Traditional Chinese medicine preparations for treating or improving depression

Abstract

The present invention provides a kind of Chinese medicine preparation for treating or improving depression, and relates to the technical field of Chinese medicine pharmacy.Chinese medicine preparation of the present invention is made of 10 medicinal materials in total, including safflower seeds, citron, toosendan seeds, cyperus rotundus, herba communis, senecio, fennel, jujube, fenugreek, and liquorice. All medicines are used to soothe the liver and regulate qi, clear the liver and purge fire, regulate the liver and spleen, and clear the meridians and warm the kidney yang, so that liver depression can be solved, qi can be smooth, liver fire can be cleared, and depression can be removed.Chinese medicine preparation of the present invention has a significant improvement effect on the depressive-like behavior of depression mice, and has a significant inhibitory effect on neuroinflammation. At the same time, Chinese medicine preparation of the present invention is combined with western medicine to treat depression, and has a significant effect, which can significantly reduce the HAMD-17, HAMA and TESS scores of depression patients after treatment, significantly improve the depression and anxiety of patients, and alleviate adverse reactions. Chinese medicine preparation of the present invention provides a new idea for traditional Chinese medicine treatment of depression.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine pharmaceutical manufacturing, and in particular to a traditional Chinese medicine preparation for treating or improving depression. Background Art

[0002] Depression is a common mental and emotional disorder that poses a threat to human physical and mental health. Its main clinical manifestations include low mood, slowed thinking and behavior, unresponsiveness, loss of interest, and pessimism and despair. It is characterized by high prevalence, recurrence, and disability rates. According to the World Health Organization, 3% to 5% of the global population suffers from the disorder, with a prevalence of 4.4% and 4.2% in my country, making it a serious public health problem. Currently, Western medicine primarily treats depression with chemical antidepressants such as fluoxetine, paroxetine, and escitalopram. While these medications have some antidepressant effects, they can still suffer from slow onset, significant side effects, high dependency, and even depression resistance in some patients.

[0003] Traditional Chinese Medicine classifies depression as "depression," a disorder of the emotions. Depression can be broadly and narrowly defined. Broadly speaking, it refers to sluggish Qi flow, the six exogenous pathogenic Qi, and emotional stagnation, encompassing the Five Movements, Zang-Fu, and Six Depressions. Narrowly defined, depression often results from emotional frustration or sluggish Qi flow, leading to prolonged stagnation, such as visceral agitation and plum-pit qi. Clinical manifestations include depressed mood, tearful feelings, and insomnia, and can be accompanied by somatic symptoms such as chest and flank fullness and discomfort, and a feeling of a lump in the throat. The primary site of the disease is the liver, with close connections to the heart and spleen. Currently, traditional Chinese medicines used clinically to treat depression primarily target the liver, relieving depression through this process, and are often used as adjunctive medications for depression. Traditional Chinese medicines and their compound formulations, due to their multi-pathway, multi-component, multi-target synergy, and minimal side effects, have achieved significant efficacy in treating depression, such as Jieyu Pills, Danzhi Xiaoyao Powder, and Shugan Jieyu Capsules. The present invention aims to provide a safe, effective, and highly effective traditional Chinese medicine preparation for treating or ameliorating depression. Summary of the Invention

[0004] (1) Technical problems solved

[0005] In view of the deficiencies of the prior art, the present invention provides a safe, effective and therapeutically effective traditional Chinese medicine preparation for treating or improving depression.

[0006] (2) Technical solution

[0007] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0008] The present invention provides a traditional Chinese medicine preparation for treating or improving depression. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 5-25 parts of salvia officinalis seeds, 5-25 parts of citron, 5-25 parts of toosendan seeds, 1-20 parts of liquidambar formosana, 1-20 parts of Prunus mume seeds, 5-25 parts of communis herba, 1-20 parts of senecio scabra, 5-25 parts of amaranthus chinensis seeds, 1-20 parts of fenugreek seeds, and 1-10 parts of liquorice.

[0009] Furthermore, the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 10-20 parts of salvia officinalis seeds, 10-20 parts of citron, 10-20 parts of toosendan seeds, 5-15 parts of rhizoma liquidambar formosana, 5-15 parts of prunus mume seeds, 10-20 parts of communis herba, 5-15 parts of senecio scabra, 10-20 parts of amaranthus chinensis seeds, 5-15 parts of fenugreek seeds, and 5-10 parts of licorice.

[0010] Furthermore, the Chinese medicine preparation is made from the following raw materials in parts by weight: 12 parts of salvia officinalis seeds, 12 parts of citron, 12 parts of toosendan seeds, 10 parts of rhizoma liquidambar formosana, 12 parts of Prunus mume seeds, 15 parts of communis, 10 parts of senecio serrata, 12 parts of amaranth seeds, 10 parts of fenugreek, and 6 parts of licorice.

[0011] The Chinese medicine preparation provided by the present invention is used to prepare a drug for treating or improving depression. The Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions, lyophilized powders or other pharmaceutically acceptable oral dosage forms according to conventional pharmaceutical preparation methods in pharmacy and with medically acceptable excipients.

[0012] Sago seed: warm in nature, sweet in taste, enters the liver and stomach meridians; has the effects of relieving fullness, regulating qi, harmonizing the stomach, and relieving pain; it mainly contains triterpenoid saponins, flavonoids, coumarins, indole alkaloids and fatty oils; modern pharmacological research shows that Sago seed has multiple pharmacological activities such as anti-inflammatory, antioxidant, anti-tumor, and neuroprotection.

[0013] Citron: It tastes pungent, bitter, and sour, and is warm in nature. It enters the liver, spleen, and lung meridians. It has the effects of soothing the liver and regulating qi, relieving fullness, and resolving phlegm. It is used to treat liver and stomach qi stagnation, chest and flank pain, abdominal distension, vomiting and belching, cough with phlegm, etc. Citron contains a variety of active chemical substances such as volatile oils, flavonoids, coumarins, alkaloids, etc., which have various pharmacological effects such as antioxidant, antibacterial, anti-diabetic, and lipid-lowering.

[0014] Toosendan fruit: bitter and cold in nature, slightly toxic, enters the liver, small intestine and bladder meridians; has the effects of soothing the liver and relieving heat, promoting qi circulation and relieving pain, and killing insects; mainly contains volatile oils, lignans, organic acids, flavonoids, limonoids and other ingredients; modern pharmacological research shows that Toosendan fruit has anti-inflammatory, analgesic, and neuroprotective effects on the central nervous system, as well as antioxidant, insecticidal, antibacterial, antiviral, and anti-tumor effects.

[0015] Lulutong: Bitter in taste, neutral in nature; enters the liver and kidney meridians; dispelling wind and dampness, soothing the liver and activating the collaterals, promoting diuresis and menstruation, and is used to treat conditions such as water retention, insufficient milk production, and amenorrhea. Lulutong primarily contains betulinic acid, gallic acid, lulutongone A, and other terpenoid, aliphatic, and aromatic compounds; it exhibits anti-inflammatory, neuroprotective, antioxidant, and anti-tumor effects.

[0016] Prunus mume seed: Pungent, bitter, sweet, neutral. It enters the spleen, large intestine, and small intestine meridians. It moisturizes and lubricates the intestines, relieves qi, and promotes diuresis. It is used to treat dryness and intestinal dryness caused by fluid depletion, food stagnation and qi stagnation, abdominal distension and constipation, edema, beriberi, and dysuria. It has the effects of moisturizing and lubricates the intestines, relieving qi stagnation, and promoting diuresis and reducing swelling. It contains flavonoids, fatty acids, amino acids, glycosides, and mineral elements, and has multiple pharmacological effects, including moisturizing and lubrication, anti-inflammatory, analgesic, antioxidant, anti-aging, and anti-tumor.

[0017] Commelina: sweet, light in taste, cold in nature, enters the lung, stomach and small intestine meridians, has the effects of clearing heat and purging fire, detoxifying, promoting diuresis and reducing swelling, and is used for colds and fever, fever and thirst, delayed swelling and pain, edema and oliguria, and hot stranguria and pain; its main active ingredients are flavonoids and alkaloids, and it has multiple pharmacological effects such as antioxidant, antihypertensive, lipid metabolism regulation, anti-inflammatory and analgesic, antiviral, and antibacterial.

[0018] Senecio: bitter in taste, cold in nature, enters the lung and liver meridians; has the effects of clearing away heat and detoxifying, improving eyesight, promoting dampness, killing insects and relieving pain; used for carbuncle, fever and cold, red and swollen eyes, diarrhea, dysentery, skin eczema and other diseases; mainly contains seneciopine, seneciopine, lupenone, oleanane, β-sitosterol, carotene, alkaloids, p-hydroxyphenylacetic acid, hyperoside, montanol, oleanol, quercetin, racemic syringaresinol, emodin, chlorogenic acid, caffeic acid and other ingredients, has a strong antibacterial effect on Staphylococcus aureus, Salmonella typhi, Salmonella paratyphi A, Salmonella paratyphi B, Shigella dysenteriae, Shigella boydii and Shigella sonnei.

[0019] Amaranthus seeds: Bitter, slightly cold. Enters the Liver Meridian. Clears the liver, brightens the eyes, and removes cataracts. Used for liver-heat-induced red eyes, cataract formation, blurred vision, and dizziness caused by liver fire. Modern pharmacological research indicates that Amaranthus seeds have multiple effects, including hepatoprotective, anti-cataract, anti-tumor, immunomodulatory, anti-diabetic, and antibacterial properties.

[0020] Fenugreek: warm in nature, bitter in taste; has the effects of warming the kidney, dispelling cold and relieving pain; used for kidney deficiency and cold, lower abdominal cold pain, small intestinal hernia, cold and damp athlete's foot and other symptoms; it mainly contains steroidal saponins, flavonoids, terpenes, alkaloids, fats and oils, amino acids and proteins and other active ingredients; modern pharmacological research shows that fenugreek has multiple effects such as lowering blood sugar, lowering blood lipids, anti-oxidation, anti-tumor, analgesic and anti-inflammatory.

[0021] Licorice: sweet in taste, neutral in nature, enters the heart, spleen, lung, and stomach meridians; has the effects of tonifying the spleen and replenishing qi, clearing away heat and detoxifying, removing phlegm and relieving cough, relieving acute pain, and harmonizing various medicines; it is used for spleen and stomach weakness, fatigue, palpitations and shortness of breath, cough and sputum, carbuncles, sores and other symptoms. Licorice is also good at harmonizing the properties of medicines and alleviating the toxicity of drugs.

[0022] (3) Beneficial effects

[0023] The traditional Chinese medicine preparation of the present invention is prepared from ten medicinal materials in total, namely, sago seed, citron, toosendan fruit, amaranth fruit, communis herb, senecio herb, rhizoma schizonepetae, prunus mume seed, fenugreek and licorice. In the prescription, sago seed can soothe the liver and regulate qi, harmonize the stomach and relieve pain; citron can dry out dampness and resolve phlegm, enter the spleen and stomach to promote qi and relieve fullness; the two medicines are used together to soothe the liver and relieve depression to relieve stagnation, regulate qi, relieve fullness and harmonize the spleen and stomach, and are the main medicines; toosendan fruit is used to soothe the liver and relieve heat, promote qi and relieve pain; amaranth fruit is used to clear the liver and relieve fire; communis herb clears dampness and heat; senecio herb clears heat and detoxifies, improves eyesight and removes dampness; the four medicines are used together to promote each other, can clear liver fire, promote qi stagnation, and have the effects of clearing heat and purging fire, calming liver yang, and relieving dryness and restlessness. The herb is supplemented with Rhizoma Lulutong to dispel wind, activate collaterals, promote diuresis and dredge menstruation; Prunus mume to moisten the intestines and relieve qi; and Fenugreek to warm the kidneys and support yang, regulating yang deficiency and poor qi transformation. Licorice to replenish qi, tonify the middle, and alleviate liver urgency, thus achieving a harmonizing effect. These four herbs together serve as adjuvants. The combination of these herbs can soothe the liver and regulate qi, clear the liver and purge fire, harmonize the liver and spleen, dredge the meridians, and warm the kidney yang, thereby relieving liver depression, promoting qi flow, clearing liver fire, and eliminating depression.

[0024] The Chinese medicine preparation of the present invention has a significant improvement effect on the depressive-like behavior of depressed mice; it can significantly reduce the content of pro-inflammatory factors in the hippocampus of depressed mice, significantly increase the content of anti-inflammatory factors in the hippocampus of depressed mice, and can also significantly inhibit the pro-inflammatory M1 polarization of microglia in the DG brain region of the hippocampus of depressed mice, and has a significant inhibitory effect on neuroinflammation. At the same time, the Chinese medicine preparation of the present invention is effective in treating depression in combination with Western medicine, can significantly improve the total effective rate of treating depression, can significantly reduce the HAMD-17, HAMA and TESS scores of depressed patients after treatment, significantly improve the depression and anxiety of patients, and reduce adverse reactions. The Chinese medicine preparation of the present invention provides a new idea for the treatment of depression with traditional Chinese medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The results of fluorescence detection of pro-inflammatory M1 polarization of microglia in the DG region of the hippocampus of mice in each group. The white arrows indicate M1 polarized cells.

[0026] Figure 2 Comparison of HAMD-17 scores before and after treatment between the two groups of patients; compared with the same group before treatment, ** P <0.01; compared with the control group, ## P <0.01.

[0027] Figure 3 Comparison of HAMA scores before and after treatment between the two groups of patients; compared with the same group before treatment, ** P <0.01; compared with the control group, ## P <0.01.

[0028] Figure 4 Comparison of TESS scores between the two groups of patients after 8 weeks of treatment; compared with the control group,* P <0.05. DETAILED DESCRIPTION

[0029] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention. Example 1

[0030] A traditional Chinese medicine preparation for treating or improving depression is prepared from the following raw materials in parts by weight: 8 parts of salvia officinalis seeds, 8 parts of citron, 8 parts of toosendan seeds, 4 parts of liquidambar formosana, 8 parts of Prunus mume seeds, 8 parts of communis herba, 8 parts of senecio serrata, 8 parts of amaranthus chinensis seeds, 4 parts of fenugreek seeds, and 2 parts of liquorice.

[0031] The Chinese medicine preparation provided by the present invention is used to prepare a drug for treating or improving depression. The Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions, lyophilized powders or other pharmaceutically acceptable oral dosage forms according to conventional pharmaceutical preparation methods in pharmacy and with medically acceptable excipients. Example 2

[0032] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 24 parts of salvia officinalis seeds, 22 parts of citron, 22 parts of toosendan seeds, 18 parts of rhizoma liquidambar formosana, 16 parts of Prunus mume seeds, 22 parts of communis herba, 16 parts of senecio serrata, 22 parts of amaranthus chinensis seeds, 16 parts of fenugreek seeds, and 8 parts of liquorice. Example 3

[0033] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 16 parts of salvia officinalis seeds, 14 parts of citron, 14 parts of toosendan seeds, 12 parts of rhizoma liquidambar formosana, 16 parts of Prunus mume seeds, 18 parts of communis herba, 16 parts of senecio serrata, 14 parts of amaranthus chinensis seeds, 16 parts of fenugreek seeds, and 7 parts of liquorice. Example 4

[0034] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 10 parts of salvia officinalis seeds, 10 parts of citron, 10 parts of toosendan seeds, 5 parts of rhizoma liquidambar formosana, 5 parts of Prunus mume seeds, 10 parts of communis herba, 5 parts of senecio serrata, 10 parts of amaranthus chinensis seeds, 5 parts of fenugreek seeds, and 5 parts of liquorice. Example 5

[0035] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 20 parts of sago seeds, 20 parts of citron, 20 parts of toosendan seeds, 15 parts of rhizoma liquidambar formosana, 15 parts of prunus mume seeds, 20 parts of communis, 15 parts of senecio, 20 parts of amaranth seeds, 15 parts of fenugreek, and 10 parts of liquorice. Example 6

[0036] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 16 parts of salvia officinalis seeds, 16 parts of citron, 14 parts of toosendan seeds, 10 parts of liquidambar formosana, 12 parts of Prunus mume seeds, 14 parts of Commelina communis, 12 parts of Senecio chinensis, 16 parts of Amaranthus chinensis seeds, 8 parts of fenugreek, and 8 parts of liquorice. Example 7

[0037] The difference between this embodiment and embodiment 1 is that the traditional Chinese medicine preparation is made from the following raw materials in parts by weight: 12 parts of sago seeds, 12 parts of citron, 12 parts of toosendan seeds, 10 parts of rhizoma liquidambar formosana, 12 parts of Prunus mume seeds, 15 parts of communis, 10 parts of senecio, 12 parts of amaranth seeds, 10 parts of fenugreek, and 6 parts of liquorice.

[0038] Test Example 1

[0039] 1 Materials and Methods

[0040] 1.1 Preparation of experimental animals and depression mouse models

[0041] Sixty SPF-grade male ICR mice, weighing 20 ± 2 g, were provided by Beijing Weitonglihua Laboratory Animal Technology Co., Ltd.

[0042] Mice were acclimated for one week and randomly divided into a normal group (10 mice) and a model group (50 mice). The model group was housed individually and subjected to randomized chronic unpredictable mild stimulation to establish a depression model. Chronic unpredictable mild stimulation methods included: tilted cage (45°), wet cage (24 hours), strobe light (300 flashes / min), noise (70 dB), water deprivation (12 hours), overnight lighting (12 hours), restraint (4 hours), day / night reversal (24 hours), pair housing (12 hours), empty bottle stimulation (1 hour), and ice water swimming (4°C, 5 minutes). Three to four randomized stimulations were administered daily for six consecutive weeks, with the order of stimulation randomly altered.

[0043] 1.2 Trial Drugs

[0044] The Chinese medicine preparation of the present invention is as follows: weigh the following raw materials according to the following weight parts: 12 parts of sarophora seeds, 12 parts of citron, 12 parts of toosendan seeds, 10 parts of fennel seeds, 12 parts of rhizoma schizonepetae, 15 parts of coleus, 10 parts of senecio, 12 parts of amaranth seeds, 10 parts of fenugreek, and 6 parts of licorice, wash them, soak them in 3 times deionized water for 30 minutes, then decoct them for 40 minutes, repeat the decoction for more than 2 times, collect the decoction, concentrate the decoction to 1 g / mL (1 mL contains 1 g of crude drug), and store them at 4°C for later use.

[0045] Western medicine control: Paroxetine

[0046] Chinese medicine comparison: Danzhi Xiaoyao Powder

[0047] 1.3 Experimental Grouping and Treatment

[0048] After six weeks of chronic unpredictable mild stimulation, 50 mice were randomly divided into five groups: a model group, a Western medication positive control group (paroxetine, 20 mg / kg), a traditional Chinese medicine positive control group (Danzhi Xiaoyao San, 7 g / kg), a high-dose group (8.6 g / kg, referred to as the high-dose group), and a low-dose group (4.3 g / kg, referred to as the low-dose group). Each group contained 10 mice. The mice were gavaged for four consecutive weeks, during which they continued to receive chronic mild stimulation. Ten healthy mice served as a blank control group and received an equal dose of saline. After the last dose, the mice in each group were evaluated for depressive-like behavior using sucrose preference, forced swimming, tail suspension, and open field tests. After behavioral testing, the mice were sacrificed, serum was collected, and hippocampal tissue was isolated on ice and stored at -80°C for subsequent experiments.

[0049] 1.4 Detection indicators

[0050] 1.4.1 Sugar Preference Test (SPT)

[0051] After the final drug administration, mice were deprived of food and water for 24 hours. Pre-weighed 1% sugar water and tap water were then administered. Six hours later, the water bottles were swapped. Twelve hours later, the water bottles were collected and weighed, and sugar and tap water intake was calculated. Sugar water preference was defined as sugar water intake divided by the sum of sugar and tap water intake.

[0052] 1.4.2 Behavioral testing

[0053] 1.4.2.1 Forced Swim Test (FST)

[0054] Mice were acclimated to the testing environment for 2 hours beforehand. They were placed in a 5 L transparent glass container (18 cm in diameter, 26.5 cm in height), approximately 15 cm deep, and maintained at 25°C. After administration, the mice were gently placed in the water. The mice's activity was recorded over a 6-minute period, and the last 4 minutes of activity were used to calculate the duration of swimming and immobility.

[0055] 1.4.2.2 Tail Suspension Test (TST)

[0056] Place the mouse gently in the palm of your hand and let it calm down for 5 minutes. Then use tape to gently fix the mouse's tail to the top of the experimental frame. Record the mouse's struggle within 6 minutes on video. Select the time in the last 4 minutes when the mouse's limbs and trunk are completely motionless.

[0057] 1.4.2.3 Open Field Test (OFT)

[0058] The animals' activity status was assessed by observing their voluntary movements. The number of movements, number of standing times, center distance traveled, center dwell time, and total distance traveled were recorded and analyzed.

[0059] 1.4.3 Detection of inflammatory factors in hippocampal tissue

[0060] Elisa kits were used to detect the expression changes of pro-inflammatory factors (TNF-α, IL-1β) and anti-inflammatory factors (IL4, IL10) in hippocampal tissue protein homogenate.

[0061] 1.4.4 Detection of microglial inflammatory polarization

[0062] Paraffin sections of hippocampal tissue were immunofluorescently stained with antibodies to microglial M1 polarization marker proteins (Iba-1 and CD68), and photographed under a laser confocal microscope.

[0063] 1.5 Statistical analysis

[0064] SPSS 21.0 was used for statistical analysis, and one-way analysis of variance was used for comparison between groups. The results are expressed as mean ± standard deviation ( ± s) format, and t-test was used. P <0.05 was considered statistically significant.

[0065] 2 Results

[0066] 2.1 Effect of the Chinese medicine preparation of the present invention on depressive-like behavior in a mouse model of depression

[0067] The results are shown in Table 1. Compared with the blank control group, the model group mice showed a significantly reduced sucrose preference rate (P<0.05), significantly increased immobility time in the forced swim and tail suspension tests (P<0.01), and a significantly reduced central open field distance (P<0.01) despite a constant total distance traveled in the open field test. This indicates successful modeling. Compared with the model group, the depressive-like behavior of mice in all drug-treated groups was significantly improved. The Western medicine positive control group, high-dose and low-dose groups, and the low-dose group all significantly increased sucrose preference (P<0.05). Compared with the model group, the Chinese medicine positive control group, Western medicine positive control group, low-dose group, and high-dose group all significantly reduced the forced swim and tail suspension immobility time (P<0.05 or P<0.01) and increased the central open field distance traveled (P<0.05 or P<0.01). The above results show that the Chinese medicine preparation of the present invention can significantly improve the depressive-like behavior of depressed mice. The behavioral experimental results suggest that the Chinese medicine composition of the present invention has the effect of significantly improving depressive-like behavior, and the effect is better than the traditional Chinese medicine Danzhi Xiaoyaosan and is equivalent to the Western medicine paroxetine.

[0068] Table 1 Results of sugar water preference and depressive-like behavior tests in mice of each group

[0069]

[0070] Note: Compared with the blank control group, #: P < 0.05, ##: P < 0.01; compared with the model group, *: P < 0.05, **: P < 0.05; the same below.

[0071] 2.2 Effects of the Chinese medicine preparation of the present invention on inflammatory factors in the hippocampus of a mouse model of depression

[0072] The results are shown in Table 2. Compared with the blank control group, the model group mice showed significantly increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) (P<0.01, P<0.01), and significantly decreased levels of anti-inflammatory cytokines (IL-4, IL-10) (P<0.01, P<0.01). Compared with the model group, the Chinese medicine positive control group, the Western medicine positive control group, and the high- and low-dose groups all significantly decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β) (P<0.05 or P<0.01) and significantly increased levels of anti-inflammatory cytokines (IL-4, IL-10) (P<0.05 or P<0.01). These results demonstrate that the Chinese medicine preparation of the present invention has a specific and significant inhibitory effect on hippocampal neuroinflammation.

[0073] Table 2 Contents of anti-inflammatory and pro-inflammatory cytokines in the hippocampus tissue of mice in each group

[0074]

[0075] 2.3 Effect of the Chinese herbal preparation of the present invention on the pro-inflammatory M1 polarization of hippocampal microglia in a mouse model of depression

[0076] Neuroinflammatory disorders mediated by pro-inflammatory M1 polarization of hippocampal microglia are important pathogenic factors for depression. Figure 1 As shown in the figure, compared with the blank control group, the pro-inflammatory M1 polarization of microglia in the hippocampus DG of the model group mice (Iba + +CD68) increased significantly; compared with the model group, the Chinese medicine positive control group, the Western medicine positive control group, the high-dose and low-dose groups all significantly reduced the pro-inflammatory M1 polarization of microglia in the hippocampal DG brain region.

[0077] 3 Conclusion

[0078] The above results show that the Chinese herbal preparation of the present invention has a significant improvement effect on the depressive-like behavior of depressed mice; the Chinese herbal preparation of the present invention can significantly reduce the content of pro-inflammatory factors in the hippocampus of depressed mice, significantly increase the content of anti-inflammatory factors in the hippocampus of depressed mice, and at the same time, can significantly inhibit the polarization of pro-inflammatory M1 microglia in the DG brain region of the hippocampus of depressed mice, and the Chinese herbal preparation of the present invention has a significant inhibitory effect on neuroinflammation. The Chinese herbal preparation of the present invention has a significant therapeutic effect on depressed mice, comparable to the effect of the Western medicine paroxetine, and better than the Chinese medicine Danzhi Xiaoyaosan.

[0079] Test Example 2

[0080] 1 Materials and Methods

[0081] 1.1 General Information

[0082] A total of 78 patients with depression admitted to Pingyu County Hospital of Traditional Chinese Medicine between March 2023 and September 2024 were randomly divided into a control group and an observation group, with 39 patients in each group. The control group consisted of 19 males and 20 females, with a disease course of 1-6 years (mean, 3.09 ± 1.58) and an age range of 18-55 years (mean, 35.18 ± 6.81). The observation group consisted of 22 males and 17 females, with a disease course of 2-8 years (mean, 4.87 ± 2.06) and an age range of 18-60 years (mean, 38.17 ± 5.91). No significant differences in gender, disease course, age, and other general characteristics were found between the two groups (P > 0.05), indicating comparability between the two groups.

[0083] Inclusion criteria: ① meeting the diagnostic criteria for depression in the International Classification of Diseases 10 (ICD-10); ② Hamilton Depression Scale-17 Items (HAMD-17) score ≥ 17 points; ③ age 18-60 years; ④ no personality disorder and good social adaptation function.

[0084] Exclusion criteria: ① Serious tendency to harm oneself; ② Allergy or intolerance to study drugs; ③ Received systematic antidepressant treatment in the past 2 months, and depression-related symptoms have been basically relieved; ④ Concurrent malignant tumor; ⑤ Severe organic diseases such as heart, lung, liver, and kidney; ⑥ Pregnant or lactating women; ⑦ Hallucinations, delusions, or any psychotic symptoms during the current depressive episode; ⑧ Participated in a clinical trial in the past 90 days, or participated in two or more clinical trials in the past year.

[0085] 1.2 Methods

[0086] The control group was given sertraline hydrochloride tablets, 50 mg / time, once a day.

[0087] The observation group was treated with the Chinese medicine decoction of the present invention on the basis of the treatment of the control group, which specifically consisted of: 12g of salvia miltiorrhiza seeds, 12g of citron, 12g of toosendan seeds, 10g of fennel seeds, 12g of rhizoma liquidambar formosana, 12g of Prunus mume seeds, 15g of herba communis, 10g of senecio radix, 12g of amaranthus chinensis seeds, 10g of fenugreek seeds, and 6g of liquorice. The decoction was taken once a day, divided into two doses, once in the morning and once in the evening.

[0088] Both groups were treated for 8 weeks.

[0089] 1.3 Observation indicators and efficacy evaluation criteria

[0090] (1) Mental state: HAMD-17 and Hamilton Anxiety Scale (HAMA) were used to evaluate the mental state of the two groups of patients before and after treatment.

[0091] (2) Clinical efficacy: The clinical efficacy was evaluated with reference to the HAMD-17 score reduction rate: cured means that the depressive symptoms disappeared and the mood was normal, with a score reduction rate ≥75%; markedly effective means that the depressive symptoms basically disappeared and the mood was basically normal, with a score reduction rate ≥50%; effective means that the depressive symptoms were alleviated and the mood was relatively stable, with a score reduction rate ≥25%; ineffective means that the depressive symptoms did not alleviate and the mood did not improve, with a score reduction rate <25%.

[0092] (3) Adverse reactions: After 8 weeks of treatment, the Treatment Emergent Symptom Scale (TESS) was used to evaluate the adverse reactions of the two groups of patients, including insomnia, drowsiness, nausea and vomiting, anorexia, dry mouth, and constipation. The severity was divided into 0 to 4 points, with 0 being the absence of this symptom; 1 being the occasional symptom; 2 being mild, with no effect on normal function; 3 being moderate, with an effect on normal function; and 4 being severe, with a significant impairment of normal function.

[0093] 1.4 Statistical analysis

[0094] SPSS 21.0 statistical software was used to express measurement data as mean ± standard deviation. Non-independent sample t-test was used between groups, paired sample t-test was used within groups, and count data were expressed as percentages. The comparison between groups was performed using χ2 test. 2 Test, P < 0.05 indicates that the difference is statistically significant.

[0095] 2 Results

[0096] 2.1 Comparison of HAMD-17 and HAMA scores between the two groups before and after treatment

[0097] The results are as follows Figure 2 、 Figure 3 As shown in the results, compared with those before treatment, the HAMD-17 and HAMA scores of the two groups of patients were significantly reduced after treatment (P < 0.01); after treatment, the HAMD-17 and HAMA scores of the observation group were significantly lower than those of the control group (P < 0.01).

[0098] 2.2 Comparison of clinical efficacy between the two groups of patients

[0099] The results are shown in Table 3. The total effective rate of the observation group was 94.87%, which was significantly higher than that of the control group (76.92%).

[0100] Table 3 Comparison of clinical efficacy between the two groups of patients (n / %)

[0101]

[0102] 2.3 Comparison of TESS scores between the two groups after 8 weeks of treatment

[0103] The results are as follows Figure 4 As shown in the data, the scores of insomnia, sleepiness, nausea and vomiting, dry mouth and constipation in the observation group were significantly lower than those in the control group, among which the scores of insomnia, sleepiness and nausea and vomiting in the observation group were significantly lower than those in the control group (P < 0.05).

[0104] 3 Conclusion

[0105] The preparation of the present invention is effective in treating depression in combination with Western medicine, can significantly improve the overall effective rate of treating depression, can significantly reduce the HAMD-17, HAMA and TESS scores of patients with depression after treatment, significantly improve the patients' depression and anxiety, and reduce adverse reactions. The Chinese medicine preparation of the present invention provides a new idea for the treatment of depression with traditional Chinese medicine.

[0106] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A Chinese medicine preparation for treating or improving depression, characterized in that: The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 5-25 parts of salvia officinalis seeds, 5-25 parts of citron, 5-25 parts of toosendan seeds, 1-20 parts of liquidambar formosana, 1-20 parts of Prunus mume seeds, 5-25 parts of communis, 1-20 parts of senecio serrata, 5-25 parts of amaranth seeds, 1-20 parts of fenugreek, and 1-10 parts of liquorice.

2. A Chinese medicine preparation for treating or improving depression according to claim 1, characterized in that The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 10-20 parts of salvia officinalis seeds, 10-20 parts of citron, 10-20 parts of toosendan seeds, 5-15 parts of rhizoma liquidambar formosana, 5-15 parts of prunus mume seeds, 10-20 parts of communis herba, 5-15 parts of senecio scabra, 10-20 parts of amaranthus chinensis seeds, 5-15 parts of fenugreek seeds and 5-10 parts of liquorice.

3. A Chinese medicine preparation for treating or improving depression according to claim 1, characterized in that The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight: 12 parts of salvia officinalis seeds, 12 parts of citron, 12 parts of toosendan seeds, 10 parts of rhizoma liquidambar formosana, 12 parts of prunus mume seeds, 15 parts of communis herba, 10 parts of senecio serrata, 12 parts of amaranthus chinensis seeds, 10 parts of fenugreek seeds and 6 parts of liquorice.

4. Use of the Chinese medicine preparation according to any one of claims 1 to 3 in the preparation of a drug for treating or improving depression, characterized in that: The Chinese medicine preparation is prepared into granules, powders, oral liquids, pills, decoctions, freeze-dried powders or other pharmaceutically acceptable oral dosage forms according to conventional pharmaceutical preparation methods in pharmacy, with medically acceptable excipients.

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