, DA and CORT levels in mouse serum

[0093] On the day after the last administration, the eyeballs of the mice were removed and blood was collected. The blood was centrifuged at 3500 r / min for 10 min, and the supernatant was collected. The levels of 5-HT, DA and CORT in the serum were detected according to the instructions of the ELISA kit. The results are shown in Table 4.

[0094] Table 4 Effects of different compositions on 5-HT, DA and CORT levels in mouse serum

[0095]

[0096]

[0097] Monoamine neurotransmitters include 5-HT, DA, dopamine, etc. These neurotransmitters mainly affect human mental activities, emotional reactions, learning and memory and other functions. As shown in Table 4, compared with the blank group, the 5-HT and DA levels in the serum of the model group mice were significantly reduced, and the CORT level was significantly increased; compared with the model group, the 5-HT and DA levels in the serum of the low, medium and high dose groups of the composition and the fluoxetine group mice were significantly increased, and the CORT level was significantly reduced; compared with the model group, the 5-HT and DA levels in the serum of the mice in the test A and B groups were increased, and the CORT level was reduced, but the effect was lower than that of the composition of the present invention. It can be seen that the composition of the present invention can regulate the 5-HT and DA levels in the brain of depressed mice and improve the abnormal changes of monoamine substances in depressed mice.

[0098] (7) Effects of different compositions on glutathione, malondialdehyde and superoxide dismutase activity in mouse brain tissue

[0099] After the experiment, the mice were decapitated and their brains were removed. The contents of glutathione (GSH) and malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the brain tissues of the mice were determined by enzyme-linked immunosorbent assay. The results are shown in Table 5.

[0100] Table 5 Effects of different compositions on glutathione, malondialdehyde content and superoxide dismutase activity in mouse brain tissue

[0101]

[0102]

[0103] Since brain tissue is very sensitive to damage caused by oxygen free radicals, excessive accumulation of oxygen free radicals can easily cause oxidative damage to the body, and this damage may cause mental disorders, so activation of the oxidative stress system may be one of the important reasons for cognitive impairment in patients with depression, among which SOD is an important free radical scavenger in the body, and its function is affected, which is an important reason for the accumulation of a large number of free radicals; the content of GSH and MDA directly represents the level of oxidative stress in the mouse brain. As shown in Table 5, compared with the blank group, the MDA content in the model group mouse brain was significantly increased, the GSH content was significantly reduced, and the SOD activity was significantly reduced; compared with the model group, the MDA content in the low, medium, and high dose groups of the composition and the fluoxetine group mouse brain was significantly reduced, and the GSH content and SOD activity were significantly increased; compared with the model group, the MDA content in the mouse brain of the test A and B groups was reduced, and the GSH content and SOD activity were increased, but the effect was lower than the composition of the present invention. It can be seen from this that the oxidative stress system in the brain of depressed mice is significantly unbalanced, and after the composition of the present invention is given for intervention treatment, its oxidative stress system is improved.

[0104] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0105] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A composition containing trace elements, characterized in that: Includes the following ingredients: Bupleurum, Acorus calamus, White Peony Root, Hypericum, Rehmannia glutinosa, Stevia, Aucklandia lappa, Platycladus orientalis, Fenugreek, Cinnamon, Ginger, Licorice, Magnesium Oxide, Zinc Oxide, Sodium Selenite, Folic Acid and Pantothenic Acid; Preferably, the composition is used as a medicine, health product or food for treating depression.

2. The composition according to claim 1, characterized in that Also includes: Probiotics; Preferably, the probiotics include one or more of bifidobacteria, lactobacilli and yeast; Preferably, the viable count of the probiotics is 1×10 10 ×10 10 cfu / g.

3. The composition according to any one of claims 1-2, characterized in that The raw materials include, by weight: 40-50 parts of bupleurum, 35-45 parts of calamus, 32-40 parts of white peony root, 20-35 parts of hypericum, 22-35 parts of rehmannia root, 20-30 parts of stevia, 20-30 parts of aucklandia lappa, 15-25 parts of cypress seed, 13-21 parts of fenugreek, 10-20 parts of cinnamon bark, 10-20 parts of ginger, 5-15 parts of liquorice, 5-11 parts of magnesium oxide, 5-11 parts of zinc oxide, 5-11 parts of sodium selenite, 3-9 parts of probiotics, 1-6 parts of folic acid, and 1-6 parts of pantothenic acid; Preferably, the raw materials include, by weight: 45 parts of bupleurum, 45 parts of calamus, 36 parts of white peony root, 20 parts of hypericum, 29 parts of rehmannia, 30 parts of stevia, 25 parts of aucklandia, 15 parts of cypress seeds, 17 parts of fenugreek, 20 parts of cinnamon, 15 parts of ginger, 5 parts of licorice, 8 parts of magnesium oxide, 11 parts of zinc oxide, 8 parts of sodium selenite, 3 parts of probiotics, 3 parts of folic acid, and 6 parts of pantothenic acid.

4. A method for preparing a composition containing trace elements according to any one of claims 2-3, characterized in that: The following steps are involved: (1) Weigh the raw materials according to the above weight parts and set aside; (2) Crush the raw materials of Radix Bupleuri, Acorus calamus, Radix Rehmanniae, Radix Aucklandiae, Semen Platycladi, and Cinnamomum cassiae, and pass through a 40-50 mesh sieve to obtain a mixed powder A, and soak the mixed powder A in distilled water at a ratio of mixed powder: distilled water (m:v=1 g:6-10 mL), reflux extraction, combine the extracts, centrifuge, and dry under reduced pressure to obtain extract I; (3) Grinding white peony root, Hypericum perforatum, stevia, fenugreek, ginger, and licorice raw materials, passing through a 60-80 mesh sieve to obtain a mixed powder B, adding the mixed powder B to n-butanol at a ratio of mixed powder B: n-butanol m:v=1 g:6-8 mL, stirring evenly, performing water bath ultrasonic extraction, filtering, centrifuging, and drying under reduced pressure to obtain extract II; (4) Extract I and extract II are mixed, and magnesium oxide, zinc oxide, sodium selenite, probiotics, folic acid and pantothenic acid are added in sequence, mixed and homogenized, and dried under reduced pressure to obtain a composition.

5. The preparation method according to claim 4, characterized in that: In step (2), the soaking time is 40-60 minutes; the extraction times are 4-6 times, and the extraction time is 2-4 hours per time; and the centrifugation is performed at 600-800 rpm for 10-15 minutes.

6. The preparation method according to claim 4, characterized in that: In step (3), the water bath temperature is 50-60°C, the ultrasonic power is 800-1000W, the ultrasonic frequency is 40-60KHz, and the extraction time is 1-3h; the centrifugation is 600-800rpm for 10-16min.

7. The preparation method according to claim 4, characterized in that: In step (4), the homogenization speed is 1100-1500 rpm, and the homogenization time is 8-15 min.

8. The preparation method according to claim 4, characterized in that: In steps (2)-(4), the reduced pressure drying is performed at 30-45°C for 60-72 hours.

9. The use of the composition according to any one of claims 1 to 3, characterized in that: The use is to prepare anti-depression medicines, health products or foods.

10. A product for treating depression, characterized in that: The product comprises the composition according to any one of claims 1 to 3.

Images