Traditional Chinese medicine composition with anti-depression effect

Abstract

The invention belongs to the field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine composition with an anti-depression effect, which is prepared from the following medicinal materials by weight: 6g of pericarpium citri reticulatae viride, 6g of pericarpium citri reticulatae, 6g of radix paeoniae alba, 6g of thunberg fritillary bulb, 4.5 g of rhizoma alismatis, 4.5 g of fried gardenia and 4.5 g of moutan bark. The composition regulates functions of hypothalamus-pituitary-adrenal axis (HPA axis) and repairs hippocampal neurons and relieves symptoms such as pleasant sensation loss and behavioral despair of depression patients by relieving qi stagnation, clearing heat, cooling blood, promoting diuresis and reducing phlegm. Experiments prove that the traditional Chinese medicine composition can remarkably improve the sweet water preference rate of depression rats, shorten the forced swimming immobility time, reduce the levels of CRH, ACTH and CORT of plasma and improve pathological injuries of hippocampus tissues. The composition adopts medicinal and edible medicinal materials, is small in side effect and high in safety, and can be prepared into an oral preparation for treating depression.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating depression. Background Art

[0002] Depression is a common mental disorder globally, mainly clinically manifested by significant and persistent low mood, decreased interest, reduced energy, and even suicide. However, modern medical research has found that the pathogenesis of depression is complex, involving multiple factors such as genetics, biochemistry, neuroendocrine, and environment. Among them, the hypothalamic-pituitary-adrenal axis dysfunction hypothesis, monoamine neurotransmitter and its receptor hypothesis, neuroplasticity and neurotrophic factor hypothesis, cell molecular mechanism hypothesis, inflammation and cytokine hypothesis, excitatory amino acid hypothesis, gut microbiota dysbiosis hypothesis, etc. are all considered to play important roles in the occurrence of depression. At present, the treatment of depression mainly includes drug treatment, psychotherapy, and comprehensive treatment. Synthetic second-generation antidepressant drugs are the first choice for clinical treatment of depression, but there are problems such as limited efficacy and side effects. Therefore, it is very urgent to explore drugs for treating depression with better efficacy, fewer adverse reactions, and higher safety. Summary of the Invention

[0003] Aiming at the problems existing in the prior art, the object of the present invention is a traditional Chinese medicine composition for treating depression. The traditional Chinese medicine composition provided by the present invention can quickly and effectively relieve depressive-like behaviors such as anhedonia and behavioral despair in patients, is convenient to take and absorb, has stable efficacy, and has no any toxic and side effects.

[0004] In order to achieve the above invention object, the present invention provides the following technical solutions.

[0005] The present invention discloses an antidepressant traditional Chinese medicine composition, which is characterized by being composed of the following raw materials in parts by weight: 6 g of green tangerine peel, 6 g of dried tangerine peel, 6 g of white peony root, 6 g of thunberg fritillary bulb, 4.5 g of oriental waterplantain rhizome, 4.5 g of cape jasmine fruit, 4.5 g of moutan bark.

[0006] Further, the preparation method of the composition includes: soaking the raw materials with 6 - 10 times the amount of distilled water, decocting twice, combining the filtrates and concentrating to a suspension with a crude drug concentration of 2 - 3 g / mL.

[0007] Further, the composition is used for preparing a drug for treating depression.

[0008] Furthermore, the depression includes depressive-like behaviors mainly manifested by anhedonia and behavioral despair.

[0009] Further, the dosage form of the composition is an oral preparation, including decoction, granule, tablet or capsule.

[0010] The present invention also discloses an antidepressant drug, which is characterized by comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0011] Furthermore, the above-mentioned traditional Chinese medicine composition is used in the preparation of a drug for regulating the function of the HPA axis and repairing hippocampal neuron damage.

[0012] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0013] 1. Compared with the commonly used small molecule chemical drugs in clinical practice, the remarkable effect of the drug of the present invention lies in.

[0014] (1) The present invention overcomes the disadvantages that small molecule chemical drugs can only temporarily relieve the clinical symptoms of depression but cannot cure it, and are prone to relapse. The present invention starts from the root cause of the disease, and under the guidance of the overall concept of traditional Chinese medicine and syndrome differentiation and treatment, regulates the balance of yin and yang throughout the body, and can effectively eradicate the cause of depression and prevent the recurrence of the disease.

[0015] (2) The pathogenesis of depression is complex. The present invention overcomes the difficulty of the single action target of small molecule chemical drugs, making the action range more comprehensive and lasting, and can effectively improve the hyperfunction of the hypothalamic-pituitary-adrenal cortex axis of the body and promote the repair of hippocampal neurons.

[0016] (3) Compared with the inevitable adverse reactions of small molecule chemical drugs and the risks of drug dependence caused by long-term use, the drug of the present invention uses the roots, stems, leaves, flowers, fruits and seeds of natural plants, and all the drugs in the whole formula are drugs that are both medicine and food as stipulated by the Food Safety Law and can be used for health care. It has obvious characteristics such as small side effects, high component safety and few adverse reactions.

[0017] 2. Compared with the existing invention technology of traditional Chinese medicine composition, the remarkable effect of the present invention lies in: Among the medicinal material raw materials adopted by the present invention, Qingpi with warm nature, bitter and pungent taste soothes the liver and breaks qi, eliminates stagnation and relieves indigestion; Chenpi with warm nature, bitter and pungent taste regulates qi and strengthens the spleen, dries dampness and resolves phlegm, and they are used as the monarch drugs together. Moutan Cortex with slightly cold nature, bitter and pungent taste clears heat and cools blood, promotes blood circulation and removes stasis; stir-fried Gardenia jasminoides Ellis with cold nature, bitter taste clears heat and cools blood, purges fire and relieves restlessness; Alisma orientale with cold nature, sweet and light taste clears heat and promotes diuresis, removes turbidity and reduces lipid are used as the ministerial drugs together. Fritillaria thunbergii with cold nature, bitter taste clears heat and resolves phlegm, aids metal to calm the liver; Paeonia lactiflora Pall with slightly cold nature, bitter and sour taste nourishes blood and softens the liver, suppresses liver yang are used as the assistant drugs together. The whole formula exerts the effects of breaking qi and relieving depression, clearing heat and cooling blood, promoting diuresis and resolving phlegm. Depression is a disease syndrome mainly characterized by qi stagnation, accompanied by fire transformed from long-term stagnation and phlegm formed by injury to yin. These 7 drugs complement each other and jointly play the effects of breaking qi and relieving depression, clearing heat and cooling blood, promoting diuresis and resolving phlegm, and effectively relieve depressive behaviors such as anhedonia and behavioral despair in depression. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1Effects of Huagan Decoction on the behavior of depressive rats. Among them, A shows the effect on the sucrose preference of depressive rats; B shows the effect on the open field test of depressive rats.

[0019] Figure 2 Effects of Huagan Decoction on plasma CRH, ACTH, and CORT in depressive rats.

[0020] Figure 3 Effects of Huagan Decoction on the CA1 region of the hippocampal tissue in depressive rats (HE, ×400). Specific implementation manners

[0021] The following further describes the present invention in detail with specific embodiments. However, this should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following embodiments. All technologies implemented based on the content of the present invention belong to the scope of the present invention.

[0022] Unless otherwise specified, the reagents and materials used in the present invention are all commercially available.

[0023] 1 Experimental materials.

[0024] 1.1 Experimental animals.

[0025] 24 SPF-grade male SD rats at 4 weeks of age, with a body weight of (200 ± 20) g, were purchased from Liaoning Changsheng Biotechnology Co., Ltd., license number: SCXK(Liao)2023-0002; the SPF-grade experimental animal center of Liaoning University of Traditional Chinese Medicine. They were allowed to freely eat and drink, with a temperature of 18 - 23°C and a humidity of 35% - 55%. They were fed under a 12h light-dark cycle and adaptively fed for 1 week. The animal management procedures and treatment methods strictly complied with the "Guide for the Care and Use of Laboratory Animals".

[0026] 1.2 Drugs and reagents.

[0027] Composition of Huagan Decoction: 6g of Pericarpium Citri Reticulatae Viride, 6g of Pericarpium Citri Reticulatae, 6g of Radix Paeoniae Alba, 6g of Bulbus Fritillariae Thunbergii, 4.5g of Rhizoma Alismatis, 4.5g of Fructus Gardeniae, 4.5g of Cortex Moutan. The medicinal materials were purchased from the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine and were qualified by the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine. The above medicinal materials were soaked in 8 times the amount of distilled water overnight. For the first decoction, 8 times the amount of water was added and decocted for 2h, and for the second decoction, 6 times the amount of water was added and decocted for 1.5h. The medicinal liquids obtained by filtering the two decoctions were mixed and heated and concentrated into a suspension with a concentration of 2.7g / mL, placed in a refrigerator at 4°C for refrigeration, and rewarmed before use; corticotropin-releasing hormone (CRH), rat adrenocorticotropic hormone (ACTH), plasma corticosterone (CORT) ELISA kits (Shanghai Enzyme-linked Biotechnology Co., Ltd., batch numbers were ml132569, ml1887459, ml1397789 respectively); hematoxylin staining solution (Sigma Company, USA, batch number H9627); eosin staining solution (Sinopharm Chemical Reagent Co., Ltd., batch number 71014544).

[0028] 1.3 Instruments.

[0029] MIKRO 220 type ultra-high speed low-temperature centrifuge (Hettich Company, Germany); CX23 optical microscope (Olympus Biotechnology Co., Ltd.); embedding machine (Leica Company, Germany); HS-S7220-B type electric paraffin slicer (Shenyang Hengsong Technology Co., Ltd.); microscope (Leica Company, Germany); BDF-86V158 low-temperature refrigerator (BIOBASE Biotechnology Co., Ltd.).

[0030] 2 Experimental methods.

[0031] 2.1 Model establishment and drug administration.

[0032] After 7 days of adaptive feeding, 24 male SD rats were randomly divided into 4 groups with 6 rats in each group, namely: normal control group (NC), model group (CUMS), low-dose Huagan Decoction administration group (HGJ-L, 8 g / kg), and high-dose administration group (HGJ-H, 20 g / kg). NC rats were group-housed and fed and watered freely. The remaining groups were singly housed. The model was established by the method of chronic mild unpredictable stress (CUMS). The specific methods included swimming in ice water (4°C, for 5 min), heat stimulation (45°C, for 5 min), tail clamping (for 1 min), water deprivation (24 h), food deprivation (24 h), circadian rhythm reversal, wet bedding, etc. The stimulation was carried out for a total of 21 days. Each stress method was randomly arranged to ensure that the stimulation in adjacent 2 days was not repeated, so as to make the occurrence of unpredictable stimulation in rats. After the model was successfully established, the intervention groups of Huagan Decoction were orally administered the corresponding drugs, and the rats in the normal control group and the model group were intragastrically administered an equal amount of normal saline at the same time. During the drug intervention period, each model group continued to be stimulated for 21 days.

[0033] 2.2 Specimen collection.

[0034] After the behavioral detection, the rats in each group were anesthetized by intraperitoneal injection of 3% sodium pentobarbital. First, 2 rats were randomly selected from each group, and the chest and abdomen were dissected to fully expose the heart, liver, and aortic positions. The left ventricle was punctured into the ascending aorta, and the right auricle was cut open as an outlet. Normal saline was rapidly perfused. After the liver turned white, 4% paraformaldehyde was slowly perfused for fixation. The hippocampal tissue was taken out and fixed in 4% paraformaldehyde fixative for 24 h for morphological observation. The remaining 4 rats in each group had 5 mL of blood taken from the abdominal aorta and placed in an anticoagulant tube for standby. Then, the rats were decapitated, and the bilateral hippocampal tissues were quickly separated on ice and stored in a liquid nitrogen tank for molecular biology detection.

[0035] 2.3 Detection of the levels of CRH, ACTH, and CORT in rat plasma.

[0036] After the last administration, the rats were fasted for 12 h with free access to water. The rats in each group were anesthetized by intraperitoneal injection of 3% sodium pentobarbital. 5 mL of blood was taken from the abdominal aorta and placed in an anticoagulation tube, centrifuged at 3500 r / min for 15 min, and the supernatant was taken and stored at -80 °C in a refrigerator for later use. The levels of CRH, ACTH, and CORT in the rats were detected by ELISA assay. The operation process was carried out strictly according to the instructions of the ELISA kit. The standard curve was made based on the standard products, and the corresponding concentrations of the data in each group were calculated.

[0037] 2.4 Morphological observation of the hippocampal tissue of rats.

[0038] The fixed hippocampal tissue of the rats was taken out, and then successively treated with 70%, 80%, 90%, and 95% alcohol for 1 - 2 h each, and 100% alcohol was used for dehydration twice, 30 min each time. After dehydration, it was put into xylene for clearing for 15 - 30 min, and then immersed in paraffin at 56 - 58 °C for 2 - 3 h (changing the wax twice during this period). Subsequently, the wax-impregnated tissue was put into an embedding mold and embedded with paraffin. The embedded block was cut into 4 - 6 μm sections with a microtome, spread on a glass slide with warm water, and baked at 60 °C for 1 - 2 h. After that, the glass slide was successively dewaxed with xylene, hydrated with different concentrations of alcohol gradients, and washed with distilled water. Then the cell nuclei were stained with hematoxylin for 5 - 10 min, rinsed with tap water for bluing, differentiated with 1% hydrochloric acid alcohol and then washed with water, and the cytoplasm was stained with eosin for 2 - 5 min. Finally, it was dehydrated with alcohol, cleared with xylene, and sealed with neutral gum to make a specimen for long-term preservation and microscopic examination. The ImageJ software was used to perform the pathological scoring of the hippocampal tissue of the rats to evaluate the degree of damage to the hippocampal tissue of the rats.

[0039] 3 Results.

[0040] 3.1 General conditions of the rats.

[0041] At the end of the experiment, the hair of the rats in the normal group was white and shiny, they moved freely, responded quickly, and their eating, drinking, urination, and defecation were all normal, and their body types were fatter than those of the rats in the model group. The hair of the rats in the model group was dry, yellowish, dull and without luster, their mental state was poor, they arched their backs and curled up, remained dull and motionless, preferred to lean on the corner of the rat cage, and their body types were thin. After the intervention of the low and high-dose groups of Huaganjian, the hair, diet, stool, mental state, body weight, etc. were all improved compared with the model group, and the effect of the high-dose group of Huaganjian was the most obvious.

[0042] 3.2 Effects of Huaganjian on the behavior of depressive rats.

[0043] 3.2.1 Effects on the sucrose preference of depressive rats.

[0044] Before the experiment, there was no significant difference in the sucrose preference rate among rats in each group. After 21 days of modeling, compared with the normal group, the sucrose preference rate of rats in the model group decreased significantly (P<0.01), and the difference was statistically significant. After 21 days of administration, compared with the model group, the sucrose preference rates of the low- and high-dose groups of Huaganjian increased significantly (P<0.01). See Figure 1 A.

[0045] 3.2.2 Effects on the open field test of depressive rats.

[0046] Before the experiment, there was no significant difference in the immobility time of rats in each group during forced swimming. After 21 days of modeling, compared with the normal group, the immobility time of rats in the model group during forced swimming was significantly prolonged (P<0.01), and the difference was statistically significant. After 21 days of administration, compared with the model group, the immobility times of the low- and high-dose groups of Huaganjian during forced swimming were significantly shortened (P<0.05, P<0.01). See Figure 1 B.

[0047] 3.3 Effects of Huaganjian on plasma CRH, ACTH, and CORT in depressive rats.

[0048] After 21 days of administration, compared with the normal group, the contents of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the plasma of rats in the model group were significantly increased, and the difference was statistically significant. Compared with the model group, the contents of plasma CRH, ACTH, and CORT in the low- and high-dose groups of Huaganjian were significantly decreased. The results showed that Huaganjian could relieve the hyperactive state of the HPA axis in depressive rats. See Figure 2 .

[0049] 3.4 Effects of Huaganjian on the pathological morphology of the hippocampal tissue in depressive rats.

[0050] The neurons in the CA1 region of the hippocampus of rats in the normal group were clearly stained, arranged neatly, with regular morphology, and uniform cell gaps. Compared with the normal group, the neurons in the CA1 region of the hippocampus of rats in the model group were arranged disorderly, the cell nuclei were pyknosis, the number of cell layers decreased, the cell bodies were swollen, showing vacuolization, and the cell gaps became longer. Compared with the model group, the neurons in the low- and high-dose groups of Huaganjian were more clearly stained, the number increased, the number of cell layers increased, and the arrangement tended to be neat. See Figure 3 .

[0051] In summary, a rat model of depression was established by combining chronic unpredictable stimulation with solitary rearing. After continuous intervention with the aqueous extract suspension of Huaganjian for 3 weeks, Huaganjian significantly alleviated the depressive behavior of the rats. The ELISA results showed that Huaganjian effectively alleviated the hyperactivity state of the HPA axis in the rats with depression. The results of histopathological staining showed that Huaganjian significantly and effectively improved the nerve damage in the hippocampal tissue of the rats with depression. It is indicated that Huaganjian can effectively improve the depressive-like behavior of the rats with depression, alleviate the hyperactivity state of the HPA axis, protect the hippocampal nerve damage, and thus play a role in the treatment of depression, with a definite curative effect.

[0052] The above are only the preferred embodiments of the present invention and are not used to limit the patent scope of the present invention. For those skilled in the art, various changes and modifications can be made to the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. An antidepressant traditional Chinese medicine composition, characterized in that, It is composed of the following raw materials in parts by weight: 6 g of green tangerine peel, 6 g of dried tangerine peel, 6 g of white peony root, 6 g of thunberg fritillary bulb, 4.5 g of oriental waterplantain rhizome, 4.5 g of cape jasmine fruit, and 4.5 g of moutan bark.

2. The composition according to claim 1, wherein The preparation method of the composition includes: soaking the raw materials in 6 - 10 times the amount of distilled water, decocting twice, combining the filtrates and concentrating to a suspension with a crude drug concentration of 2 - 3 g / mL.

3. The composition according to claim 1, characterized in that, The composition is used for preparing a drug for treating depression.

4. The composition according to claim 3, wherein The depression includes depressive-like behaviors with anhedonia and behavioral despair as the main symptoms.

5. The composition according to claim 1, wherein The dosage form of the composition is an oral preparation, including decoction, granule, tablet or capsule.

6. An antidepressant drug, characterized in that, It contains the traditional Chinese medicine composition described in claim 1 and pharmaceutically acceptable excipients.

7. Use of the traditional Chinese medicine composition described in claim 1 in the preparation of a drug for regulating the function of the HPA axis and repairing hippocampal neuron damage.

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