A composition for soothing liver and relieving depression, tranquilizing heart and calming mind and a preparation method thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine, in particular to a composition for soothing liver and relieving depression, calming the heart and tranquilizing the mind and a preparation method thereof. The composition comprises lily, mint, gardenia and spina date seed. The composition provided by the present application has unique pharmacological effects, and can synergistically exert the effects of soothing liver and relieving depression, calming the heart and tranquilizing the mind, etc. Lily, mint, gardenia and spina date seed are all medicinal and edible herbs. Since they have mild effects and high safety, they can reduce the incidence of adverse reactions while reducing the degree of depression, thus providing a safe and effective optimization scheme for clinical use.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a composition for soothing the liver and relieving depression, calming the mind and tranquilizing the nerves, and a preparation method thereof. Background Art

[0002] Depression is a common mental disorder characterized by significant and persistent low mood. Specifically, it is manifested as loss of interest, slow thinking, decreased volitional activity, sleep disorder, appetite change, physical fatigue and suicidal tendency, accompanied by abnormalities in cognition, behavior and physiological functions. Due to its high incidence, disability rate and fatality rate, it seriously threatens human life and health.

[0003] In traditional Chinese medicine theory, depression mostly belongs to the category of depressive syndrome, and is closely related to stagnation of liver qi, disharmony of qi and blood, and emotional discomfort. The treatment of depression in traditional Chinese medicine takes overall syndrome differentiation as the core, and restores the balance of the body by soothing the liver and relieving depression, regulating qi and blood, with the advantages of multi-target regulation and individualized treatment. At the same time, it has fewer side effects and high safety, is suitable for long-term conditioning, and synergistically improves symptoms from the aspects of emotion and constitution, especially has significant effects on mild to moderate depression, drug intolerance and prevention of recurrence. Therefore, the treatment of depression with traditional Chinese medicine has become the research direction of many scholars. Summary of the Invention

[0004] In order to solve the above problems, the present invention provides a composition for soothing the liver and relieving depression, calming the mind and tranquilizing the nerves, and a preparation method thereof. The composition provided by the present invention has mild action and high safety, can reduce the incidence of adverse reactions while reducing the degree of depression, and provides a safe and effective optimization plan for clinical practice.

[0005] In order to achieve the above object, the present invention provides the following technical solutions: The present invention provides a composition for soothing the liver and relieving depression, calming the mind and tranquilizing the nerves, which is prepared from the following components in parts by weight: 15 g of lily, 10 g of mint, 10 g of gardenia, and 10 g of wild jujube seed.

[0006] The present invention also provides a preparation method of the composition according to the above technical solution, comprising the following steps: 1) Mix the lily, mint, gardenia, wild jujube seed and water, and soak to obtain a soaked material; 2) Decoct the soaked material obtained in step 1), and dry the obtained decoction to obtain the composition.

[0007] Preferably, the mass ratio of the total mass of the four components of lily, mint, gardenia and wild jujube seed to the mass of water in step 1) is 1:10.

[0008] Preferably, the soaking time in step 1) is 2 h.

[0009] Preferably, the conditions for step 2) of decocting include: decocting twice, for 30 minutes each time.

[0010] Preferably, the drying conditions in step 2) include: combining the decoctions obtained from two decoctions and filtering them; removing most of the water from the filtrate using a rotary evaporator; and drying in an 80°C oven until it is dried into powder.

[0011] Sour jujube seed, sweet, sour, and neutral in nature, enters the liver, gallbladder, and heart meridians. It nourishes the heart and liver, calms the mind and soothes the nerves, and also nourishes the liver to help soothe it, making it the principal herb. It primarily calms the mind and soothes the nerves, while also nourishing liver blood to relieve liver stagnation. Peppermint, pungent and cool, enters the liver and lung meridians. It specifically enters the liver meridian to relieve liver stagnation, clear the head and eyes, and alleviate chest tightness and irritability caused by liver stagnation. It assists the principal herb in soothing the liver and enhances its stagnation-relieving effect; its pungent and dispersing nature prevents sour jujube seed from being too cloying and hindering qi flow. Gardenia, bitter and cold, enters the heart, liver, and triple burner meridians. It clears liver stagnation and transforms into fire, purging fire and relieving irritability. It assists the principal herb in clearing heart and liver fire, preventing heat from disturbing the mind. Combined with peppermint, it achieves liver soothing, heat clearing, and also calms the mind. Both are assistant herbs. Lily bulb, sweet and slightly cold in nature, enters the heart and lung meridians. It nourishes yin and moistens the lungs, clears the heart and calms the mind. It can both nourish yin to supplement the heart-nourishing effect of jujube seed and clear the heart and relieve irritability, assisting in calming the mind. Its sweet and moistening nature balances the bitter and cold nature of gardenia, serving as an adjuvant. Peppermint, light and ascending, guides all the herbs to the liver and heart meridians. Its pungent and dispersing nature balances the nourishing and cloying nature of jujube seed and lily bulb, also serving as a guiding herb. Jujube seed nourishes the heart and calms the mind as the core, peppermint soothes the liver and relieves depression, gardenia clears liver fire, and lily bulb nourishes yin and clears the heart. The whole formula works together to soothe the liver and relieve depression, clear stagnant fire, and calm the mind.

[0012] The beneficial effects of this invention are: The composition provided by this invention exerts an antidepressant effect by inhibiting apoptosis of somatic neurons in the mouse hippocampus, alleviating hippocampal tissue damage, and thereby improving depressive-like behaviors such as behavioral despair, lack of motivation, and anhedonia. Specific effects are demonstrated in the following examples. Lily, peppermint, gardenia, and jujube seed are all medicinal and edible herbs. Due to their mild effects and high safety, they can reduce the severity of depression while lowering the incidence of adverse reactions, providing a safe and effective optimized solution for clinical practice. Attached Figure Description

[0013] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0014] Figure 1 Morphological and weight changes in mice. (A) Morphological changes in mice; (B) Weight changes in mice during the experiment.

[0015] Figure 2 Effects of the composition on behavioral despair in depressed mice. (A) Hanger rating; (B) Hanger escape latency.

[0016] Figure 3 Effects of the composition on the initiative and motivation of depressed mice. (A) Nesting behavior of the four groups of mice; (B) Nesting quality score of mice.

[0017] Figure 4 Effect of the composition on sucrose preference in depressed mice. (A) Total consumption of sucrose solution and pure water; (B) Sucrose preference index.

[0018] Figure 5 The composition can alleviate neuronal damage in the CA1 region of the hippocampus in depressed mice. (A) Representative histological examination of brain tissue in each group was performed by HE staining under a 400x magnified optical microscope (scale bar = 20 μm); the number of mature neurons under 400x magnification (scale bar = 20 μm) was detected by the NEUN method; the number of mature astrocytes under 400x magnification (scale bar = 20 μm) was detected by the GFAP method; (B) NEUN-positive cells were counted under 5 random HPFs, and then the number of positively stained cells in each group was counted and analyzed separately; (C) GFAP-positive cells were counted under 5 random HPFs, and then the number of positively stained cells in each group was counted and analyzed separately. Detailed Implementation

[0019] This invention provides a composition for soothing the liver, relieving depression, calming the mind, and soothing the nerves, prepared from the following components in parts by weight: 15g lily bulb, 10g mint, 10g gardenia fruit, and 10g jujube seed. This invention does not specify the source of the lily bulb, mint, gardenia fruit, and jujube seed; conventional commercially available products are acceptable.

[0020] The present invention also provides a method for preparing the composition described in the above technical solution, comprising the following steps: 1) Soak the lily bulbs, mint, gardenia, jujube seeds, and water to obtain the soaking material; 2) Boil the soaking material obtained in step 1), and dry the resulting decoction to obtain the composition.

[0021] This invention involves soaking a mixture of lily bulbs, mint, gardenia, jujube seeds, and water to obtain a soaking solution. In this invention, the preferred mass ratio of the four components (lily bulbs, mint, gardenia, and jujube seeds) to water is 1:10. The preferred soaking time is 2 hours.

[0022] This invention involves decocting the obtained soaking material, drying the resulting decoction, and obtaining a composition. Preferably, the decoction conditions include: decocting twice, 30 minutes each time. Preferably, the drying conditions include: combining the decoctions obtained from the two decoctions, filtering, removing most of the water from the filtrate using a rotary evaporator, and drying in an 80°C oven until it becomes powder.

[0023] This invention also provides the application of the composition described above in the preparation of a medicine for soothing the liver, relieving depression, calming the mind, and soothing the nerves. In this invention, the composition preferably has a prolonged escape latency period. In this invention, the composition preferably has a reduced sugar water preference rate. In this invention, the composition preferably alleviates hippocampal tissue damage. In this invention, the dosage form of the medicine is preferably a decoction, granules, pills, or capsules. This invention does not impose any particular limitation on the preparation method of the above-mentioned decoction, granules, pills, or capsules; conventional preparation methods are acceptable.

[0024] To further illustrate the present invention, the following detailed description is provided in conjunction with embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0025] Example 1 A method for preparing a composition that soothes the liver, relieves depression, calms the mind, and soothes the nerves includes the following steps: 1) Mix 15g of lily bulbs, 10g of mint, 10g of gardenia, and 10g of jujube seed with water at a ratio of 1:10 and soak for 2 hours to obtain the soaking material; 2) Boil the soaking material obtained in step 1), dry the resulting decoction, and obtain the composition; wherein, the decoction is performed twice, each time for 30 minutes; combine the decoctions obtained from the two decoctions and filter them, remove most of the water from the filtrate using a rotary evaporator, and dry it in an 80°C oven until it is dried into powder.

[0026] Example of drug efficacy Preparation of experimental drugs: Example 1 The prepared composition (lily, peppermint, gardenia, and jujube seed) powder was mixed with purified water to prepare a solution with a concentration of 50 mg / mL; vitamin E (VE) was mixed with purified water to prepare a solution with a concentration of 10 mg / mL; and D-galactose was mixed with purified water to prepare a solution with a concentration of 50 mg / mL.

[0027] Establishment, grouping, and administration of animal models Forty healthy male Balb / c mice (SPF grade, 20g, 7-8 weeks old) were selected and randomly divided into two groups: a control group and a model group. The model group received a subcutaneous injection of 0.2 mL of D-galactose solution in the neck and back, while the control group received the same volume of sterile saline (NS) subcutaneously in the neck and back. The depression model was established for 6 weeks, and the mice's condition and behavioral indicators were observed to confirm successful model establishment. All mice were fed and hydrated normally, and the room temperature was (24 ± 2) ℃. After successful modeling, the model group was further divided into three groups: the model group, the vitamin E group, and the combination group. The vitamin E group (0.2 mL / day / mouse) and the combination group (0.2 mL / day / mouse) received oral vitamin E solution for 4 weeks, while the model group and the control group received the same volume of NS.

[0028] Indicator Testing: 1. Hanger test The coat hanger test is commonly used to detect behavioral despair in mice. This experiment was conducted 4 weeks after drug administration. The coat hanger was approximately 35 cm long and 3 mm in diameter, suspended from a metal frame at a height of approximately 40 cm above the ground. Initially, the mice were placed upside down in the middle of the horizontal bar. The mice were observed for 30 seconds, and their scores were recorded. Simultaneously, their motor abilities were observed, recording the time it took for the mice to reach either end of the horizontal bar within 120 seconds, or the time it took to fall off the bar. The experiment was conducted twice, once in the morning and once in the afternoon. The scoring criteria for the mice within 30 seconds are shown in Table 1.

[0029] Table 1 Scoring criteria for the clothes hanger experiment within 30 seconds Table 1 Rating criteria for coat hanger experiment with in 30s 2. Perform a nest test. The nest-building test is a method to evaluate the nest-building ability of mice and is suitable for reflecting changes in the daily behavioral motivation and emotional state of mice. First, before 21:00 at night, move the experimental mouse cages to a quiet and clean room (room temperature 25 ℃), and then place each mouse individually in a cage containing corn cob, water, food, and an equal amount of defatted cotton. Second, use tags to record the mouse's group type and number in detail and mark them on the mouse cages. Finally, observe the nest-building situation of the mice at 9:00 the next morning (12 hours later) and take photos to record the results. The evaluation criteria for the quality of nest-building by mice are shown in Table 2.

[0030] Table 2. Nest-building ability scoring table for experimental mice Table 2 Scoring table of nest building ability of experimental mice 3. Sucrose preference test (SPT) SPT (Sugar Preference Test) can evaluate depression and related emotional states in mice. The sucrose preference test consists of two parts: adaptation training and testing. Before the experiment, mice were placed alone in the laboratory and allowed to acclimatize for 48 hours. For the first 24 hours of training, two bottles of 2.0% sucrose solution were placed in each cage. After 24 hours, one of the bottles was replaced with sterile purified water. After training, the mice were fasted and deprived of water for 24 hours. During the test, the two pre-selected water bottles (one containing 2.0% sucrose solution and the other containing sterile purified water) were weighed. All animals were fasted during this process. After 12 hours, the two water bottles were removed and weighed again. The total fluid consumption, sucrose solution consumption, and purified water consumption of the mice were recorded.

[0031] 4. Brain tissue pathological examination At the end of the 10-week period following the last administration, mice were fasted overnight, weighed, and euthanized by cervical dislocation. The extracted hippocampal body tissue was mechanically homogenized with normal saline (NS) at a 1:9 ratio and centrifuged at 2500 rpm. The supernatant was collected and stored at -80 °C. Brain tissue specimens were fixed with 10% fixative, and the hippocampal body was excised. The tissue was then subjected to gradient dehydration, clearing, paraffin embedding, and prepared into 4 μm paraffin sections. These sections were stained with hematoxylin and eosin (HE) and observed and photographed under an optical microscope. The dewaxed and rehydrated hippocampal body sections were stained with NEUN and GFAP antibodies using an immunohistochemical kit and mounted. Observation and photography were performed under high magnification (400 nm). A double-blind evaluation method was used to assess the positivity, and a positive score was calculated. Five fields of view were randomly selected from each section for scoring, and the mean score was calculated.

[0032] Experimental results: (1) The effect of the composition on improving the physical signs of depressed mice During the experiment, the mice's weight was monitored weekly. Figure 1As shown in Figure B, compared with the control group, mice injected with D-galactose experienced a significant decrease in body weight. Compared with the model group, mice in the vitamin E and combination groups experienced a slower decrease in body weight. Simultaneously, significant signs of depression were observed in the model group mice, including reduced food intake, lethargy, listlessness, and brittle and dull fur. Compared with the model group, mice in the VE and combination groups showed improvements in general condition, including increased food intake, coat quantity and luster, and daily activity levels. Figure 1 A.

[0033] (2) The effect of the composition on improving behavioral despair in depressed mice To investigate the effect of the composition on behavioral despair in depressed mice, the coat hanger test was used. Lower scores and longer escape latency indicated more severe behavioral despair in the mice. Figure 2 In the model group (A), the clothes hanger score was 2.57 ± 1.05, significantly lower than that of the blank group (4.67 ± 0.47). However, the use of the composition or vitamin E significantly improved the clothes hanger score of mice, to 4.02 ± 0.63 and 4.50 ± 0.50, respectively. Figure 2 (A). Meanwhile, its escape incubation period is as follows: Figure 2 As shown in Figure B, the escape latency of the model group (113.86 ± 10.96 s) was significantly higher than that of the blank group (48.83 ± 14.70 s), while the escape latency of the combination group or vitamin E group was significantly reduced to 89.40 ± 15.47 s and 41.50 ± 16.87 s, respectively. Figure 2 (B). These results indicate that the composition can alleviate the symptoms of behavioral despair in mice.

[0034] (3) The effect of the composition on improving lack of motivation in depressed mice Nesting experiments are commonly used to assess the proactive behavior and motivation of mice. According to... Figure 3 The nesting ability score of the model group mice was 3.29 ± 0.70, significantly lower than that of the blank group (4.50 ± 0.50). However, the composition or vitamin E group significantly improved the nesting ability score of mice, at 4.25 ± 0.66 and 3.60 ± 0.80 respectively, significantly higher than that of the model group. This indicates that the composition can improve the lack of motivation symptoms in mice to some extent.

[0035] (4) The effect of the composition on improving anhedonia in depressed mice The sucrose preference test is a core and classic method for behavioral testing in depressed mice, primarily used to assess anhedonia. Experimental results show that, according to... Figure 4In the B group, the sucrose preference index of the model mice was 50.64 ± 0.63, significantly lower than that of the blank group (54.87 ± 0.36). However, the combination or vitamin E groups significantly increased the mice's preference for sucrose solution, with indices of 54.93 ± 0.61 and 54.42 ± 0.50, respectively. Figure 4 Furthermore, there was no significant difference in fluid intake among the experimental groups (P>0.05); these results indicate that the composition increased sucrose preference rate in mice, improved anhedonia, and exhibited an antidepressant effect.

[0036] (5) The effect of the composition on the improvement of brain tissue in depressed mice Depressed mice often exhibit morphological changes in their brain tissue. From mouse brain tissue ( Figure 5 As shown in Figure A), in the normal mouse hippocampus, the pyramidal cells in layers 3-4 of the CA1 region are arranged tightly and neatly, with clearly visible nuclei, nucleoli, and cytoplasm. In the brain tissue of the model group mice, the pyramidal cells are loosely arranged, and the neurons appear disordered, indicating structural changes due to neuronal damage, with some neurons even disappearing. In the combination therapy and vitamin E groups, the brain damage in mice is reduced, the number of neurons increases, and the cells are arranged in a regular and tight manner. The figures show that the neurons in the vitamin E group and the combination therapy group have essentially recovered to normal. NEUN analysis was used to assess the degree of damage to the hippocampus, and the co-localization of NEUN and DAPI staining in the cell nuclei revealed normal neurons. Figure 5 As shown in Figure B, under fluorescence microscopy, the number of normal neurons in the hippocampus of the model group was significantly reduced, while the number of normal neurons in the combined drug group significantly increased after drug treatment. The number of NEUN-positive cells in each group was as follows: 12.25 ± 2.14 normal neurons / HPF in the blank group, 5.57 ± 2.12 in the model group, 10.25 ± 2.41 in the VE group, and 11.35 ± 2.36 in the combined drug group. Compared with the model group, the number of normal neurons in the combined drug group was significantly increased (P<0.05). The degree of damage to astrocytes in the hippocampus of the brain tissue was assessed by GFAP analysis. Co-localization of GFAP and DAPI staining in the cell nuclei showed normal astrocytes. Figure 5As shown in Figure C, under fluorescence microscopy, the number of astrocytes in the hippocampus of the model group was significantly reduced. However, after drug treatment, the number of astrocytes in the hippocampus of the VE and combined drug groups was significantly increased. The number of GFAP-positive cells in each group showed that the number of normal astrocytes in the blank group was 10.65 ± 2.24 / HPF, in the model group it was 4.65 ± 1.25 / HPF, in the VE group it was 9.80 ± 2.31 / HPF, and in the combined drug group it was 9.68 ± 2.26 / HPF. Compared with the model group, the number of astrocytes in the combined drug group was significantly increased (P<0.05).

[0037] In summary, the composition exerts an antidepressant effect by inhibiting apoptosis of somatic neurons in the mouse hippocampus, alleviating hippocampal tissue damage, and thereby improving depressive-like behaviors such as behavioral despair, lack of motivation, and anhedonia.

[0038] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A composition for soothing the liver, relieving depression, calming the mind, and soothing the nerves, characterized in that, It was prepared from the following components in parts by weight: 15g lily bulb, 10g mint, 10g gardenia, and 10g jujube seed.

2. A method for preparing the composition according to claim 1, characterized in that, Includes the following steps: The lily bulbs, mint, gardenia, jujube seeds, and water are mixed and soaked to obtain the soaking material; The soaking material obtained in step 1) is decocted, and the resulting decoction is dried to obtain the composition.

3. The preparation method according to claim 2, characterized in that, In step 1), the total mass ratio of the four components—lily, mint, gardenia, and jujube seed—to water is 1:

10.

4. The preparation method according to claim 2, characterized in that, The soaking time in step 1) is 2 hours.

5. The preparation method according to claim 2, characterized in that, The conditions for decocting in step 2) include: decocting twice, 30 minutes each time.

6. The preparation method according to claim 2, characterized in that, The drying conditions in step 2) include: combining the decoctions obtained from two decoctions and filtering them; removing most of the water from the filtrate using a rotary evaporator; and drying in an 80°C oven until it is dried into powder.

7. The use of the composition according to any one of claims 1-6 in the preparation of products having the functions of soothing the liver and relieving depression, calming the mind and soothing the nerves.

8. A composition for soothing the liver, relieving depression, calming the mind, and soothing the nerves, comprising the composition according to any one of claims 1-6 and medically acceptable excipients.

Images