Traditional Chinese medicine composition for treating hashimoto thyroiditis related depression anxiety disorder and application

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition for treating hashimoto thyroiditis related depression anxiety disorder and application. The traditional Chinese medicine composition comprises astragalus membranaceus, radix pseudostellariae, bighead atractylodes rhizome, pericarpium citri reticulatae, selfheal, thunberg fritillary bulb, oyster, rhizoma cyperi, angelica sinensis, radix bupleuri and liquorice. The traditional Chinese medicine composition can effectively improve the thyroid lymphocyte infiltration degree and the overall inflammatory response level of AIT mice, effectively reduce the number of depression behaviors of the mice and relieve the depression anxiety state. According to the traditional Chinese medicine composition disclosed by the invention, the effects of all the medicines generate a synergistic effect and can be prepared into a traditional Chinese medicine preparation, so that depression and anxiety disorders related to hashimoto thyroiditis can be effectively treated.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicines, and in particular relates to a traditional Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis and uses thereof. Background Art

[0002] Hashimoto's thyroiditis, also known as chronic lymphocytic or autoimmune thyroiditis, is a typical organ-specific autoimmune disease characterized by increased thyroid volume, lymphocyte infiltration of the parenchyma, and the presence of thyroid antigen-specific antibodies. Characterized by thyroid-specific autoantibodies, it is not only the most common thyroid autoimmune disease, but also the most common autoimmune disease to date. The incidence of HT has risen rapidly over the past 30 years. 0.3-1.5 cases per 1,000 people. More than 10% of women are antibody-positive, and about 2% of women have clinical manifestations, and the incidence increases with age; although the exact cause has not yet been fully elucidated, Hashimoto's thyroiditis is associated with the interaction between genetic factors, environmental factors, and epigenetic influences. Therefore, reducing the incidence of Hashimoto's thyroiditis and improving the quality of life of patients are urgent issues to be addressed.

[0003] The symptoms and signs associated with Hashimoto's thyroiditis have always been considered to be caused by hypothyroidism, including anxiety, depression and other emotional disorders during the disease process. In recent years, studies have pointed out that patients with Hashimoto's thyroiditis are susceptible to anxiety and depression disorders, and Hashimoto's thyroiditis patients have more obvious anxiety and depression than normal people. The emotional state of patients with Hashimoto's thyroiditis may be the result of the combined influence of multiple factors such as thyroid function antibodies and nodules. In terms of incidence, the prevalence of anxiety and depression disorders in patients with Hashimoto's thyroiditis is higher than that in the general population.

[0004] In traditional Chinese medicine, HT can be classified as "goiter" and "goiter". Its main location is the thyroid gland in front of the neck, which is closely related to the liver and spleen. Deficiency of spleen qi is the root cause, and local phlegm and blood stasis in the thyroid gland is the symptom. It is a syndrome of deficiency of the root cause and excess of the symptom. Its onset is inseparable from improper diet, improper water and soil, emotional injury and physical factors. With the change of modern lifestyle, the pressure of life increases, and the harm caused by emotional factors becomes more and more obvious. "Revised Yan's Jisheng Prescriptions: Treatment of Goiter" says, "Goiters are mostly caused by uncontrolled joy and anger, excessive worry... Qi stagnation and blood stasis, goiters and tumors." Joy and anger, emotional stagnation, liver failure to dredge, spleen failure to move, water and moisture transportation is not good, and phlegm is gathered; liver qi stagnation and blood vessels are blocked, which can also lead to poor circulation of qi and blood, qi stagnation, phlegm stagnation and blood stasis in front of the neck to form goiters. It can be seen from this that emotional distress is an important cause of the disease, "liver depression and spleen deficiency" is the core pathogenesis of the disease, and goiter is caused by qi stagnation and phlegm stagnation.

[0005] In view of the above pathogenesis, the inventors found that although Chinese medicine has a certain understanding of HT and a certain number of prescriptions have been used clinically, the traditional Chinese medicine treatment of thyroid in the past mainly focused on "soothing the liver and regulating qi", and there is no Chinese patent medicine for HT patients with anxiety and depression. As the course of HT is prolonged, the symptoms manifested in the later stage are characterized by insufficient vital energy and deficiency of yang energy, such as fatigue, edema, fear of cold, constipation, etc. The inventors believe that at this time, in addition to soothing the liver, Chinese medicine for strengthening the spleen and replenishing qi should be used to replenish vital energy, protect the spleen and stomach, and replenish yang energy. Yang energy promotes blood circulation, and the stagnant phlegm can be warmed, so that the phlegm knot will be dispersed. Summary of the invention

[0006] In view of the problems existing in the prior art, the present invention provides a Chinese medicine composition and use for treating depression and anxiety disorders associated with Hashimoto's thyroiditis. The Chinese medicine composition can significantly improve the thyroid lymphocyte infiltration level and the overall inflammatory response level of AIT mice, while effectively reducing the depressive behavior of mice and relieving the depressive and anxious state.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions.

[0008] A traditional Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis comprises the following raw materials in parts by weight: 13-17 parts of astragalus, 6-9 parts of pseudoginseng, 7-11 parts of atractylodes, 4-8 parts of tangerine peel, 10-14 parts of selfheal, 7-10 parts of thunbergia thunbergii, 9-14 parts of oyster, 6-8 parts of cyperus, 3-6 parts of angelica, 8-10 parts of bupleurum and 4-8 parts of liquorice.

[0009] Preferably, the Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts of Astragalus, 6 parts of Pseudostellariae Radix, 9 parts of Atractylodes macrocephala, 6 parts of Citrus reticulata, 12 parts of Prunella vulgaris, 10 parts of Fritillaria thunbergii, 10 parts of Oyster, 6 parts of Cyperus rotundus, 3 parts of Angelica sinensis, 10 parts of Bupleurum chinense, and 6 parts of Licorice.

[0010] Preferably, the Chinese medicine composition comprises the following raw materials in parts by weight: 13 parts of astragalus, 6 parts of pseudoginseng, 7 parts of atractylodes, 4 parts of tangerine peel, 10 parts of selfheal, 7 parts of thunbergia thunbergii, 9 parts of oyster, 6 parts of cyperus, 3 parts of angelica, 8 parts of bupleurum, and 4 parts of liquorice.

[0011] Furthermore, the pharmaceutical composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis is a preparation prepared by adding pharmaceutically acceptable excipients.

[0012] Furthermore, the preparation is an oral dosage form.

[0013] Furthermore, the oral dosage form is water pills, granules, tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, honey pills, powders, pills, solutions or plasters, etc.

[0014] Use of any of the above-mentioned Chinese medicine compositions in the preparation of a preparation for treating depression and anxiety disorders associated with Hashimoto's thyroiditis The properties, flavors, meridians and main effects of each medicinal raw material used in the present invention are as follows.

[0015] The main medicines are Astragalus and Pseudo-ginseng, as follows.

[0016] Astragalus: [Nature and flavor and meridians] Sweet, slightly warm. Enters the lung and spleen meridians. [Functions and indications] Tonifies qi and raises yang, consolidates the exterior and stops sweating, promotes diuresis and reduces swelling, promotes the production of body fluids and nourishes blood, relieves stagnation and relieves numbness, removes toxins and discharges pus, and heals sores and promotes tissue regeneration. Used for qi deficiency and fatigue, poor appetite and loose stools, sinking of qi in the middle, chronic diarrhea and prolapse of the anus, bloody stool and metrorrhagia, spontaneous sweating due to exterior deficiency, edema due to qi deficiency, internal heat and thirst, sallow complexion due to blood deficiency, hemiplegia, pain and numbness in the arthralgia, carbuncle that is difficult to heal, and carbuncle that does not heal for a long time.

[0017] Pseudostellariae Radix: [Nature and flavor and meridians] Sweet, slightly bitter, neutral. Enters the spleen and lung meridians. [Functions and indications] Replenishes qi and strengthens the spleen, produces body fluid and moistens the lungs. Used for spleen deficiency, fatigue, loss of appetite, weakness after illness, qi and yin deficiency, spontaneous sweating and thirst, dry cough due to lung dryness.

[0018] The assistant drugs are Atractylodes macrocephala, dried orange peel, Prunella vulgaris, Fritillaria thunbergii and oyster, as follows.

[0019] Atractylodes macrocephala: [Nature and flavor and meridians] Bitter, sweet, warm. Enters the spleen and stomach meridians. [Functions and indications] Strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating, and stabilizes the fetus. Used for spleen deficiency, poor appetite, abdominal distension and diarrhea, phlegm and fluid, dizziness and palpitations, edema, spontaneous sweating, and restless fetuses.

[0020] Tangerine peel: [Nature and flavor and meridians] Bitter, pungent, warm. Enters the lung and spleen meridians. [Functions and indications] Regulates qi and strengthens the spleen, dries dampness and resolves phlegm. Used for abdominal distension, loss of appetite, vomiting and diarrhea, cough with excessive phlegm.

[0021] Prunella Vulgaris: [Nature and flavor and meridians] Pungent, bitter, cold. Enters the liver and gallbladder meridians. [Functions and indications] Clears the liver and purges fire, improves eyesight, disperses stagnation and reduces swelling. Used for red and swollen eyes, night pain in the eyeballs, headache and dizziness, scrofula, goiter, breast abscess, breast lumps, and breast pain.

[0022] Fritillaria thunbergii: [Nature and flavor and meridians] Bitter, cold. Enters the lung and heart meridians. [Functions and indications] Clears away heat, resolves phlegm and relieves cough, detoxifies, disperses stagnation and eliminates carbuncle. Used for wind-heat cough, phlegm-fire cough, lung carbuncle, breast carbuncle, scrofula, and sores.

[0023] Oyster: [Nature and flavor and meridians] Salty, slightly cold. Enters the liver, gallbladder, and kidney meridians. [Functions and indications] Tranquilizes the mind, subdues yang and replenishes yin, softens and disperses lumps. Used for palpitations, insomnia, dizziness, tinnitus, scrofula, phlegm, masses, and lumps. Calcined oysters are astringent, acid-reducing and analgesic. Used for spontaneous sweating, night sweats, spermatorrhea, metrorrhagia, leukorrhea, stomachache and acid regurgitation.

[0024] The adjuvant drugs are Cyperus rotundus, Angelica sinensis and Bupleurum chinense, as follows.

[0025] Cyperus rotundus: [Nature and flavor and meridians] Pungent, slightly bitter, slightly sweet, neutral. Enters the liver, spleen, and triple burner meridians. [Functions and indications] Soothes the liver and relieves depression, regulates qi and relieves fullness, regulates menstruation and relieves pain. Used for liver depression and qi stagnation, chest and flank pain, hernia pain, breast pain, spleen and stomach qi stagnation, abdominal distension, fullness and pain, irregular menstruation, amenorrhea and dysmenorrhea.

[0026] Angelica: [Nature and flavor and meridians] Sweet, pungent, warm. Enters the liver, heart, and spleen meridians. [Functions and indications] Nourishes blood and promotes blood circulation, regulates menstruation and relieves pain, moistens the intestines and promotes bowel movements. Used for blood deficiency and sallow complexion, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, asthenic abdominal pain, rheumatic arthralgia, injuries from falls, carbuncles, ulcers, and constipation caused by dry intestines. Wine Angelica promotes blood circulation and promotes menstruation. Used for amenorrhea and dysmenorrhea, rheumatic arthralgia, and injuries from falls.

[0027] Bupleurum: [Nature and flavor and meridians] Pungent, bitter, slightly cold. Enters the liver, gallbladder, and lung meridians. [Functions and indications] Disperses and reduces fever, relieves liver qi and depression, and raises Yang Qi. Used for colds and fever, alternating cold and heat, chest and flank pain, irregular menstruation, uterine prolapse, and rectal prolapse.

[0028] The adjuvant drug is licorice, as follows.

[0029] Licorice: [Nature and flavor and meridians] Sweet, neutral. Enters the heart, lung, spleen, and stomach meridians. [Functions and indications] Tonifies the spleen and replenishes qi, clears away heat and detoxifies, removes phlegm and relieves cough, relieves pain, and harmonizes various medicines. Used for spleen and stomach weakness, fatigue, palpitations and shortness of breath, cough with sputum, abdominal and limb cramps and pain, carbuncle, sore and ulcer, and relieves drug toxicity and potency.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0031] The invention is based on the theory of traditional Chinese medicine, has a rigorous formula, and has a clear relationship between monarch, minister, assistant and envoy: in the formula, astragalus and Pseudostellaria are monarchs; Atractylodes macrocephala, dried orange peel, Prunella vulgaris, Fritillaria thunbergii and oyster are ministers; Cyperus rotundus, Angelica sinensis and Bupleurum are assistants; and Licorice is the envoy; the medicines are carefully selected, and it has a comprehensive regulatory effect of multiple targets, multiple links and multiple levels, and can improve the thyroid lymphocyte infiltration degree and the overall inflammatory response level of AIT mice, and at the same time effectively reduce the depressive and anxiety behaviors related to AIT mice, and relieve the depressive and anxiety state. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Visualization images of each group of trajectories.

[0033] Figure 2 Effects of each group on pathological changes of thyroid tissue in AIT mice.

[0034] Figure 3Effects of each group on the expression levels of NLRP3, ASC, Caspase 1, GSDMD, and IL-1β proteins in the thyroid tissue of AIT mice (A. NG group; B. MG group; C. medication group 1; D. medication group 2; E. medication group 3; F. SeG group). DETAILED DESCRIPTION

[0035] The present invention is further described below by specific examples, and the present invention is not limited to the following examples. Within the scope of the present invention or without departing from the content, spirit and scope of the present invention, the changes, combinations or substitutions made to the present invention are obvious to those skilled in the art and are included in the scope of the present invention.

[0036] Example 1.

[0037] A traditional Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis is prepared from the following medicinal raw materials in the following weight proportions: 15 parts of astragalus, 6 parts of pseudostellaria, 9 parts of atractylodes, 6 parts of tangerine peel, 12 parts of selfheal, 10 parts of thunbergia thunbergii, 10 parts of oyster, 6 parts of cyperus rotundus, 3 parts of angelica, 10 parts of bupleurum, and 6 parts of liquorice.

[0038] A method for preparing a Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis: Put oyster, astragalus, herbaceous earth, bupleurum and licorice tablets into a container. Add 8 times the total weight of the herbs in cold water, making sure the water covers the herbs by 2 to 3 cm; soak for 30 minutes to fully soak the herbs. After boiling over high heat, switch to low heat and continue to decoct for 30 minutes; filter out the liquid after the first decoction for the second decoction, add the remaining herbs and 6 times the total weight of the herbs in warm water, making sure the water just covers the herbs; after soaking for 30 minutes, boil over high heat, and then decoct over low heat for 20 minutes; after the decoction is completed, combine the two decoctions, filter out the residue, and obtain a Chinese medicine decoction.

[0039] Example 2.

[0040] In order to investigate the efficacy of the prescription of the present invention and the prescription reported in the literature, an experimental autoimmune thyroiditis animal model was designed, and a comparative study was conducted by detecting the specific antibody titer level, thyroid hormone level and cytokine secretion level in the animal serum to investigate the therapeutic effect of the traditional Chinese medicine composition of the present invention on AIT mouse-related depression and anxiety disorders.

[0041] Experimental Animals: NOD.H-2 h4Sixty mice were purchased from Jackson Laboratory, strain number No. 004447, animal certificate number 2211A01937, and bred and raised in the SPF-level laboratory of the Experimental Animal Center of Liaoning University of Traditional Chinese Medicine, license number SYXK (Liao) 2019-0004. This experiment was approved by the Ethics Committee of Liaoning University of Traditional Chinese Medicine, ethics review number 21000042021128.

[0042] drug: Sodium iodide was purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd., and the Chinese medicine composition was purchased from the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine. The crude drug mass concentration was 1.0 g / mL. The Chinese medicines used in this study all met the requirements of the 2020 edition of the Pharmacopoeia of the People's Republic of China. Positive control drug: Selenium yeast tablets, chemical drugs, 50 μg / tablet, purchased from Mudanjiang Lingtai Pharmaceutical Co., Ltd., national medicine standard H10940161, suspension concentration was 1.625 μg / mL.

[0043] Main reagents and instruments: Mouse anti-thyroglobulin antibody (TGAb), mouse anti-thyroid peroxidase antibody (TPOAb) ELISA kits (ELISA, catalog number: ml037680, ml002215); Hematoxylin-eosin (HE) staining kit (Biyuntian Biotechnology Co., Ltd., batch number: C0105), NLRP3 antibody (Beijing Bioson Biotechnology Co., Ltd., batch number: BA12271673), ASC antibody (Jiangsu Qinke Biological Research Center Co., Ltd., batch number: #10w2797), Caspase 1 antibody (Wuhan Sanying Biotechnology Co., Ltd., batch number: 00112731), GSDMD-N antibody (Jiangsu Qinke Biological Research Center Co., Ltd., batch number: #2437), IL-1β antibody (Wuhan Sanying Biotechnology Co., Ltd., batch number: 00106096) GAPDH (Wuhan Sanying Biotechnology Co., Ltd., batch number: 10029187), and primers were designed and synthesized by Beijing Qingke Biotechnology Co., Ltd.

[0044] Thermo ST16R high-speed refrigerated centrifuge (Thermo Corporation, USA); Arcadia tissue embedding machine, Biocut slicer (Leica Corporation, Germany); infinite M200Pro microplate reader (NanoQuant Corporation, Switzerland); infiniteM200Pro microplate reader (NanoQuant Corporation, Switzerland); T100 thermal cycler (Bio Rad Thermal Cycler Corporation, USA); QuantStudio3 PCR amplification instrument (ABI Corporation, USA); Power Pac1645050 electrophoresis instrument, 1704150 membrane transfer instrument (Bio-Rad Corporation, USA); Tanon-5200 developer (Tanon Corporation, Shanghai).

[0045] Example 3.

[0046] AIT+CUMS model preparation: 60 NOD.H-2 mice were selected as the ideal animal model for AIT h4 Mice were randomly divided into control group (NG), model group (MG), drug administration groups 1-3, and positive control group, with 10 mice in each group. The modeling mice in each group were allowed to drink 0.05% sodium iodide water freely, and the mice in the control group were allowed to drink distilled water freely. At the same time, chronic unpredictable mild stress (CUMS) was performed in the 4th week. The 6 groups of mice were randomly given different stress factors every day in a random order so that the animals could not anticipate the occurrence of stimulation, including cage tilting at 45℃ overnight, wet bedding overnight, behavior restriction for 2h, cage shaking, fasting (24h), water deprivation (24h), tail clamping for 1min, and ice water swimming (4℃, 5min) stress stimulation (Table 1). The AIT+CUMS animal model was established in the 8th week.

[0047] CUMS specific operations: Behavior restriction for 2 hours: Place the mice in a 50 ml ep tube. After all mice have been manipulated, place them tail to tail in the cage with the original bedding and cover the cage. Time for 2 hours and take the mice out after 2 hours. Wet bedding overnight: Soak the bedding in the mouse cage with mouse drinking water, drain the excess water, place the mouse in the cage overnight, and replace it with dry bedding the next morning; Tilt the cage at 45°C overnight: Use something to prop up the mouse cage so that it tilts at 45° overnight, and restore the cage angle the next day; Shake the cage (5 min): remove the water and feed from the cage, and shake it irregularly for 5 min. Ice water swimming (4°C, 5 min): Take a large cage, put in 4° water to the height of the mouse standing upright, put the mouse in, so that the mouse can just touch the bottom of the cage with its feet, and then swim. After 5 minutes, take it out, wipe it dry, and put it back in the original cage; No water (24h), no food (24h): remove the water and food from the cage and put them back after 24h; Tail clamp (1 min): Clamp the mouse’s tail with a plastic clamp for 1 min and then remove it.

[0048] Table 1. Order of implementation of chronic unpredictable mild stimulation.

[0049] Example 4.

[0050] Dosage: After modeling, oral administration was started. The dosage per kg body weight (g / kg) of mice was 9.1 times that of humans. Group 1 was administered: 6.045 g·kg -1 , Group 2: 12.09 g·kg -1 , Group 3: 24.18 g·kg -1 ; Positive control drug (SeG) group: 0.0325 g·kg -1 The NG group and the MG group were gavaged with an equal amount of distilled water, the positive control drug group was gavaged with selenium yeast suspension once a day, the NG group was fed with distilled water, and the drug-treated group was gavaged with the drug prepared in Example 1. The samples were collected 8 weeks after gavage.

[0051] HE staining was used to observe the thyroid tissue structure and lymphocyte infiltration in mice: The thyroid tissues of mice in each group were fixed with 4% paraformaldehyde, dehydrated and embedded in gradients, and cut into slices of about 5 μm. The paraffin sections were dewaxed, rehydrated, stained with hematoxylin for 5 min, rinsed with tap water, differentiated with color separation solution, rinsed with tap water and blued sliced. The sections were dehydrated in alcohol and stained with eosin. After staining, the sections were dehydrated, transparentized, and sealed. Fields of view were randomly selected under a high-power microscope to observe the pathological changes of thyroid tissue.

[0052] Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of TGAb and TPOAb in mouse serum: After the last administration of the drug, mice in each group were fasted and deprived of water for 12 hours. The eyeballs of the mice were removed and blood was collected. The blood was placed in a 4°C refrigerator for 2 hours, and then centrifuged at 3000r / min and 4°C for 5 minutes. The serum was carefully separated and stored at -80°C. The serum TGAb and TPOAb levels were detected according to the instructions of the ELISA kit.

[0053] Real-time PCR was used to detect the expression of NLRP3, ASC, Caspase 1, GSDMD and IL-1β mRNA: The total RNA of thyroid tissue was extracted strictly according to the instructions of RNA extraction kit, and the purity and concentration of RNA were calculated. The genomic DNA reaction was removed by reverse transcription kit, and the reaction system was prepared on ice. After incubation at 42℃ for 2min, the reaction solution was added for reverse transcription and incubated at 42℃ for 15min and 85℃ for 5min to synthesize cDNA. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as internal reference mRNA, and SYBR Green was used for amplification in the following reaction conditions: 95℃ pre-denaturation for 30s, 95℃ denaturation for 5s, 60℃ annealing for 30s, 40 cycles, 95℃ for 15s, 60℃ for 1min, 95℃ for 15s, 50℃ for 30s, and quantitative analysis was performed according to 2-ΔΔCt method.

[0054] Western Blot was used to detect the expression of NLRP3, ASC, Caspase 1, GSDMD and IL-1β proteins: The concentration of thyroid tissue protein was determined by BCA protein quantification kit, and protein denaturation was performed with 5× loading buffer, with the loading amount of about 10 μg per well. Electrophoresis was performed at 160V for 30min, and wet transfer was performed at 100V for 30min. After transfer, the membrane was washed with TBST for 3 times, each time for 10min, blocked with 5% skim milk powder for 1.5h, washed with TBST for 4 times, each time for 10min, and the corresponding protein to be tested was added, and the primary antibody diluent was prepared and incubated at 4°C overnight; the next day, the membrane was washed with TBST for 4 times, each time for 10min, and then incubated with rabbit secondary antibody, and the secondary antibody was added and shaken on a shaker at room temperature for 1h, washed with TBST for 4 times, each time for 10min, and developed and exposed with ECL working solution in turn, and the bands were saved and the gray value was analyzed using Image J software.

[0055] Statistical analysis: SPSS 23.0 software was used for statistical analysis of data, and one-way analysis of variance was used. The measurement data were expressed as mean ± standard deviation (`x± s). P <0.05 is statistically significant.

[0056] Example 5.

[0057] Open field test: Compared with the NG group, the number of standing times, defecation times, central quadrant time, and central quadrant ratio of mice in the MG group were significantly reduced ( P <0.01); compared with the MG group, the number of standing times of mice in the 2-3 groups and the SeG group increased significantly ( P<0.01), among which group 3 had the best effect; the number of defecation, central quadrant time, and central quadrant ratio of groups 1-3 increased significantly ( P <0.05, P <0.01), the number of bowel movements, central quadrant time, and central quadrant ratio in the SeG group were not statistically significant ( P >0.01), see Table 2, Figure 1 .

[0058] Table 2 Open field test results (`x± s, n=4) Note: Compared with the control group, 1） P <0.01; compared with the model group, 2） P <0.05, 3） P <0.01.

[0059] Effects of each group on serum TGAb and TPOAb levels in AIT mice: Compared with the NG group, the levels of TGAb and TPOAb in the MG group were significantly increased ( P <0.01); compared with the MG group, the TGAb levels in the 1st to 3rd administration groups and the SeG group were significantly decreased ( P <0.01), TPOAb levels in the 2-3 groups and SeG group were significantly decreased ( P <0.01), among which group 3 had the best effect, as shown in Table 3.

[0060] Table 3 Effects of each group on the expression levels of TGAb and TPOAb in mice in each group (`x± s, n=6) Compared with NG group 1） P <0.01, compared with MG group 2） P <0.01.

[0061] Pathological observation results of thyroid tissues of AIT mice in each group: The thyroid follicular epithelial cells of mice in the NG group were intact in structure, arranged regularly, and of uniform size. The colloid was abundant in the cavity, and lymphocytes were occasionally seen. Compared with the NG group, the thyroid follicle structure of the MG group was significantly destroyed, the follicles were of different sizes, arranged in disorder, the mesenchyme was reduced, and lymphocyte infiltration was diffuse in the follicular cavity and the gap, with severe inflammation. Compared with the model group, the thyroid follicular epithelial cells of mice in drug groups 1 to 3 and SeG groups were slightly intact in structure, arranged more regularly, lymphocyte infiltration was reduced, and the inflammation was significantly alleviated. The effect of drug group 3 was the most significant, as shown in Table 1. Figure 2 .

[0062] Effects of each group on the expression levels of NLRP3, ASC, Caspase 1, GSDMD and IL-1β mRNA in thyroid tissue of AIT mice: Compared with the NG group, the mRNA expressions of NLRP3, ASC, Caspase-1, IL-1β, and GSDMD in the MG group were significantly increased ( P <0.05, P <0.01); compared with the MG group, the NLRP3 mRNA expression level in the SeG group was significantly decreased ( P <0.05), the expression level of Caspase-1 mRNA in the 2-3 groups and the SYT group was significantly decreased ( P <0.01), and the IL-1β mRNA expression levels in the drug 1-3 groups and the SeG group were decreased ( P <0.05), the expression level of GSDMD mRNA in the SeG group was significantly decreased ( P <0.01), and there was no significant difference in the reduction of GSDMD mRNA expression in groups 1 to 3 ( P >0.01), see Table 4.

[0063] Table 4 Effects of each group on the expression levels of NLRP3, ASC, Caspase 1, GSDMD and IL-1β mRNA in thyroid tissue of AIT mice Note: Compared with the control group, 1） P <0.05, 2） P <0.01; compared with the model group, 3） P <0.05, 4） P <0.01.

[0064] Effects of each group on the expression levels of NLRP3, ASC, Caspase 1, IL-1β and GSDMD proteins in thyroid tissue of AIT mice The results of this study showed that compared with the NG group, the expression of NLRP3, ASC, Caspase 1, IL-1β, and GSDMD proteins in the thyroid gland of the MG group mice was significantly increased ( P <0.01); compared with the MG group, the expression of ASC, Caspase-1, and GSDMD proteins in the thyroid tissue of mice in the 1-3 and SeG groups was significantly decreased ( P <0.01), the expression of NLRP3 protein in the drug 1 group and the SeG group was significantly decreased (P <0.01), the expression of IL-1β protein in the drug 1 group, drug 3 group and SeG group was significantly decreased ( P <0.01), and there was no significant difference in the expression of other histones ( P >0.05), see Table 5. Figure 3 .

[0065] Table 5 Effects of each group on the expression levels of NLRP3, ASC, Caspase 1, IL-1β, and GSDMD proteins in thyroid tissue of AIT mice Note: Compared with the normal group, 1） P <0.01; compared with the model group, 2） P <0.01.

[0066] In summary: Tables 1, 2 and Figure 1 , 2 The results showed that compared with NG, the number of standing times, defecation times, central quadrant time, and central quadrant ratio of mice in the MG group were significantly reduced, the TGAb and TPOAb levels were significantly increased, pathological changes occurred in the thyroid tissue, the follicular epithelial cell structure was significantly destroyed, and lymphocyte infiltration occurred, indicating that the model was successfully established. Groups 1 to 3 were administered with medication, indicating that the present invention can increase the number of standing times, defecation times, central quadrant time, and central quadrant ratio of mice, reduce the levels of TGAb and TPOAb in the serum of AIT mice, restore the structural integrity of follicular epithelial cells in the thyroid tissue of mice, reduce lymphocyte infiltration and inflammation, and improve pathological changes in thyroid tissue. The effect of group 3 was the most significant, indicating that it has comparable efficacy to first-line clinical medications. Table 3-5, Figure 3 The results of groups 1 to 3 indicated that the present invention may improve and inhibit excessive inflammatory response and autoimmunity in AIT mice by inhibiting the Caspase-1-dependent classical pyroptosis signaling pathway, and the therapeutic effect was significant, with group 3 having the best effect.

Claims

1. A Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis, characterized in that: The invention comprises the following raw materials: astragalus, atractylodes, liquorice, pseudostellaria, tangerine peel, bupleurum, angelica, thunbergii bulb, selfheal, oyster and cyperus.

2. The Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 13-17 parts of astragalus, 7-11 parts of atractylodes, 4-8 parts of liquorice, 6-9 parts of pseudostellaria, 4-8 parts of tangerine peel, 8-10 parts of bupleurum, 3-6 parts of angelica, 7-10 parts of thunbergii, 10-14 parts of selfheal, 9-14 parts of oyster and 6-8 parts of cyperus.

3. The Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis according to claim 2, characterized in that: Specifically, the raw materials are composed of the following parts by weight: 15 parts of Astragalus, 6 parts of Pseudostellariae Radix, 9 parts of Atractylodes macrocephala, 6 parts of Citrus reticulata, 12 parts of Prunella vulgaris, 10 parts of Fritillaria thunbergii, 10 parts of Oyster, 6 parts of Cyperus rotundus, 3 parts of Angelica sinensis, 10 parts of Bupleurum chinense, and 6 parts of Licorice.

4. The Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis according to claim 2, characterized in that: Specifically, the raw materials are composed of the following parts by weight: 13 parts of Astragalus, 7 parts of Atractylodes, 4 parts of Licorice, 6 parts of Pseudostellariae Radix, 4 parts of Tangerine Peel, 8 parts of Bupleurum, 3 parts of Angelica, 7 parts of Fritillariae Thunbergii, 10 parts of Prunella Vulgaris, 9 parts of Oyster, and 6 parts of Cyperus rotundus.

5. A Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis, characterized in that: The invention comprises the Chinese medicine composition according to any one of claims 1 to 4 and pharmaceutically acceptable excipients.

6. The Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis according to any one of claims 1 to 4, characterized in that: The Chinese medicine composition is in the form of an oral dosage form.

7. The Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis according to claim 6, characterized in that: The oral dosage form is water pill, granule, tablet, film-coated tablet, enteric-coated tablet, capsule, hard capsule, soft capsule, oral liquid, honey pill, powder, pill, solution or plaster.

8. Use of the traditional Chinese medicine composition for treating depression and anxiety disorders associated with Hashimoto's thyroiditis as claimed in any one of claims 1 to 4 in the preparation of a drug for treating depression and anxiety disorders associated with Hashimoto's thyroiditis.

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