A composition for relieving depression, its preparation method and application

Abstract

The application provides a composition for relieving depression, comprising 10-17 parts of star anise, 10-15 parts of fennel, 9-12 parts of balm mint, 18-25 parts of day day flower, 8-15 parts of clove, 12-20 parts of black sesame, 12-16 parts of bergamot, 5-17 parts of hawthorn, 15-20 parts of turmeric, 5-10 parts of pumpkin, 5-10 parts of red bean, 15-20 parts of citrus fruit drop, 5-17 parts of walnut, 4-7 parts of medlar. The preparation method comprises the following steps: crushing, water distillation, physical field treatment, decocting, reduced pressure concentration, drying, embedding by using liposome, spray drying into powder and the like. The application constructs a multi-directional anti-depression formula. Compared with the health care product / medicine with single or few components in the prior art, the application can more effectively restore liver function, relieve depression symptoms, and avoid the problem of insignificant effect caused by short-acting single component, drug resistance and large side effect in the prior art.

Description

Technical Field

[0001] This invention belongs to the field of biometabolic technology, and in particular relates to a composition for relieving depression, its preparation method and application. Background Technology

[0002] Depression is the second leading cause of lost healthy life years. Currently, taking antidepressants is the primary strategy for controlling depressive episodes. However, clinical evidence suggests that the efficacy of antidepressants is not ideal; only 40% of patients experience clinical benefit after their first dose, and the effects typically appear after two weeks. Furthermore, most antidepressants only gradually take effect after about two weeks of use, and patients are prone to adverse reactions such as vomiting and suicidal tendencies for a period after starting medication.

[0003] Food-derived plant polyphenols and essential oils, among other active ingredients, possess unique advantages in the prevention and adjunctive treatment of depression. Animal and clinical studies have found that these active ingredients have significant preventive and adjunctive therapeutic effects on depression, with minimal toxic side effects. Notably, compared to chemical drugs, food-derived plant essential oils have unique advantages, including multiple targets, high pharmacological activity, easy crossing of the blood-brain barrier, and multiple routes of administration, attracting widespread attention from scholars both domestically and internationally.

[0004] Although polyphenols have significant potential in alleviating depression, many polyphenols are often large and have complex structures, making it difficult for them to cross the intestinal wall and enter the bloodstream. Furthermore, they have low solubility in water. Their low water solubility and complex structure limit their absorption, resulting in low bioavailability. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a composition for relieving depression, its preparation method and application.

[0006] To address the aforementioned technical problems, the present invention provides a composition for relieving depression, comprising: 10-17 parts star anise, 10-15 parts fennel, 9-12 parts lemon balm, 18-25 parts bitter orange blossom, 8-15 parts clove, 12-20 parts black sesame, 12-16 parts Buddha's hand, 5-17 parts hawthorn, 15-20 parts turmeric, 5-10 parts pumpkin, 5-10 parts red bean, 15-20 parts fallen citrus fruit, 5-17 parts walnut, and 4-7 parts goji berries.

[0007] The above-mentioned composition further includes: 13 parts star anise, 12 parts fennel, 10 parts lemon balm, 20 parts bitter orange blossom, 11 parts clove, 12 parts black sesame, 15 parts Buddha's hand, 7 parts hawthorn, 15-20 parts turmeric, 6 parts pumpkin, 6 parts red bean, 16 parts citrus fruit, 9 parts walnut, and 4 parts goji berries.

[0008] The above-described composition further includes essential oils and polyphenol extracts, said essential oils and polyphenol extracts being obtained from raw materials including: 10-17 parts star anise, 10-15 parts fennel, 9-12 parts lemon balm, 18-25 parts bitter orange blossom, 8-15 parts clove, 12-20 parts black sesame, 12-16 parts bergamot, 5-17 parts hawthorn, 15-20 parts turmeric, 5-10 parts pumpkin, 5-10 parts red bean, 15-20 parts citrus fruit, 5-17 parts walnut, and 4-7 parts goji berries.

[0009] Based on a general technical concept, the present invention also provides a method for preparing the composition, the method comprising:

[0010] S1, star anise, fennel, lemon balm, bitter orange blossom, clove, black sesame, Buddha's hand, hawthorn, turmeric, pumpkin, red bean, citrus fallen fruit, walnut and goji berry are crushed to obtain material 1;

[0011] S2. The material 1 is subjected to water distillation to obtain essential oil and material 2;

[0012] S3. Mix the material 2 with ethanol, perform physical field treatment, then decoct, concentrate the filtrate obtained by decompression and dry to obtain polyphenol extract.

[0013] S4. The essential oil and the polyphenol extract are mixed, encapsulated in liposomes, and spray-dried into powder.

[0014] In the above preparation method, further, in step S2, the mass ratio of material 1 to water is 1:1 to 6, and the water distillation time is 2 to 5 hours.

[0015] The above-described preparation method further includes, in step S3, the physical field treatment comprising one or more of ultrasonic treatment, microwave treatment, and ultra-high pressure treatment;

[0016] The ultrasonic treatment power is 20–100 kHz, the temperature is 30–90℃, and the treatment time is 10 s–2 h.

[0017] The microwave processing power is 50–500 W, the temperature is 30–90℃, and the processing time is 10 s–2 h.

[0018] The ultra-high pressure treatment intensity is 50–800 MPa, the temperature is 30–90℃, and the treatment time is 10s–2h.

[0019] In the above preparation method, in step S3, material 2 is mixed with ethanol at a mass ratio of 1:3 to 10; the concentration of ethanol is 30% to 90%.

[0020] In the above preparation method, the decoction time in S3 is 2-4 hours, the extraction is performed 1-3 times, the concentration under reduced pressure is 30-60℃, and the drying temperature is -40℃ to 80℃.

[0021] In the above preparation method, further, in step S4, the essential oil and polyphenol extract are mixed in a vortex mixer for 10s to 5min, and the mixture of essential oil and polyphenol is encapsulated by inclusion technology, nanotechnology and / or microencapsulation technology to prepare particles with a particle size of about 150 to 500 nm.

[0022] Based on a general technical concept, the present invention also provides the use of the described composition in the preparation of a medicament for treating depression by modulating the liver-brain axis.

[0023] Compared with the prior art, the advantages of the present invention are as follows:

[0024] (1) This invention provides a composition for relieving depression. By combining various food-derived antidepressants (such as lemon balm, turmeric, bitter orange blossom, bergamot, etc.), a multi-faceted antidepressant formula is constructed. Compared with existing health products / drugs containing only one or a few ingredients, this invention can more effectively restore liver function and relieve depressive symptoms, avoiding the problem of insignificant effects caused by the short duration of action of a single ingredient in existing products. All the compositions of this invention are food-derived substances and have no significant toxic effects on the body.

[0025] (2) This invention provides a composition for relieving depression, which uses a green extraction method to separate the effective antidepressant components (essential oil and polyphenols) of the composition. Compared with the composition, the essential oil and polyphenols of any composition have better antidepressant effects; because polyphenols have low water solubility, they have low bioavailability and poor biological effects. Essential oils are fat-soluble, which helps polyphenols dissolve and are absorbed after entering the digestive tract, thus improving their bioavailability. The combined use of essential oils and polyphenols in the composition further enhances the antidepressant effect. The mechanism is that the essential oils and polyphenols in the composition jointly regulate liver metabolites. Liver metabolites are transported through the blood and cross the blood-brain barrier to enter the brain, affecting the brain's synthesis of neurotransmitters, thereby relieving depressive symptoms.

[0026] (3) The present invention provides a method for preparing a composition for relieving depression. It adopts inclusion technology, nanotechnology and microencapsulation technology, which significantly improves the absorption rate and stability of essential oils and polyphenols, solves the problems of unstable essential oils and low bioavailability of essential oils and polyphenols, ensures that the product effect is more lasting and stable, significantly improves the neuroprotective effect, and overcomes the shortcomings of traditional products.

[0027] (4) This invention provides the application of a composition for alleviating depression in the preparation of a medicament for treating depression by modulating the liver-brain axis. The liver-brain axis refers to the interaction and communication network between the liver and the brain, which affects the nervous system, mood, and behavior through various mechanisms. The liver is an important metabolic organ and also participates in the synthesis of precursors for neurotransmitters, such as tryptophan and tyrosine, which are the basis for the synthesis of important neurotransmitters (such as serotonin and dopamine). Decreased liver function may lead to a reduction in the synthesis of these precursors, thereby affecting the level of neurotransmitters and leading to depressive symptoms. In patients with depression, the inflammatory response is considered an important pathophysiological mechanism. The liver participates in the inflammatory response by producing cytokines, chemokines, etc., which can affect brain function through blood circulation, thereby affecting mood and behavior. Liver dysfunction may lead to increased permeability of the blood-brain barrier, making it easier for certain harmful substances or inflammatory factors to enter the brain, affecting nerve function and leading to mood disorders. The composition of this invention may help alleviate depressive symptoms and improve the quality of life of patients by improving liver health (such as dietary improvement, drug intervention, exercise, etc.). This provides a theoretical basis for the regulation of the liver-brain axis as a new strategy for the treatment of depression. Attached Figure Description

[0028] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0029] Figure 1 The figures show the animal behavior experiment results of Experiment 1 of this invention. Figure A represents the results of the forced swimming experiment; Figure B represents the results of the tail suspension experiment; and Figure C represents the results of the sucrose preference rate experiment.

[0030] Figure 2 The results show the serum TG and LDL-C levels in mice during Experiment 2 of this invention.

[0031] Figure 3 The image shows a liver lipid metabolism thermogram of the composition and its essential oil + polyphenol group in Experiment 3 of this invention.

[0032] Figure 4 The results show that the composition and its essential oil + polyphenol group in Experiment 3 of this invention regulated the liver-brain axis.

[0033] Figure 5 This is a schematic diagram illustrating how the composition and its essential oil + polyphenol group in Experiment 3 of this invention regulate the liver-brain axis through lipid metabolism pathways. Detailed Implementation

[0034] The present invention will be further described below with reference to specific preferred embodiments, but this does not limit the scope of protection of the present invention.

[0035] The materials, reagents, and instruments used in the following examples are all commercially available. Unless otherwise specified, the experimental methods used in the following examples are conventional methods in the art. All units of "parts" in the following examples refer to parts by mass.

[0036] Example 1

[0037] A composition for relieving depression includes: 13 parts star anise, 12 parts fennel, 10 parts lemon balm, 20 parts bitter orange blossom, 11 parts cloves, 12 parts black sesame seeds, 15 parts Buddha's hand, 7 parts hawthorn, 17 parts turmeric, 6 parts pumpkin, 6 parts red beans, 16 parts citrus fruit, 9 parts walnuts, and 4 parts goji berries.

[0038] The preparation method includes the following steps: preparing the above composition, drying it to a moisture content of <3.0%, and pulverizing it into powder.

[0039] Example 2

[0040] A composition for relieving depression includes: 13 parts star anise, 12 parts fennel, 10 parts lemon balm, 20 parts bitter orange blossom, 11 parts cloves, 12 parts black sesame seeds, 15 parts Buddha's hand, 7 parts hawthorn, 17 parts turmeric, 6 parts pumpkin, 6 parts red beans, 16 parts citrus fruit, 9 parts walnuts, and 4 parts goji berries.

[0041] Its preparation method includes the following steps:

[0042] (1) The star anise, fennel, lemon balm, bitter orange blossom, clove, black sesame, Buddha's hand, hawthorn, turmeric, pumpkin, red bean, citrus fruit, walnut and wolfberry in the above composition are dried to a moisture content of <3.0%, pulverized and mixed in proportion to obtain material 1;

[0043] (2) After water distillation of material 1, essential oil is obtained. The remaining material is collected and named material 2.

[0044] (3) Mix material 2 with 9 times the mass of 65% (mass percentage) ethanol, treat with ultrasound at 400 MPa for 20 min, then extract polyphenols at 80℃, extract twice, each time for 3 h, concentrate the filtrate under reduced pressure at 40℃, and freeze dry to obtain polyphenol extract.

[0045] (4) Mix the essential oil and polyphenols by vortexing for 2 min, encapsulate the composition with liposomes, and spray dry into powder.

[0046] Comparative Example 1

[0047] A composition for relieving depression includes: 22 parts bitter orange blossom, 13 parts black sesame, 18 parts turmeric, 5 parts red bean, and 4 parts goji berries, prepared as a powder.

[0048] Comparative Example 2

[0049] A composition for relieving depression includes: 13 parts star anise, 12 parts fennel, 10 parts lemon balm, 20 parts bitter orange blossom, 11 parts cloves, 12 parts black sesame seeds, 15 parts Buddha's hand, 7 parts hawthorn, 11 parts turmeric, 6 parts pumpkin, 6 parts red beans, 16 parts citrus fruit, 9 parts walnuts, and 4 parts goji berries.

[0050] The preparation method includes the following steps: adding 5 times the mass of water to the mixture, distilling the essential oil over water, encapsulating it with liposomes, and spray drying it into powder.

[0051] Comparative Example 3

[0052] A composition for relieving depression includes: 13 parts star anise, 12 parts fennel, 10 parts lemon balm, 20 parts bitter orange blossom, 11 parts cloves, 12 parts black sesame seeds, 15 parts Buddha's hand, 7 parts hawthorn, 11 parts turmeric, 6 parts pumpkin, 6 parts red beans, 16 parts citrus fruit, 9 parts walnuts, and 4 parts goji berries.

[0053] The preparation method includes the following steps: the mixture is mixed with 9 times its mass of 65% ethanol, ultrasonically treated at 400 MPa for 20 min, and then the polyphenols are extracted at 80℃. The extraction is repeated twice, each time for 3 h. The filtrate is concentrated under reduced pressure at 40℃, and then freeze-dried to obtain the polyphenol extract. The extract is then encapsulated in liposomes and spray-dried into powder.

[0054] Experiment 1: To investigate the effect on alleviating depressive symptoms in animals.

[0055] Experimental methods:

[0056] 1. Grouping: Male C57BL / 6 mice (3 weeks old, 8 mice per cage) were housed for one week under standard conditions (humidity: 40%~60%, temperature: 20~25℃, 12 / 12 h light / dark cycle) with free food and water. Based on body weight, the mice were divided into: a blank control group (physiological saline, ig), an animal chronic unpredictable stress (CUMS) model group (physiological saline, ig), a fluoxetine group (10 mg / kg, ig), and the treatment group of Example 2 (100 mg / kg, ig), etc. Administered by gavage once daily for four consecutive weeks.

[0057] 2. Establishment of the Depression Model: During the experiment, control mice were placed alone in an undisturbed environment with no intervention other than routine care (such as cage cleaning). Other mice were placed in separate cages (one mouse per cage) and subjected to 7 weeks of chronic, unpredictable stress. Daily stressors included: restraint for 4 h; wet mat for 24 h; fasting for 24 h; dehydration for 24 h; tail suspension for 2 min; forced swimming for 5 min; reversal of the light / dark cycle; cage tilt (45°) for 24 h; cold stimulation for 1 h (4°C); foot stimulation for 1 min; stroboscopic stimulation for 12 h; and crowded housing for 24 h. Twelve stimuli were randomly administered, two per day. All stimuli were administered in a random order at different times, with different stimuli provided on consecutive days.

[0058] 3. Depressive behavioral assessment:

[0059] 3.1 Sucrose Preference Test: The sucrose preference experiment consisted of two parts: adaptation training and testing. During the training process, two bottles of 1% (w / v) sucrose solution were placed in each cage for the first 24 hours, and one of the bottles was replaced with pure water for the next 24 hours. After 18 hours of food and water removal, one bottle of 1% (w / w) sucrose solution and one bottle of aqueous solution were placed in each cage for the next 25 hours. Each bottle was weighed before and after the test, and the total liquid consumption, sucrose consumption, and pure water consumption were recorded. The formula for the sucrose preference index is as follows: Sucrose preference (%) = Sucrose water consumption / (Sucrose water consumption + Pure water consumption).

[0060] 3.2 Forced Swimming Test: Mice were individually placed in a cylindrical acrylic container (45 cm high, 10 cm in diameter) at a water depth of 30 cm and a temperature of 25 ± 1.0℃. The total swimming time for each mouse was recorded as 6 minutes. After a 1-minute acclimatization period, the duration of stillness was measured during the final 5 minutes. The water was changed immediately after each test to prevent odor interference, and the mice were separated by partitions to avoid mutual interference.

[0061] 3.3 Tail Suspension Test: Mice were suspended 60 cm above the ground for 6 minutes, with a fixation tape placed 1 cm from the tip of the tail. Real-time video recording was used to record the process. The duration of immobility in the last 5 minutes was calculated and analyzed. Mice tested simultaneously were separated by partitions to reduce mutual interference. After each test, the area around the equipment was cleaned with 75% ethanol, and the equipment itself was wiped down to eliminate any influence from feces and avoid odor interference.

[0062] 4. Experimental Results:

[0063] Figure 1The results of the animal behavior experiment in Experiment 1 of this invention are shown. A in the figure represents the results of the forced swimming experiment. In the forced swimming experiment, the mice in the Example 2 group showed the best antidepressant effect, which was significantly higher than that in the Comparative Example 1 and Comparative Example 3 groups. This indicates that the Example 2 group effectively alleviated the depressive state of the mice.

[0064] Figure B shows the results of the tail suspension experiment. In the tail suspension experiment, the mice in the Example 2 group struggled for a much longer time than all the comparative groups, demonstrating its strong antidepressant effect.

[0065] Figure C represents the results of the sucrose preference rate experiment. Regarding the sucrose preference rate, the preference rate in Example 2 group was 60%, demonstrating a strong preference for sweetness, while in Comparative Example 1 group it was only 35%. This further confirms that the combination of essential oils and polyphenols in the composition can effectively enhance the mice's sense of pleasure and reduce their level of depression.

[0066] In summary, chronic unpredictable stress led to a decrease in sucrose consumption in mice, an increase in the duration of immobility 4 minutes after the tail suspension test, and an increase in the duration of immobility during swimming, all of which were significantly different from the control group (P < 0.05). However, after intervention with the composition of Example 2, the sucrose consumption rate increased, the duration of immobility 4 minutes after the tail suspension test and the duration of immobility during swimming decreased, all of which were significantly different from the model group (P < 0.05), but not significantly different from the control group, and the effect was equivalent to that of the fluoxetine positive control group. This indicates that after intervention with the composition and its components of Example 2, the duration of despair in mice was significantly reduced, anhedonia was alleviated, and behavioral performance tended to normalize, meaning that depressive-like behavior in mice was significantly improved.

[0067] To investigate the effects of different components in the composition of Example 2 on alleviating depressive symptoms in animals, the following compositions were further examined:

[0068] Composition 1: Citrus aurantium.

[0069] Composition 2: Buddha's Hand.

[0070] Composition 3: Black sesame seeds.

[0071] Composition 4: Citrus fruit drop.

[0072] Composition 5: Turmeric.

[0073] Composition 6: 20 parts bitter orange blossom, 15 parts Buddha's hand, 12 parts black sesame, 16 parts fallen citrus fruit, and 17 parts turmeric.

[0074] Composition 7: 13 parts star anise, 12 parts fennel, 10 parts lemon balm, 11 parts cloves, 7 parts hawthorn, 6 parts pumpkin, 6 parts red beans, 9 parts walnuts, and 4 parts goji berries.

[0075] The essential oils and polyphenol extracts of the above-mentioned groups were prepared according to the preparation method of Example 2. The essential oils and polyphenols were vortexed for 2 min to mix them. The compositions were then encapsulated in liposomes and spray-dried into powder. The effects of different components on alleviating depressive symptoms in animals were investigated, and the results are listed in Table 1.

[0076] Table 1: Effects of different components on alleviating depressive symptoms in animals

[0077]

[0078] The results in Table 1 show that, compared with the depression model group, bitter orange blossom, Buddha's hand, black sesame, citrus fruit drop, turmeric, and their combinations all have significant antidepressant effects. Among them, Example 2 has the best antidepressant effect, with the shortest tail immobility time and forced swimming immobility time, as well as the highest sucrose preference rate. However, Composition 7 has no significant antidepressant effect. Therefore, it is believed that bitter orange blossom, Buddha's hand, black sesame, citrus fruit drop, and turmeric are important components in the composition for relieving depression. The volatile components (such as linalool) and polyphenols (such as naringin) in bitter orange extract produce antidepressant effects by regulating neurotransmitters; the curcumin and other polyphenols in turmeric can affect neurotransmitters in the brain, thus potentially influencing mood regulation; it has the effect of relieving depressive symptoms; bergamot has the effect of soothing the liver and regulating qi, and can alleviate symptoms such as liver qi stagnation and chest tightness; the polyphenols in bergamot can regulate liver function and promote blood circulation, thereby achieving the effect of soothing the liver and relieving depression; black sesame seeds are rich in unsaturated fatty acids (omega-3 and omega-6), which may affect the synthesis, release, and reuptake of serotonin, dopamine, and norepinephrine, which play a key role in relieving depression and other mood regulation; citrus fruit drop is rich in polyphenols, has good anti-inflammatory function, helps resist the deterioration of the nervous system caused by the breakdown of nerve cells, protects nerves from damage, and helps promote brain function. This combination of five substances (composition 6) is used in the essential oil.

[0079] The antidepressant effect of polyphenols is stronger than that of single substances (compositions 1-5). The compositions alleviate depressive symptoms by regulating the liver-brain axis and regulating the level of neurotransmitters in the brain.

[0080] However, polyphenols have low bioavailability, and effective delivery methods need to be found to achieve optimal results. Star anise, fennel, lemon balm, cloves, hawthorn, pumpkin, red beans, walnuts, and goji berries are rich in volatile oils, vitamins, and minerals, and when combined with bitter orange blossom, Buddha's hand, black sesame, citrus fruit drop, and turmeric, they can further enhance their antidepressant effects.

[0081] Therefore, the composition provided by the present invention achieves an antidepressant effect through the synergistic effect of its components.

[0082] Experiment 2: Examining the level of neurotransmitters in the brain.

[0083] Brain and liver samples were collected from mice in the examples and comparative studies for ELISA detection. Brain 5-HT and DA levels, and liver IL-1β, IL-6, AST, and ALT concentrations were detected using ELISA kits, with all experimental procedures strictly following the manufacturer's instructions. Furthermore, serum TG and LDL-C levels were analyzed using a fully automated biochemical analyzer. Table 2 shows the detection results of brain and liver biochemical indicators.

[0084] Table 2: Results of Biochemical Indicators in Brain and Liver

[0085]

[0086] The results in Table 2 show that the levels of 5-HT (serotonin) and DA (dopamine) measured in brain tissue significantly increased neurotransmitter levels in all groups. Specifically, the levels of 5-HT and DA in Example 2 were significantly higher than in the other groups, while the neurotransmitter levels in Comparative Example 1 were the lowest. The combined use of essential oils and polyphenols in the composition to increase 5-HT and DA levels suggests that they may improve the mood of mice by synergistically regulating the balance of neurotransmitters, exhibiting a good depressive-relieving effect.

[0087] Regarding inflammatory factors, all groups significantly reduced the concentrations of the liver inflammatory factors IL-1β and IL-6, indicating that the various formulations and components (essential oils and polyphenols) of the composition can effectively alleviate liver inflammation. Specifically, the concentrations of IL-1β and IL-6 in the liver of mice in Example 2 were significantly lower than in other groups, suggesting that Example 2 may have a significant inhibitory effect on the inflammatory response in the liver. Regarding liver function indicators, the levels of AST and ALT in Example 2 were lower than in Control Group 1, further confirming the effect of Example 2 in protecting liver function.

[0088] Figure 2 The results showed serum TG and LDL-C levels in mice. Low serum TG and LDL-C levels help reduce the burden on multiple organs, including the brain and liver. The results indicated that all groups significantly reduced serum TG and LDL-C levels, demonstrating that the various formulations and components (essential oils and polyphenols) of the composition can effectively lower blood lipid levels. Specifically, the TG levels in Example 2 and Comparative Example 2 were lower, the LDL-C level in Example 2 was the lowest, and the TG and LDL-C levels in Comparative Example 1 were the highest. The combination of serum lipid results and the antidepressant effect of Example 2 may suggest that the antidepressant effect of Example 2 may be related to its potential metabolic protective effect.

[0089] Experiment 3: Investigating lipid metabolism.

[0090] 100 μL of liver and brain homogenate were collected from mice in the examples and comparative examples, and mixed with 80 μL of methanol and 400 μL of methyl tert-butyl ether. The mixture was centrifuged at 15,000 rpm for 15 min at 4 °C. Subsequently, 350 μL of the supernatant was transferred to a 1.5 mL EP tube, dried under nitrogen, and 100 μL of extract (isopropanol:acetonitrile = 1:1) was added. The mixture was vortexed and mixed for 30 s, followed by low-temperature sonication for 5 min. The mixture was then centrifuged at 15,000 rpm at 4 °C. The supernatant was collected and analyzed using LC-MS. Since the composition and its components have a significant protective effect against chronic unpredictable liver damage and can reduce blood lipids, we examined liver and brain lipid metabolism in the Example 1 group (CG), Example 2 group (OP), and depression group (CUMS), comparing the metabolites of the three groups to verify that the composition and its components alleviate depressive symptoms by regulating the liver-brain axis.

[0091] Figure 3 Liver lipid metabolism thermograms of the composition of Example 1 and the essential oil + polyphenol group in Example 2. Figure 4 The results of regulating the liver-brain axis via lipid metabolism pathways were obtained from the composition of Example 1 and the essential oil + polyphenol group in Example 2. The results showed that the livers of both Example 1 and Example 2 groups exhibited significantly altered phospholipid metabolism pathways, including increased levels of diglycerides (16:2e / 18:1; 18:3e / 20:1), various triglycerides, various phosphatidylethanolamines, phosphatidylcholine (9:0 / 23:0), and phosphatidylethanolamine (16:0p / 18:1; 20:2e / 22:6; 22:4 / 22:6), and decreased levels of lysophosphatidylethanolamine (19:0; 20:0) and lysophosphatidylcholine. Significant changes were observed in the brain phospholipid metabolism pathway, with increased levels of phosphatidylethanolamine (14:0e / 16:0; 18:2 / 22:6; 8:1e / 10:0) and decreased levels of phosphatidylethanolamine (30:0 / 20:0; 4:0 / 16:1; 20:3p / 24:0), while levels of lysophosphatidylcholine (18:2; 16:1) and lysophosphatidylethanolamine (18:1; 16:1e) increased. Therefore, it is speculated that the increased phosphatidylcholine and phosphatidylethanolamine from the liver are transported to the brain via the bloodstream, where they are broken down into lysophosphatidylcholine and lysophosphatidylethanolamine, exerting an antidepressant effect. This indicates that the composition and its essential oils, in combination with polyphenols, alleviate depressive symptoms by regulating the liver-brain axis and modulating neurotransmitter levels in the brain. Figure 5 This is a schematic diagram illustrating how the composition and its essential oil + polyphenol group regulate the liver-brain axis through lipid metabolism pathways.

[0092] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make many possible variations and modifications to the technical solutions of the present invention using the methods and techniques disclosed above, or modify them into equivalent embodiments with equivalent changes, without departing from the spirit and technical essence of the present invention. Therefore, any simple modifications, equivalent substitutions, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solutions of the present invention shall still fall within the protection scope of the technical solutions of the present invention.

Claims

1. A preparation method of a composition for relieving depression, characterized in that, the composition is prepared from the following components: 10-17 parts of star anise, 10-15 parts of fennel, 9-12 parts of balm mint, 18-25 parts of day day flower, 8-15 parts of clove, 12-20 parts of black sesame, 12-16 parts of bergamot, 5-17 parts of hawthorn, 15-20 parts of turmeric, 5-10 parts of pumpkin, 5-10 parts of red bean, 15-20 parts of citrus fruit, 5-17 parts of walnut, 4-7 parts of medlar; the preparation method comprises the following steps: S1, grinding star anise, fennel, balm mint, day day flower, clove, black sesame, bergamot, hawthorn, turmeric, pumpkin, red bean, citrus fruit, walnut and medlar to obtain material 1; S2, performing water distillation on the material 1 to obtain essential oil and residual material; S3, mixing the residual material with ethanol, performing ultrasonic treatment, then extracting, and performing vacuum concentration and drying on the obtained filtrate to obtain polyphenol extract; S4, mixing the essential oil and the polyphenol extract, embedding with liposome, and spray drying into powder. The composition is prepared from the following components: 13 parts of star anise, 12 parts of fennel, 10 parts of balm mint, 20 parts of day day flower, 11 parts of clove, 12 parts of black sesame, 15 parts of bergamot, 7 parts of hawthorn, 17 parts of turmeric, 6 parts of pumpkin, 6 parts of red bean, 16 parts of citrus fruit, 9 parts of walnut, and 4 parts of medlar. In the S2, the mass ratio of the material 1 to water is 1:1-6, and the water distillation time is 2-5 h. In the S3, the ultrasonic treatment frequency is 20-100 kHz, and the temperature is 30-90℃; the treatment time is 10 s-2 h. In the S3, the residual material and ethanol are mixed according to a mass ratio of 1:3-10; the concentration of ethanol is 30%-90%. The composition is prepared by the preparation method in any one of claims 1-5.

7. Use of the composition in claim 6 in the preparation of a medicine for relieving depression.

2. The production method according to claim 1, characterized by, ​ 3. The production method according to claim 1, characterized by, ​ 4. The production method according to claim 1, characterized by, ​ 5. The method of claim 1, wherein, ​ 6. A composition for alleviating depression, characterized by comprising: ​ ​

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