Composition with effects of improving depression and stress, preparation method and application thereof

Abstract

The present invention discloses a composition having the effect of improving depression and stress, as well as its preparation method and application. The composition is prepared from the following raw materials in parts by weight: 1-10 parts of oyster, 0.5-5 parts of dried tangerine peel, 0.5-5 parts of poria cocos, 0.1-1 parts of ginseng, 0.2-2 parts of rose, 0.5-5 parts of polygonatum, 0.5-5 parts of wolfberry, 0.5-5 parts of cassia seed, 0.5-5 parts of chrysanthemum, 0.01-0.1 parts of phosphatidylserine, and 0.01-0.1 parts of taurine. The composition provided by the present invention can improve depression and stress and can be used to prepare antidepressant drugs.

Description

Technical Field

[0001] The present invention relates to a composition, in particular to a composition capable of improving depression and stress and a preparation method thereof. Background Art

[0002] Depression is a condition characterized by a significant and persistent low mood, often accompanied by insomnia, memory loss, eating disorders, and other symptoms. In severe cases, it can lead to suicidal thoughts and behaviors. According to the World Health Organization, depression is the fourth most common illness worldwide. Depressed individuals experience difficulty adapting to society and have decreased attention span, placing them at high risk for suicide. The specific pathogenesis of depression mainly includes the following hypotheses: (1) Stress hypothesis: Continuous stress leads to continuous activation of the hypothalamic-pituitary-adrenal (HPA) axis, increased release of cortisol, acting on the glucocorticoid receptors of hippocampal neurons, ultimately damaging the hippocampal tissue and leading to neuronal and glial cell necrosis; (2) Monoamine neurotransmitter regulation disorder hypothesis: The reuptake of neurotransmitters 5-hydroxytryptamine, norepinephrine, and dopamine in the synaptic cleft of neurons increases, the content decreases, and nerve conduction is blocked; (3) Neurotrophic factor regulation disorder hypothesis: Depressed patients lack nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex, resulting in nerve cell atrophy and impaired neural plasticity; (4) Central nervous system inflammation hypothesis: The expression of inflammatory factors IL-1β, IL-6, and TNF-α in the brains of depressed patients increases, activating HPA hyperfunction and exacerbating depression. In addition, inflammatory factors can activate the tryptophan-kynurenine pathway, leading to excessive degradation of norepinephrine and 5-hydroxytryptamine. At the same time, the quinolinic acid produced by the activation of the pathway can excite NMDA receptors, causing neurotoxicity and damaging hippocampal neurons. (5) The "brain-gut" axis disorder hypothesis: The HPA axis in patients with depression is hyperfunctional, and increased CRF will lead to increased permeability of the intestinal mucosal wall, causing intestinal pathogens to translocate to the mesenteric lymph nodes or circulatory system, activate macrophages, and produce a large number of inflammatory factors. They enter the macrocirculation and are carried into the brain by the corresponding inflammatory factor transporters on the blood-brain barrier, activating microglia, and then producing a large number of inflammatory factors, inducing central nervous system inflammation. Intestinal inflammation can also activate the tryptophan-kynurenine metabolic pathway, causing tryptophan from food to be metabolized into pro-inflammatory substances such as kynurenic acid and quinolinic acid, reducing the relative content of tryptophan, an important synthetic precursor of 5-hydroxytryptamine, resulting in insufficient synthesis of central 5-hydroxytryptamine. The "brain-gut" axis imbalance hypothesis combines the excessive hyperactivity of the HPA axis with central nervous system inflammation, and has therefore become an important hotspot in depression research. (6) The neural excitation / inhibition imbalance hypothesis: This hypothesis holds that chronic stress continuously activates the hypothalamic-pituitary-adrenal (HPA) axis of the limbic system in the brain, prompting excessive release of glucocorticoids, leading to excessive excitation of Glu neurons in the prefrontal cortex and hippocampus. Excessive Glu release leads to downregulation of postsynaptic AMPA glutamate receptors, loss of dendritic spines, and dendritic atrophy. Even if the stress subsides, Glu synapses cannot recover in the short term, LTP cannot be formed, and synaptic plasticity is severely impaired.Glu neurotoxicity also leads to atrophy of GABAergic interneurons, weakening their ability to inhibit excessive HPA axis activation and exacerbating this vicious cycle. This ultimately impairs synaptic plasticity, reduces connectivity between the prefrontal cortex and the limbic system, particularly the hippocampus, and compromises neural circuit integrity, leading to the development and progression of depression. Numerous hypotheses have suggested that depression is a complex emotional disorder, with persistent HPA activation induced by stress as a core component. Existing medications for depression, including tricyclic antidepressants such as imipramine, serotonin reuptake inhibitors such as fluoxetine, and monoamine oxidase inhibitors such as phenelzine, all target the neurotransmitter concentration in the synaptic cleft and inhibit its reuptake. This results in 30% of depression patients being resistant to existing medications. More seriously, long-term use of some antidepressants, such as fluoxetine, can increase suicidal tendencies in patients. The newly marketed esketamine has also attracted controversy due to its hallucinogenic effects and potential addictiveness. Summary of the Invention

[0003] Objectives of the invention: The present invention aims to provide a composition with reliable efficacy, good safety, and excellent ability to improve depression and stress. Another objective of the present invention is to provide a method for preparing and using the composition.

[0004] Technical solution: In order to achieve the above objectives, the technical solution adopted by the present invention is:

[0005] A composition with the effect of improving depression and stress comprises the following raw materials in parts by weight: 1-10 parts of oyster, 0.5-5 parts of dried tangerine peel, 0.5-5 parts of poria cocos, 0.1-1 parts of ginseng, 0.2-2 parts of rose, 0.5-5 parts of polygonatum, 0.5-5 parts of wolfberry, 0.5-5 parts of cassia seed, 0.5-5 parts of chrysanthemum, 0.01-0.1 parts of phosphatidylserine, and 0.01-0.1 parts of taurine.

[0006] As a preferred embodiment, the above-mentioned composition for improving depression and stress comprises the following raw materials in parts by weight: 2-5 parts of oyster, 1-4 parts of dried tangerine peel, 1-4 parts of poria, 0.2-0.5 parts of ginseng, 0.5-1.5 parts of rose, 1-4 parts of polygonatum, 1-4 parts of wolfberry, 1-4 parts of cassia seed, 1-4 parts of chrysanthemum, 0.02-0.05 parts of phosphatidylserine, and 0.02-0.05 parts of taurine.

[0007] As a preferred embodiment, the above composition for improving depression and stress comprises the following raw materials in parts by weight: 5 parts of oyster, 1 part of dried tangerine peel, 2 parts of poria, 0.4 parts of ginseng, 1 part of rose, 2 parts of polygonatum, 3 parts of wolfberry, 2 parts of cassia seed, 2 parts of chrysanthemum, 0.02 parts of phosphatidylserine, and 0.1 parts of taurine.

[0008] As a preferred embodiment, the above composition for improving depression and stress comprises the following raw materials in parts by weight: 3 parts of oyster, 3 parts of dried tangerine peel, 1 part of poria, 0.3 parts of ginseng, 3 parts of rose, 0.5 parts of polygonatum, 2 parts of wolfberry, 1 part of cassia seed, 3 parts of chrysanthemum, 0.06 parts of phosphatidylserine, and 0.03 parts of taurine.

[0009] As a preferred embodiment, the above composition for improving depression and stress comprises the following raw materials in parts by weight: 2 parts of oyster, 1 part of dried tangerine peel, 1.5 parts of poria, 0.5 part of ginseng, 0.5 part of rose, 1.5 parts of polygonatum, 1 part of wolfberry, 1 part of cassia seed, 1 part of chrysanthemum, 0.05 part of phosphatidylserine, and 0.05 part of taurine.

[0010] The innovation of the present invention is:

[0011] Traditional Chinese Medicine (TCM) often categorizes depression as "depression," "insomnia," "forgetfulness," "epilepsy," "lily disease," and "plum pit qi." TCM believes that depression is often caused by emotional damage, resulting in disharmony between the qi, blood, yin and yang of the five internal organs, and a negative impact on the brain. While emotional factors are the cause of depression, "weak internal qi" is a key internal factor in its onset. The disease is located in the brain, affecting the five internal organs, primarily the heart, liver, spleen, and kidneys. Initially, symptoms of either excess or deficiency are common, but over time, a mixture of both deficiency and excess is common. Primary deficiency is primarily characterized by liver and kidney yin deficiency, kidney essence deficiency, and heart and spleen deficiency; secondary excess is primarily characterized by liver depression, qi stagnation, turbid phlegm, and blood stasis.

[0012] Chronic stress, anxiety, or frightening experiences can damage kidney essence. Prolonged depression can lead to persistent, lingering exacerbations of qi, blood stasis, and phlegm-dampness, affecting the kidneys. This excess leads to deficiency, resulting in kidney-essence deficiency. The kidneys regulate bone formation and produce marrow, which then replenishes the brain. Brain marrow is the material foundation for the brain's functioning. Therefore, kidney-essence deficiency can lead to poor nourishment of the brain, resulting in symptoms of low mood, pessimism, loss of interest, laziness, and a weakened will. The liver and kidneys share a common origin. Kidney-essence deficiency prevents water from containing wood, impairing the liver's ability to disperse qi, and hinders the smooth flow of qi. This deficiency leads to excess, resulting in liver-qi stagnation. Over time, liver-qi stagnation transforms into fire, which then coalesces with water and dampness, transforming into damp-heat that accumulates in the liver and gallbladder, causing liver-gallbladder damp-heat syndrome. When dampness and heat coexist, the liver and gallbladder function abnormally, causing restlessness, irritability, insomnia and nightmares; when dampness and heat are blocked, the spleen and stomach cannot ascend and descend properly, the production of qi and blood is insufficient, and the heart is not nourished, causing palpitations, timidity, insomnia and forgetfulness. Ultimately, a mixed depression syndrome is formed, with kidney essence deficiency as the root and qi stagnation as the symptom. Treatment should pay attention to distinguishing yin and yang, deficiency and excess, and focus on the method of taking both deficiency and excess into consideration. For deficiency syndrome, nourish the heart, strengthen the spleen, nourish the liver, and tonify the kidney. For excess syndrome, regulate qi and relieve depression, activate blood to clear heat, and resolve phlegm and dampness.

[0013] The Shuyu Jieya prescription is based on the aforementioned analysis of the etiology and pathogenesis of depression, combined with clinical experience in Traditional Chinese Medicine. It consists of wolfberry, polygonatum, cassia seed, ginseng, poria, malt, tangerine peel, rose, oyster, and chrysanthemum. In this prescription, wolfberry nourishes the liver and kidneys, replenishing essence and marrow; polygonatum tonifies spleen qi and benefits kidney yin; and cassia seed nourishes the liver and kidneys. Together, these three herbs replenish kidney essence. Ginseng replenishes the qi of the five internal organs, helping kidney essence transform into qi and blood, nourishing the liver while also nourishing the heart and calming the mind. Ginseng also nourishes the spleen, while poria dissipates dampness and strengthens the spleen, calming the mind and tranquilizing the mind. Malt soothes the liver and eliminates stagnation, tangerine peel soothes the liver and regulates qi, and rose soothes the liver, activating blood circulation, and removing blood stasis. Together, these four herbs unblock liver qi and restore the spleen and stomach's transport and transformation functions, while also preventing the greasy, stomach-nourishing effects of wolfberry and polygonatum. Oyster calms the mind, suppresses yang and replenishes yin, and also resolves phlegm and nourishes yin. Chrysanthemum, with its ascending and dispersing properties, helps other herbs ascend. It also works with oyster and cassia seed to clear the liver and resolve internal heat, while also preventing ginseng's warming and drying effects from damaging yin. This comprehensive formula addresses both the symptoms and the root cause, simultaneously tonifying and purging. It replenishes the body without hindering pathogenic factors, and dispels pathogenic factors without harming the body's health. The synergistic effects of these herbs can invigorate qi and nourish yin, resolve phlegm and blood stasis, and calm the mind. Furthermore, incorporating phosphatidylserine, which promotes dopamine secretion, and taurine, which combats fatigue and improves the core symptoms of depression, further enhances the antidepressant effect.

[0014] The method for preparing the composition for improving depression and stress of the present invention comprises the following steps:

[0015] (1) Take wolfberry, polygonatum, cassia seed, ginseng, poria, malt, tangerine peel, rose, oyster, and chrysanthemum according to weight, add 5 to 15 times the weight of the medicinal materials in water, reflux extract 2 to 3 times, each time for 1 to 2 hours, filter, and combine the filtrates;

[0016] (2) The filtrate of step (1) was concentrated under reduced pressure, and phosphatidylserine and taurine were added according to weight to prepare a composition.

[0017] As a preferred embodiment, the reflux extraction conditions in step (1) are as follows: first, add 10 times the volume of water by weight of the medicinal material, and reflux extract at 160°C for 90 minutes. Second and third times, add 8 times the volume of water by weight of the medicinal material, and reflux extract at 160°C for 60 minutes.

[0018] Beneficial Effects: The composition provided by the present invention was obtained through screening based on clinical experience in Traditional Chinese Medicine. In animal models, it significantly alleviated depressive-like behaviors, inhibited HPA axis activation induced by stress, increased the supply of neurotransmitters and neurotrophic factors in the brain, and inhibited central nervous system inflammation. These studies have shown that the traditional Chinese medicine composition provided by the present invention has a significant effect on improving depressive mood and can also effectively improve HPA axis activation induced by stress. It can be used to prepare a drug that improves depression and stress.

[0019] The composition of the present invention is used in improving depression and stress. The composition and a pharmaceutically acceptable carrier are prepared into tablets, pills, powders, decoctions, granules, decoctions or extracts, which are convenient for clinical use. In addition, the composition provided by the present invention has no obvious toxic and side effects, can be taken for a long time, and has good safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a bar graph showing the effect of the composition on the immobility time of tail-suspended mice.

[0021] Figure 2 The figure is a bar graph showing the effect of the ingredient combination on the immobility time of forced swimming mice.

[0022] Figure 3 The bar graph shows the effect of the composition on the sugar preference index of chronic stress-induced depression mice.

[0023] Figure 4 The bar graph shows the effect of the composition on the stress factors in the serum of chronic stress-induced depression mice.

[0024] Figure 5 The bar graph shows the effect of the composition on neurotransmitters in the brains of mice with chronic stress and depression.

[0025] Figure 6 It is a bar graph showing the effect of the composition on neurotrophic factors in the hippocampus of chronic stress-induced depression mice.

[0026] Figure 7 This is a bar graph showing the effects of the composition on inflammatory factors in the hippocampus of chronic stress-induced depression mice. DETAILED DESCRIPTION

[0027] The present invention is further illustrated below with reference to specific examples. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, modifications of various equivalent forms of the present invention made by those skilled in the art all fall within the scope defined by the claims attached to this application.

[0028] Example 1 A method for preparing a Chinese medicine composition comprises the following steps:

[0029] (1) Accurately weigh 5 parts of oyster, 1 part of dried tangerine peel, 2 parts of poria, 0.4 parts of ginseng, 1 part of rose, 2 parts of polygonatum, 3 parts of wolfberry, 2 parts of cassia seed, and 2 parts of chrysanthemum. Add 10 times the weight of the herbs in water and reflux extract for 90 minutes. Filter and collect the filtrate and residue.

[0030] (2) Take the medicinal residue in step (1), add 8 times the volume of water by weight of the medicinal material, reflux and extract for 60 minutes, filter, and collect the filtrate.

[0031] (3) Take the medicinal residue in step (2), add 8 times the volume of water by weight of the medicinal material, reflux and extract for 60 minutes, filter, and collect the filtrate.

[0032] (4) The filtrates obtained in step (1), step (2) and step (3) were combined and concentrated under reduced pressure to obtain an extract, and 0.02 parts of phosphatidylserine and 0.1 parts of taurine were added to prepare a composition.

[0033] Example 2 A method for preparing a Chinese medicine composition comprises the following steps:

[0034] (1) Accurately weigh 3 parts of oyster, 3 parts of dried tangerine peel, 1 part of poria, 0.3 parts of ginseng, 3 parts of rose, 0.5 parts of polygonatum, 2 parts of wolfberry, 1 part of cassia seed, and 3 parts of chrysanthemum. Add 10 times the weight of the herbs in water and reflux extract for 90 minutes. Filter and collect the filtrate and residue.

[0035] (2) Take the medicinal residue in step (1), add 8 times the volume of water by weight of the medicinal material, reflux and extract for 60 minutes, filter, and collect the filtrate.

[0036] (3) Take the medicinal residue in step (2), add 8 times the volume of water by weight of the medicinal material, reflux and extract for 60 minutes, filter, and collect the filtrate.

[0037] (4) The filtrates obtained in step (1), step (2) and step (3) were combined and concentrated under reduced pressure to obtain an extract, and 0.06 parts of phosphatidylserine and 0.03 parts of taurine were added to prepare a composition.

[0038] Example 3 A method for preparing a composition comprises the following steps:

[0039] (1) Accurately weigh 2 parts oyster, 1 part dried tangerine peel, 1.5 parts poria, 0.5 part ginseng, 0.5 part rose, 1.5 parts polygonatum, 1 part wolfberry, 1 part cassia seed, and 1 part chrysanthemum. Add 10 times the weight of the herbs in water and reflux extract for 120 minutes. Filter and collect the filtrate and residue.

[0040] (2) Take the medicinal residue in step (1), add water in an amount 6 times the weight of the medicinal material, reflux and extract for 120 minutes, filter, and collect the filtrate.

[0041] (3) Take the medicinal residue in step (2), add 8 times the volume of water by weight of the medicinal material, reflux and extract for 60 minutes, filter, and collect the filtrate.

[0042] (4) The filtrates obtained in step (1), step (2) and step (3) are combined and concentrated under reduced pressure to obtain an extract, and 0.05 parts of phosphatidylserine and 0.05 parts of taurine are added to prepare a composition.

[0043] Example 4 Experimental Study on Antidepression and Stress Improvement

[0044] 1. Experimental Materials and Drugs

[0045] 1. Drugs and Reagents

[0046] Aluminum chloride, ferrous sulfate, scopolamine hydrobromide, D-galactosidase, and huperzine A were purchased from Aladdin Reagent (Shanghai) Co., Ltd. Cholinesterase and SOD kits were purchased from Nanjing Jiancheng Bioengineering Institute.

[0047] 2. Experimental instruments

[0048] Fluoxetine was purchased from TCI (Shanghai) Chemical Industry Development Co., Ltd. Test drug: the composition prepared in Example 3 of the present invention.

[0049] 3. Experimental Animals

[0050] SPF male Kunming mice, weighing 18-22 g, were purchased from the Experimental Animal Center of Nanjing University of Chinese Medicine with the qualification certificate number SCXK (Zhe) 2008-0033.

[0051] 2. Experimental Methods

[0052] 1. Establishment of a Chronic Stress-induced Depression Mouse Model and Administration of Composition

[0053] The animals were placed for 7 days to adapt to the environment, and body weight and sugar water preference rate tests were performed, and mice with abnormal values were eliminated. Mice with normal test scores were selected and randomly divided into 6 groups, with 15 mice in each group. The groups were blank group, model group, low-dose group of the composition, medium-dose group of the composition, high-dose group of the composition, and fluoxetine group. The blank group mice were raised separately from the model mice and no stimulation was given. The model mice were randomly given two different stimuli every day, and the stimulation methods included: 24h water deprivation, 24h food deprivation, tilted cage, electric shock, 4h restraint, wet cage, and day and night reversal. Body weight and sugar water preference tests were performed every week, and the changes in mouse weight and sugar water preference rate were recorded. After 8 weeks, after the depressive phenotype appeared, the depressed mice were gavage-administered for 7 days. The animal grouping and dosage are detailed in Table 1.

[0054] Table 1 Animal groups and dosages

[0055] Animal Group Dosage and days of administration Blank group 0.9% saline, 10 days Model Group 0.9% saline, 10 days Combination low dose group 1.35 g / kg / day for 10 days Dosage group in the composition 2.70 g / kg / day for 10 days High dose group of the composition 4.05 g / kg / day for 10 days Fluoxetine group 7.2 mg / kg / day for 10 days

[0056] 2. Efficacy evaluation method

[0057] (1) Behavioral testing methods

[0058] Sugar Preference Test: This test measures changes in reward sensitivity by measuring mice's preference for sucrose and reduced sucrose intake, thereby assessing their depression. The experiment consists of a sugar acclimation phase and a test phase. During the sugar acclimation phase, mice are housed individually. On the first day, they are given two 200ml bottles of a 1% sucrose solution. After 24 hours of acclimation, one bottle of sugar solution is replaced with a 200ml bottle of pure water. On the third day, they are deprived of food and water. On the fourth day, during the formal testing phase, mice are given a 200ml bottle of 1% sucrose solution and a 200ml bottle of pure water, respectively. The weight of each bottle is recorded. Four hours later, the mice's sugar and pure water consumption is recorded. The sugar preference rate is calculated as sugar water consumption / (sugar water consumption + pure water consumption) x 100%.

[0059] Tail suspension test: Apply adhesive tape approximately 1 cm away from the mouse's tail, and suspend it on a platform with its head approximately 15 cm from the experimental table. Suspend for 6 minutes with the mouse hanging upside down. Initially, the mouse will struggle and shake, but will then give up. Use ANY-MAZE software to record the duration of immobility of the mouse for 2 to 6 minutes.

[0060] Forced swimming test: Place mice individually in a cylindrical glass tank filled with clean water, maintain the water temperature at 25°C and the water depth at about 20 cm, and force the mice to swim for 6 minutes. The hind paws of the mice cannot touch the water tank during swimming. The immobility state of the mice is recorded as the mice give up struggling and their bodies passively float on the water surface. Use ANY-MAZE software to record the duration of the mice's immobility within 2 to 6 minutes.

[0061] (2) Determination of serum stress factor levels

[0062] After behavioral testing, mice were sacrificed and blood was collected from the orbital cavity. The blood was allowed to rest for 2 hours at room temperature, then centrifuged at 3500 rpm / min at 4°C. Serum was collected and assayed for CRF, ATCH, and corticosterone levels. The assay range of the kit was 7.8–500 pM.

[0063] (3) Neurotransmitter determination

[0064] Sample processing: After completing behavioral testing, chronic stress-induced depression mice were sacrificed and whole brain tissue was obtained by dissection. A certain volume of formic acid (0.5 M) was added at a concentration of 5 g / mL, and the homogenate was prepared by high-speed dispersion. The supernatant was collected after centrifugation at 13,200 rpm for 5 minutes.

[0065] Liquid chromatography separation: Chromatographic conditions: Mobile phase: 0.1% formic acid (A), acetonitrile + 0.1% formic acid. Flow rate: 0.2 ml / min. Gradient conditions: 0.0 min: 99% A; 2.0 min: 99% A; 6.0 min: 90% A; 10 min: 90% A.

[0066] Mass spectrometry detection: Drying gas temperature: 325°C; Drying gas flow: 10 L / min; Capillary voltage (Vcap): 4000 V; Nebulizer voltage: 35 psig; Detection polarity: Positive; Scan mode: Multiple ion detection (MRM); Ion pairs detection: 154.1>137.1, 154.1>91.1 (dopamine); 170.1>153.1, 170.1>107.1 (norepinephrine); 170.1>153.1, 170.1>107.1 (norepinephrine); 177.1>160.1, 177.1>115.1 (5-hydroxytryptamine);

[0067] (4) Determination of neurotrophic factor content in hippocampal tissue

[0068] After behavioral testing, mice were sacrificed, and hippocampal tissue was dissected, rapidly frozen in liquid nitrogen, and pulverized. Appropriate tissue weight was weighed and 10 volumes of tissue lysis buffer (10 mM HEPES, pH 7.5, 1 M NaCl, 1 mM EDTA, 1 mM EGTA, 0.5% Triton X-100, 5 mM benzamidine HCl, 10 μM aprotinin, 10 μM leupeptin) were added. NGF and BDNF ELISA kits were used to measure NGF and BDNF levels according to the kit's protocol. The detection range of the kit is 7.8–500 pg / mL.

[0069] (5) Determination of pro-inflammatory substance content in the hippocampus

[0070] Samples were prepared as above. LPS, IL-1β, IL-6, and TNF-α ELISA kits were used to measure LPS, IL-1β, IL-6, and TNF-α levels according to the kit's protocol. The detection range of the kits is 7.8–500 pg / mL.

[0071] 3. Statistical processing

[0072] All experimental data were statistically processed using SPSS 18.0 statistical processing software. The results are expressed as ± s. The differences between the groups were tested using One-way ANOVA. P < 0.05 was considered statistically significant.

[0073] 3. Experimental Results

[0074] 1. Results of the Sugar Water Preference Test in Chronic Stress-Induced Depressive Mice

[0075] After 7 days of administration, the sugar water preference test of chronic stress-induced depression mice was conducted. Figure 1 It can be seen that after 7 days of oral administration, the composition provided by the present invention can improve the sugar preference index of mice, which is significantly different from that of the model group (P<0.05), showing an obvious antidepressant effect, and its trend is better than that of the positive drug fluoxetine.

[0076] 2. Results of the tail suspension test in chronic stress-induced depression mice

[0077] Seven days after administration, the chronic stress-induced depression mice were subjected to forced swimming test. Figure 2 It can be seen that after 7 days of gavage, the composition provided by the present invention can reduce the immobility time of the mice in tail suspension, which is significantly different from that of the blank group (P<0.05). Its trend is comparable to that of the positive drug fluoxetine, showing a significant antidepressant effect.

[0078] 3. Results of the forced swim test in chronic stress-induced depression mice

[0079] Seven days after administration, the chronic stress-induced depression mice were subjected to forced swimming test. Figure 3 It can be seen that after 7 days of oral administration, the composition provided by the present invention can reduce the immobility time of mice in forced swimming, which is significantly different from that of the blank group (P<0.05). The trend is comparable to that of the positive drug fluoxetine, showing a significant antidepressant effect.

[0080] 4. Effect of the composition on stress factors in the serum of chronic stress-induced depression mice

[0081] Depend on Figure 4 As can be seen, after 7 days of oral administration, both the medium and high doses of the composition provided by the present invention significantly reduced the serum levels of CRF, ACTH, and corticosterone, which are closely related to the onset of depression, compared with the model group (P < 0.05). In comparison, the effect trend is similar to that of the positive drug fluoxetine.

[0082] 5. Effects of the composition on neurotransmitters in the brains of animals with chronic stress and depression

[0083] Depend on Figure 5 As can be seen, both the medium and high doses of the composition provided by the present invention significantly increased the levels of dopamine, norepinephrine, and serotonin in the mouse brain, with significant differences compared to the blank group (P < 0.05). In comparison, the positive drug fluoxetine only significantly upregulated serotonin. The composition provided by the present invention regulates a wider range of neurotransmitter targets, potentially exerting its therapeutic effect on depression at multiple targets.

[0084] 6. Effect of the composition on neurotrophic factors in the brains of depressed animals

[0085] Depend on Figure 6 As can be seen, after seven days of oral administration, both the medium and high doses of the composition provided by the present invention significantly increased the levels of BDNF and NGF, which are closely related to the onset of depression, in the hippocampus of mice, with significant differences compared to the model group (P < 0.05). In comparison, the composition significantly enhanced the effect of NGF, with a trend stronger than fluoxetine, achieving excellent technical results.

[0086] 7. Effect of the composition on pro-inflammatory substances in the hippocampus of chronic stress-induced depression mice

[0087] Depend on Figure 7As can be seen, after seven days of oral administration, both the medium and high doses of the composition provided by the present invention significantly reduced the levels of LPS, IL-1β, IL-6, and TNF-α, which are closely associated with the pathogenesis of depression, in the hippocampus of mice, with significant differences compared to the model group (P<0.05). In contrast, fluoxetine was less effective in reducing LPS expression, suggesting that the composition has more targets for regulating neuroinflammatory factors, achieving excellent technical results.

[0088] These experimental results demonstrate that the composition provided by this invention significantly alleviates depressive-like behaviors in animals, inhibits HPA axis activation induced by stress, increases the supply of neurotransmitters and neurotrophic factors in the brain, and suppresses central nervous system inflammation. This suggests that the composition has high potential for development as a food, healthcare product, or pharmaceutical.

[0089] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A composition having the effect of improving depression and stress, characterized in that: The invention is prepared from the following raw materials in parts by weight: 1-10 parts of oyster, 0.5-5 parts of dried tangerine peel, 0.5-5 parts of poria cocos, 0.1-1 parts of ginseng, 0.2-2 parts of rose, 0.5-5 parts of polygonatum, 0.5-5 parts of wolfberry, 0.5-5 parts of cassia seed, 0.5-5 parts of chrysanthemum, 0.01-0.1 parts of phosphatidylserine and 0.01-0.1 parts of taurine.

2. The composition according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 2-5 parts of oyster, 1-4 parts of dried tangerine peel, 1-4 parts of poria, 0.2-0.5 parts of ginseng, 0.5-1.5 parts of rose, 1-4 parts of polygonatum, 1-4 parts of wolfberry, 1-4 parts of cassia seed, 1-4 parts of chrysanthemum, 0.02-0.05 parts of phosphatidylserine and 0.02-0.05 parts of taurine.

3. The composition for improving depression and stress according to claim 1, wherein: The invention is prepared from the following raw materials in parts by weight: 2 parts of oyster, 1 part of dried tangerine peel, 1.5 parts of poria, 0.4 part of ginseng, 0.5 part of rose, 1.5 parts of polygonatum, 1 part of wolfberry, 1 part of cassia seed, 1 part of chrysanthemum, 0.05 part of phosphatidylserine and 0.05 part of taurine.

4. The composition for improving depression and stress according to claim 1, wherein: The invention is prepared from the following raw materials in parts by weight: 5 parts of oyster, 1 part of dried tangerine peel, 2 parts of poria, 0.3 parts of ginseng, 1 part of rose, 2 parts of polygonatum, 3 parts of wolfberry, 2 parts of cassia seed, 2 parts of chrysanthemum, 0.02 parts of phosphatidylserine and 0.1 parts of taurine.

5. The composition for improving depression and stress according to claim 1, wherein: The invention is prepared from the following raw materials in parts by weight: 3 parts of oyster, 3 parts of dried tangerine peel, 1 part of poria, 0.5 parts of ginseng, 3 parts of rose, 0.5 parts of polygonatum, 2 parts of wolfberry, 1 part of cassia seed, 3 parts of chrysanthemum, 0.06 parts of phosphatidylserine and 0.03 parts of taurine.

6. The method for preparing the composition having the effect of improving depression and stress according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) Take oyster, tangerine peel, poria, ginseng, rose, polygonatum, wolfberry, cassia seed, and chrysanthemum by weight, add 5 to 15 times the volume of the medicinal materials, reflux extract 2 to 3 times, each time for 1 to 2 hours, filter, and combine the filtrates; (2) The filtrate of step (1) was concentrated under reduced pressure, and phosphatidylserine and taurine were added according to weight to prepare a composition.

7. Use of the composition according to any one of claims 1 to 5 having the effect of improving depression and stress in the preparation of a medicament for improving depression.

8. The use according to claim 7, characterized in that The extract of the composition is prepared with a pharmaceutically acceptable carrier into oral liquid, tablet, decoction, granule, decoction or extract.

Images