Application of Jiawei Danzhixiaoyao powder or extract of Jiawei Danzhixiaoyao powder in preparation of medicine for treating depression complicated with ulcerative colitis

Abstract

The invention belongs to the technical field of medicine research, and particularly relates to application of Jiawei Danzhixiaoyao powder or an extract thereof in preparation of a medicine for treating depression complicated with ulcerative colitis. Tests prove that the modified radix salviae miltiorrhizae and fructus gardeniae Xiaoyao powder can improve depression-like behaviors and relieve ulcerative colitis symptoms, and has a remarkable treatment effect on treatment of depression combined with ulcerative colitis.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical research technology, specifically relating to the application of a modified Danzhi Xiaoyao San or its extract in the preparation of a drug for treating depression complicated with ulcerative colitis. Background Technology

[0002] Depression is a common mental illness, affecting approximately 350 million people worldwide—meaning that on average, one in 20 people has had or currently has a depressive disorder. The lifetime prevalence of depressive disorders in most countries is between 8% and 12%. Depression is characterized by recurrent episodes, which can occur even during periods of remission. Relapses can manifest as depressed mood, loss of interest in life, fatigue, and slowed thinking, with the condition fluctuating repeatedly. The epidemiological characteristics of depression are influenced by a variety of factors, including genetic, psychological, social, and environmental factors. These factors may act alone or in combination, leading to the onset and progression of depression.

[0003] Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), a chronic, nonspecific inflammatory disease of the colon and rectum, with lesions limited to the large intestine mucosa and submucosa. The etiology of UC is not fully understood, but it is generally believed to result from the interaction of host responses to exogenous substances, genetic factors, and immune influences. The incidence and prevalence of UC are constantly rising. Studies have found a high proportion of UC patients with mental illnesses such as depression and anxiety. Gut microbiota imbalance and metabolic disorders are considered to play important roles in UC or mental disorders. Possible mechanisms underlying UC's association with depression and anxiety include changes in brain signaling and morphology, increased peripheral and intrabrain pro-inflammatory cytokines, damage to the nitric oxide pathway, changes in vagal nerve signaling, gut microbiota dysbiosis, and genetic factors. Ulcerative colitis (UC) can coexist with depression and anxiety, potentially leading to symptoms of common mental illnesses such as anxiety and depression. This is because patients communicate bidirectionally through the gut-brain axis, and the symptoms are persistent, resulting in impaired quality of life and reduced social functioning. However, the severity of this problem remains uncertain. The prevalence of anxiety and depression is high in UC patients, with up to one-third experiencing anxiety symptoms and one-quarter experiencing depression. The prevalence is also increased in patients with active UC: half of these patients meet the criteria for anxiety symptoms, and one-third meet the criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these conditions may improve the prognosis for UC patients.

[0004] Clinically, depression can exacerbate the course of ulcerative colitis; however, there are currently no drugs specifically for depression combined with ulcerative colitis. Traditional Chinese medicine (TCM) is characterized by its multi-component, multi-target nature, as well as its simplicity and affordability. Therefore, based on the characteristics of depression and ulcerative colitis, the use of TCM can address the lack of effective treatments for depression combined with ulcerative colitis.

[0005] The modified Danzhi Xiaoyao San formula uses Bupleurum to soothe the liver and relieve depression; Acorus tatarinowii and Polygala tenuifolia to eliminate phlegm, open the orifices, and promote the ascent of clear Yang to nourish the brain; Paeonia suffruticosa and Gardenia jasminoides to clear heat, eliminate dampness, cool the blood, and remove blood stasis to help descend turbidity; Mentha haplocalyx to promote dispersion and is the foundation for ascending clear Yang; Poria cocos and Atractylodes macrocephala to tonify the middle Jiao and strengthen the spleen, which is essential for descending turbidity; Angelica sinensis and Paeonia lactiflora to tonify the liver and harmonize the Ying, while continuing the ascending and descending of clear Yang; and Zingiber officinale and Glycyrrhiza uralensis to harmonize the other herbs. The entire formula works synergistically to soothe the liver, relieve depression, strengthen the spleen, and harmonize the Ying, treating symptoms of liver and spleen deficiency and failure of the liver to regulate the earth element. The combined effects of these herbs are to invigorate the brain and improve intelligence, while also clearing the liver and relieving depression; they address both Qi and blood, and treat both the liver and brain, allowing clear Yang to ascend and turbid Qi to descend, thus alleviating depression. The modified Danzhi Xiaoyao San has clear antidepressant activity, but no studies have been found on its use in treating depression complicated by ulcerative colitis. Summary of the Invention

[0006] Based on the above technical problems, the present invention provides the application of modified Danzhi Xiaoyao San or its extract in the preparation of a drug for treating depression complicated with ulcerative colitis.

[0007] The specific technical solution provided by this invention is as follows: This invention provides the application of Jiawei Danzhi Xiaoyao San or its extract in the preparation of a medicament for treating depression complicated with ulcerative colitis. The Jiawei Danzhi Xiaoyao San is composed of the following raw materials in parts by weight: 10-14 parts of Bupleurum chinense, 8-11 parts of Angelica sinensis, 10-14 parts of stir-fried Paeonia lactiflora, 8-12 parts of Atractylodes macrocephala, 14-16 parts of Poria cocos, 2-4 parts of Glycyrrhiza uralensis, 10-14 parts of Paeonia suffruticosa, 10-14 parts of raw Gardenia jasminoides, 10-14 parts of Acorus tatarinowii, 10-14 parts of Polygala tenuifolia, and 5-7 parts of Mentha haplocalyx.

[0008] In a preferred embodiment of the present invention, the extract is prepared according to the following steps: Weigh the medicinal materials according to the specified weight proportions, mix them, soak them in water, decoct them, collect the decoction, concentrate it, and dry it to obtain the final product.

[0009] More preferably, the step of soaking and then decocting involves adding water equivalent to 8 to 10 times the total weight of the medicinal materials, soaking for 1 hour, and then decocting 2 to 3 times, each time for 30 minutes.

[0010] More preferably, the concentration is carried out at 40 ℃ to 50 ℃.

[0011] More preferably, the drying is freeze-drying, and the extract is freeze-dried powder.

[0012] This invention provides a drug for treating depression complicated with ulcerative colitis, which uses the extract or the blood-entering component of the modified Danzhi Xiaoyao San as the active ingredient.

[0013] As a preferred embodiment of the present invention, the blood components are Salsalate, (+)-2-Phenyllacticacid, 3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoic acid, 5-(Phenylsulfonyl)-2-thiophenecarboxylic acid, Dehydrologanin, FA 18:2+2o, 1,3,7-Trimethyluric acid, 6-Deoxy-.alpha.-L-mannopyranosyl-(1->3)-[.beta.-D-glucopyranosyl-(1->6)]-1-O-(3,27-dihydroxy-27,28-dioxolup-20(29)-en-28-yl)-.beta.-D-glucopyranose, D-Mannitol 1-phosphate, cis-Pinonic acid, Azelaic acid, 2-Hydroxy-5-sulfonicotinicacid, [3-Me-His2]TRH, Aldosterone, Coumaric acid, 9-Oxo-10(E),12(E)-octadecadienoic acid, 6-{[4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)anilino]carbonyl}-3,4-dimethyl-3-cyclohexene-1-carboxylic acid, Homogentisic acid, Deoxyribose, Deoxycholic acid, Isomaltose, 12(S)-HHT, Diethyl 3,4-dihydroxy-2,5-difuroate, N-Choloylglycine, (9E,11Z)-8-Hydroxyoctadeca-9,11-dienoic acid、N-Acetyl-L-tyrosine、Octyl gallate、Daidzein 4'-sulfate、Hippuric acid、Methyl 4-formyl-3-hydroxy-2-naphthoate、Preleptospermone、2-Isopropylmalic acid、4-Formyl-2-hydroxybenzoic acid、Acetylsyringic acid、Ethyl gallate、Baicalin、5,7-Dihydroxy-2-(4-hydroxyphenyl)-3-[3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-8-yl]chroman-4-one、5'-Methylthioinosine、Paeoniflorin、Estrone-3-glucuronide、Amastatin、Benzenepropanoic acid, 4-hydroxy-、Liguiritigenin-7-O-beta-D-apiosyl-4'-O-beta-D-glucoside、Olivetol、{[3-Ethoxy-2-(ethoxycarbonyl)-3-oxo-1-propenyl]amino}acetic acid、3-Hydroxybenzoic acid、[(3R,4S,8S,8aS)-3-Hydroxy-6,8a-dimethyl-8-[(Z)-2-methylbut-2-enoyl]oxy-3-propan-2-yl-1,2,3a,4,5,8-hexahydroazulen-4-yl] 4-hydroxybenzoate、5-Fluoroindazole-3-carboxylic acid、Genipin 1-gentiobioside、3-Methoxygallic acid、Quinate、(2-Butoxyethoxy)aceticacid、Naringenin-4'-O-.beta.-D-glucuronide、Entecavir、3-Methoxytyrosine、Licoricesaponin h2、2-Oxocyclohexanepropanoic acid、5-Chloro-2,4-dihydroxy-6-methyl-3-[(2E,4E)-3-methyl-5-(1,2,6-trimethyl-5-oxocyclohex-3-en-1-yl)penta-2,4-dienyl]benzaldehyde、4-Methoxysalicylic acid、Hydrocinnamic acid, o-hydroxy-、4-Formylphenol、Vanillic acid、(3Z)-4-(Carboxymethyl)-2-(hexopyranosyloxy)-3-(2-(((2E)-3-(4-hydroxyphenyl)prop-2-enoyl)oxy)ethylidene)-3,4-dihydro-2H-pyran-5-carboxylic acid;Sulconazole、Stachydrine、3,4,5-Trimethoxy-N-(4-morpholinyl)benzamide、(r)-4-((5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-3,7-dioxohexadecahydro-1h-cyclopenta[a]phenanthren-17-yl)pentanoic acid、2-(1-Piperazinyl)acetamide、Leucine, 4-methyl-、4-Guanidinobutyric acid、Bufalin、Lenticine、5-Methyl-2-tert-butyl-2H-pyrazol-3-ylamine、1b-Hydroxycholic acid、L-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid、Glycocholate、Geniposidic acid、[1,1'-Biphenyl]-2,3',4,5',6-pentol、5?-cholanic acid-3?-ol-7_12-dione、N-Cyclohexyl-N'-(6-methyl-2-pyridinyl)thiourea、Azepindole、2,2'-Dimethoxybenzoin、5-(2',4-dihydroxy-6-keto-1',1',4'a,6'-tetramethyl-spiro[3,8-dihydrofur[2,3-e]isoindole-2,5'-decalin]-7-yl)valeric acid、Shanziside methyl ester、4-Chlorophenylsulfinylacetic acid、Ticlopidine、Echinulin、Asiatic acid、Brefeldin C、4-Benzyl-N-propylpiperazine-1-carboxamide、7-Keto-3.alpha.,12-.alpha.-dihydroxycholanic acid、Isopropyl 4-hydroxybenzoate、CD 3254、Oxadixyl、.alpha.-CEHC、4-Keto-4-[3-methyl-5-(5,6,7-trihydroxy-1,2,4a,5-tetramethyldecalin-1-yl)pentoxy]butyric acid、JasminosideA、.beta.-Homotyrosine、Dihydrocitrinone、Paeoniflorin、4-Methylumbelliferylphosphate、5-Bromo-4-hexylpyrimidine、7-Dehydroestradiol、L-Arginine, methylester、Liquiritigenin、(+)-.gamma.-Tocopherol、3,23-Dihydroxy-1-oxo-12-oleanen-28-oic acid、Asp-Ile-Arg、Salicyl glucuronide、Indacaterol、Callosumin、Ncgc00180030-03!1-(2,4,5-trimethoxyphenyl)propane-1,2-diol、Viridiflorine、Austdiol、Enterolactone、Gibepyrone D、Naringenin-4'-O-.beta.-D-glucuronide、1,3-Benzodioxole, 4,5-dimethoxy-6-(1-propen-1-yl)-、Methyl 4-coumarate、ZINC100060148、Homogentisic acid、Galangin-5,7-dimethyl ether, N-[2-(4-Mesylpiperazino)ethyl]-N'-(p-tolyl)oxamide, Butacaine, 4-Fluoro-N-[2-(4-morpholinyl)ethyl]benzamide. ,

[0014] In a preferred embodiment of the present invention, the drug further includes pharmaceutically acceptable excipients.

[0015] More preferably, the drug is an oral preparation.

[0016] More preferably, the drug is in the form of granules, syrup, tablets, or capsules.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention is the first to discover that the modified Danzhi Xiaoyao Powder has a significant effect in treating depression complicated with ulcerative colitis, specifically in the following aspects: (1) Significantly improves depressive-like behavior: A mouse model of depression combined with ulcerative colitis established by chronic restraint stress combined with low-dose DSS was demonstrated that the modified Danzhi Xiaoyao San significantly increased the number of spontaneous activities in mice and reduced the immobility time in the tail suspension test, indicating that it has a good antidepressant effect and is better than the original Danzhi Xiaoyao San.

[0018] (2) Effectively relieves symptoms of ulcerative colitis: Jiawei Danzhi Xiaoyao San can significantly improve symptoms such as weight loss and colon shortening in mice, and reduce the disease activity index ( P <0.01), reducing pathological damage to colon tissue and promoting intestinal mucosal repair, indicating that it has a clear therapeutic effect on ulcerative colitis.

[0019] (3) Clear components and clear mechanism of action: This invention identified the blood-entering components of Jiawei Danzhi Xiaoyao San by UHPLC-HRMS, clarifying the material basis of its in vivo action, and providing a scientific basis for subsequent drug development and mechanism of action research. Attached Figure Description

[0020] Figure 1 The effects of restraint modeling on mouse behavior are: A: Sugar water preference rate; B: Number of times the mouse entered the central region during OFT; C: Total distance during OFT; D: Central distance during OFT; E: Time to immobility during TST.

[0021] Figure 2 This describes the effects of DSS modeling on depressed mice. A: Weight change; B: DAI index change.

[0022] Figure 3This describes the effect of MYXS on depressive-like behavior in mice. A: Center distance at OFT; B: Total distance at OFT; C: Time to immobility (TST); D: Representative activity trajectories for each group at OFT.

[0023] Figure 4 This describes the effect of MXYS on colitis in mice. A: Weight change graph; B: DAI index change graph; C: Representative colon image; D: Colon length of animals in each group on day 42; E: Representative H&E stained colon tissue section.

[0024] Figure 5 BPC overlap spectra of each group of samples in positive ion mode.

[0025] Figure 6 BPC overlap spectra of each group of samples under negative ion mode.

[0026] Figure 7 The percentage of all identified compounds in each chemical category.

[0027] Figure 8 The percentage of compounds entering the bloodstream in each chemical category. Detailed Implementation

[0028] The following examples are provided to better understand the present invention. Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the experimental materials used in the following examples were purchased from conventional biochemical reagent stores.

[0029] The modified Danzhi Xiaoyao Powder of this invention is composed of the following ingredients by weight: 10-14 parts of Bupleurum chinense, 8-11 parts of Angelica sinensis, 10-14 parts of stir-fried Paeonia lactiflora, 8-12 parts of Atractylodes macrocephala, 14-16 parts of Poria cocos, 2-4 parts of Glycyrrhiza uralensis, 10-14 parts of Paeonia suffruticosa, 10-14 parts of raw Gardenia jasminoides, 10-14 parts of Acorus tatarinowii, 10-14 parts of Polygala tenuifolia, and 5-7 parts of Mentha haplocalyx.

[0030] The following experiment used the following formula of Jiawei Danzhi Xiaoyao San: Bupleurum chinense (230801) 12 g, Angelica sinensis (G01230507-16) 10 g, stir-fried Paeonia lactiflora (2310220) 12 g, stir-fried Atractylodes macrocephala (230801) 10 g, Poria cocos (D23070601) 15 g, Glycyrrhiza uralensis (230301) 3 g, Paeonia suffruticosa (22121714) 12 g, Gardenia jasminoides (22102109) 12 g, Acorus tatarinowii (231001) 12 g, Polygala tenuifolia (20221101) 12 g, Mentha haplocalyx (230101) 6 g (weighed separately). This formula is only for the purpose of illustrating the effect of Jiawei Danzhi Xiaoyao San in relieving / treating depression complicated with ulcerative colitis, and is not a specific limitation of Jiawei Danzhi Xiaoyao San.

[0031] 1. Establishing a mouse model of depression combined with ulcerative colitis by chronic restraint stress combined with low-dose DSS. Chronic restraint stress: Restraint for 4 hours daily for four weeks, followed by evaluation of the model using a sucrose preference test and behavioral tests. Low-dose DSS-induced UC: Evaluation model of body weight change and DAI index after 8 consecutive days of 1.5% DSS administration. Thirty-two male C57 mice aged 6-8 weeks were housed in groups of four. After one week of acclimatization, baseline sucrose levels were measured three times to exclude animals with abnormal sucrose intake. The mice were randomly divided into a control group (n=8) and a model group (n=24). The control group received normal food and water, while the model group underwent chronic restraint. Four weeks later, sucrose and behavioral tests were performed to evaluate the success of the depression model. The 24 mice in the model group that successfully developed the depression model were given 1.5% DSS to induce ulcerative colitis. The mice were observed daily, and their weight, stool consistency, and fecal blood were measured.

[0032] 2. Preparation of lyophilized powder 2.1 Composition of Clinical Prescriptions The modified Danzhi Xiaoyao San is a formula based on the long-term clinical experience of Professor Xu Erping, a famous traditional Chinese medicine doctor in Henan Province. It is prepared by adding Acorus tatarinowii and Polygala tenuifolia to Danzhi Xiaoyao San. The ingredients of the modified Danzhi Xiaoyao San are: Bupleurum chinense (230801) 12 g, Angelica sinensis (G01230507-16) 10 g, stir-fried Paeonia lactiflora (2310220) 12 g, stir-fried Atractylodes macrocephala (230801) 10 g, Poria cocos (D23070601) 15 g, Glycyrrhiza uralensis (230301) 3 g, Paeonia suffruticosa (22121714) 12 g, Gardenia jasminoides (22102109) 12 g, Acorus tatarinowii (231001) 12 g, Polygala tenuifolia (20221101) 12 g, and Mentha haplocalyx (230101) 6 g (weighed separately).

[0033] 2.2 Preparation of lyophilized powder First, soak each medicinal herb according to the above clinical prescription in grams for one hour, using 10 times the amount of water as the total weight of the herbs. After boiling for 30 minutes, filter the liquid through a sieve (180 mesh), leaving the herbs in the pot. Then, add 8 times the amount of water (approximately 6 times the total weight of the raw herbs; adjust the water amount as needed to fully soak the herbs) and boil for another 30 minutes. Add the mint during the last 5 minutes of the second decoction. Filter the second decoction through a sieve and discard the dregs. Combine the two decoctions and concentrate them in a rotary evaporator (40℃~50℃). Filter the concentrated liquid through a sieve 2-3 times, dispense into disposable plastic cups, filling each cup to 60 ml, and freeze overnight at -80℃. Freeze-drying process: Place the pre-frozen sample on a rack, cover it, start the machine, and observe the machine until the sample is completely freeze-dried, yielding 25%.

[0034] 3. Experimental Grouping After receiving 1.5% DSS stimulation, body weight and disease activity index were used as core indicators to determine the success of establishing a depression-ulcerative colitis model. Mice were randomly divided into a model group (labeled DSS), a modified Danzhi Xiaoyao San group (labeled MXYS), and a Danzhi Xiaoyao San group (labeled DZXYS). All mice were administered the drugs by gavage for one week. The normal control group and the chronic restraint stimulation combined with low-concentration DSS model group were administered an equal volume of water by gavage. The modified Danzhi Xiaoyao San and Danzhi Xiaoyao San were administered at twice the clinical dose. Behavioral evaluations were performed after the last administration. Blood was collected from the eyeballs, brain tissue was collected to separate the hippocampus, and colon tissue was collected for measurement and photography. The colon of the mice was then cut into several 0.5cm segments from the same location. Some segments were rapidly frozen in liquid nitrogen, and others were stored in 4% paraformaldehyde for later use.

[0035] 4. Animal behavioral research ① Sugar water preference experiment Before the experiment, mice were trained to consume 1% sucrose solution. They were given two bottles of sucrose solution for 12 hours, then one bottle was replaced with pure water for 12 hours. In the actual experiment, the animals were given two bottles of water, one containing 1% sucrose solution and the other pure water. After 12 hours, the bottles were collected, fluid consumption was recorded, and the sucrose solution preference ratio was calculated. Sucrose solution preference ratio (%) = [Sucrose solution intake / (Sucrose solution intake + Pure water intake)] × 100%.

[0036] ② Tail Suspension Test The mouse tail was fixed to the top of the test chamber with tape, and the mouse behavior was recorded for 6 minutes using mouse behavior video recording and analysis software. The immobility time of the mouse in the last 4 minutes was calculated.

[0037] ③Open field experiment The spontaneous behavior of animals under unstimulated conditions was observed to assess their activity level. Mice were placed one by one in the center of an open field box, and their spontaneous activities over 5 minutes were recorded using mouse behavioral video recording and analysis software, including the number of activities and the distance traveled.

[0038] 5. Pathological observation HE staining: Immerse sections sequentially in xylene for 10 min; xylene for 10 min; absolute ethanol for 5 min; absolute ethanol for 15 min; 95% ethanol for 5 min; 90% ethanol for 5 min; 80% ethanol for 5 min; 70% ethanol for 5 min; wash with distilled water. Stain sections with Harris hematoxylin for 3-8 min, then wash with tap water. Stain sections with eosin for 1-3 min, then wash with tap water. Dehydrate and clear sections sequentially in 95% ethanol for 5 min; 95% ethanol for 25 min; absolute ethanol for 15 min; absolute ethanol for 25 min; xylene for 15 min; xylene for 25 min. Remove sections from xylene and allow to air dry slightly. Mount with neutral resin. Examine under a microscope and acquire and analyze images.

[0039] 6. Analysis of the chemical composition and blood-entry components of Jiawei Danzhi Xiaoyao San 6.1 Rat serum was collected from the abdominal aorta. SPF-grade male SD rats, weighing (280±10) g, were randomly divided into a control group (n=8) and a Jiawei Danzhi Xiaoyao San group (n=8). The control group received physiological saline, while the Jiawei Danzhi Xiaoyao San group received twice the clinical dose, i.e., 24 g / kg, administered via gavage at a rate of 1 mL / 100g. Rats were weighed daily at 8:00 AM, and the gavage dose was adjusted according to body weight, continuing for 2 weeks. Rats were fasted for 12 hours prior to the last gavage administration, but water was permitted. One hour after the last gavage, blood was collected from the abdominal aorta. Blood samples were allowed to stand at room temperature for at least 30 minutes, then centrifuged at 3000 r / min for 10 minutes to thoroughly remove red blood cells, and the supernatant was collected.

[0040] 6.2 Identification of the chemical components of Jiawei Danzhi Xiaoyao San entering the bloodstream by UHPLC-HRMS First, through extensive literature review and consultation of relevant online databases, the chemical components of each medicinal herb were summarized. Information such as the molecular formula, molecular weight, structural formula, fragment ions, and source medicinal material of each chemical component was compiled into tables, thus establishing a chemical component database specific to Jiawei Danzhi Xiaoyao San. Second, the chemical component information in the database was matched with the mass spectrometry data of Jiawei Danzhi Xiaoyao San extract to obtain in vitro chemical component information. Then, based on the clear in vitro chemical components, guided by serum pharmacochemistry theory, the prototype components entering the bloodstream were identified. The in vitro chemical component database was matched with the mass spectrometry data of the serum of treated rats to characterize the prototype components entering the bloodstream. Finally, high-performance liquid chromatography-tandem triple quadrupole mass spectrometry was used to determine the content of the prototype components entering the bloodstream in the in vitro Jiawei Danzhi Xiaoyao San extract.

[0041] 7. Results 7.1 Validation of depressive behavior in model mice In a mouse model of ulcerative colitis complicated with depression, mice in the model group exhibited significant depressive-like behavior. Figure 1 Compared with the control group, mice in the chronic restraint group showed a significantly reduced preference for sucrose. P <0.01 indicates that CUMS mice exhibit depressive-like behavior. Compared with the normal group, the tail suspension immobility time of mice in the model group was significantly increased ( P <0.01, the model group mice had significantly reduced distance in the central area of ​​the open field and total movement distance ( P <0.01). In addition, the weight of chronically restrained mice was significantly reduced.

[0042] 7.2 Validation of colitis symptoms in model mice In a mouse model of ulcerative colitis complicated with depression, mice in the model group showed obvious symptoms of colitis. Figure 2 Compared with the control group, the model group mice showed significant weight loss, significantly increased disease activity index, and obvious symptoms such as bloody stools and diarrhea.

[0043] 7.3. The modified Danzhi Xiaoyao San improves depressive-like behaviors and is more effective than the modified Danzhi Xiaoyao San. The modified Danzhi Xiaoyao San group significantly increased the number of spontaneous activities in mice. P The result (<0.005) indicates that Jiawei Danzhi Xiaoyao San has a significant antidepressant effect, as shown in the following figure. Figure 3 .

[0044] 7.4. The modified Danzhi Xiaoyao Powder improves ulcerative colitis and is more effective than the modified Danzhi Xiaoyao Powder. The modified Danzhi Xiaoyao San significantly improved weight loss and colon length in mice, reduced the disease activity index (P<0.001), improved colonic tissue pathological damage in mice, and had a therapeutic effect on ulcerative colitis. Furthermore, its effect was superior to that of Danzhi Xiaoyao San. (See details...) Figure 4 .

[0045] 7.5 Analysis of Blood-Entering Components of Jiawei Danzhi Xiaoyao San This experiment used UHPLC-HRMS to collect data from blank control group samples, drug treatment group samples, blank control + traditional Chinese medicine samples, and traditional Chinese medicine samples, and compared their positive and negative ion BPC chromatograms. Figures 5-6 As shown in the spectrum, it is clear from the spectrum that there are significant differences between the traditional Chinese medicine sample and the biological sample, and there are certain differences between the spectrum of the treatment group and the blank control group.

[0046] Further classification and identification of compounds in the Jiawei Danzhi Xiaoyao San and the drug-treated samples were performed, and the results are as follows: Figures 7-8 As shown. By Figure 8The main blood components of Jiawei Danzhi Xiaoyao San are Salsalate, (+)-2-Phenyllacticacid, 3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoic acid, 5-(Phenylsulfonyl)-2-thiophenecarboxylic acid, Dehydrologanin, FA 18:2+2o, 1,3,7-Trimethyluric acid, 6-Deoxy-.alpha.-L-mannopyranosyl-(1->3)-[.beta.-D-glucopyranosyl-(1->6)]-1-O-(3,27-dihydroxy-27,28-dioxolup-20(29)-en-28-yl)-.beta.-D-glucopyranose, D-Mannitol 1-phosphate, cis-Pinonic acid, Azelaic acid, 2-Hydroxy-5-sulfonicotinicacid, [3-Me-His2]TRH, Aldosterone, Coumaric acid, 9-Oxo-10(E),12(E)-octadecadienoic acid, 6-{[4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)anilino]carbonyl}-3,4-dimethyl-3-cyclohexene-1-carboxylic acid, Homogentisic acid, Deoxyribose, Deoxycholic acid, Isomaltose, 12(S)-HHT, Diethyl 3,4-dihydroxy-2,5-difuroate, N-Choloylglycine, (9E,11Z)-8-Hydroxyoctadeca-9,11-dienoic acid、N-Acetyl-L-tyrosine、Octyl gallate、Daidzein 4'-sulfate、Hippuric acid、Methyl 4-formyl-3-hydroxy-2-naphthoate、Preleptospermone、2-Isopropylmalic acid、4-Formyl-2-hydroxybenzoic acid、Acetylsyringic acid、Ethyl gallate、Baicalin、5,7-Dihydroxy-2-(4-hydroxyphenyl)-3-[3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-8-yl]chroman-4-one、5'-Methylthioinosine、Paeoniflorin、Estrone-3-glucuronide、Amastatin、Benzenepropanoic acid, 4-hydroxy-、Liguiritigenin-7-O-beta-D-apiosyl-4'-O-beta-D-glucoside、Olivetol、{[3-Ethoxy-2-(ethoxycarbonyl)-3-oxo-1-propenyl]amino}acetic acid、3-Hydroxybenzoic acid、[(3R,4S,8S,8aS)-3-Hydroxy-6,8a-dimethyl-8-[(Z)-2-methylbut-2-enoyl]oxy-3-propan-2-yl-1,2,3a,4,5,8-hexahydroazulen-4-yl]4-hydroxybenzoate、5-Fluoroindazole-3-carboxylic acid、Genipin 1-gentiobioside、3-Methoxygallic acid、Quinate、(2-Butoxyethoxy)aceticacid、Naringenin-4'-O-.beta.-D-glucuronide、Entecavir、3-Methoxytyrosine、Licoricesaponin h2、2-Oxocyclohexanepropanoic acid、5-Chloro-2,4-dihydroxy-6-methyl-3-[(2E,4E)-3-methyl-5-(1,2,6-trimethyl-5-oxocyclohex-3-en-1-yl)penta-2,4-dienyl]benzaldehyde、4-Methoxysalicylic acid、Hydrocinnamic acid, o-hydroxy-、4-Formylphenol、Vanillic acid、(3Z)-4-(Carboxymethyl)-2-(hexopyranosyloxy)-3-(2-(((2E)-3-(4-hydroxyphenyl)prop-2-enoyl)oxy)ethylidene)-3,4-dihydro-2H-pyran-5-carboxylic acid;Sulconazole、Stachydrine、3,4,5-Trimethoxy-N-(4-morpholinyl)benzamide、(r)-4-((5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-3,7-dioxohexadecahydro-1h-cyclopenta[a]phenanthren-17-yl)pentanoic acid、2-(1-Piperazinyl)acetamide、Leucine, 4-methyl-、4-Guanidinobutyric acid、Bufalin、Lenticine、5-Methyl-2-tert-butyl-2H-pyrazol-3-ylamine、1b-Hydroxycholic acid、L-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid、Glycocholate、Geniposidic acid、[1,1'-Biphenyl]-2,3',4,5',6-pentol、5?-cholanic acid-3?-ol-7_12-dione、N-Cyclohexyl-N'-(6-methyl-2-pyridinyl)thiourea、Azepindole、2,2'-Dimethoxybenzoin、5-(2',4-dihydroxy-6-keto-1',1',4'a,6'-tetramethyl-spiro[3,8-dihydrofur[2,3-e]isoindole-2,5'-decalin]-7-yl)valeric acid、Shanziside methyl ester、4-Chlorophenylsulfinylacetic acid、Ticlopidine、Echinulin、Asiatic acid、Brefeldin C、4-Benzyl-N-propylpiperazine-1-carboxamide、7-Keto-3.alpha.,12-.alpha.-dihydroxycholanic acid、Isopropyl 4-hydroxybenzoate、CD 3254、Oxadixyl、.alpha.-CEHC、4-Keto-4-[3-methyl-5-(5,6,7-trihydroxy-1,2,4a,5-tetramethyldecalin-1-yl)pentoxy]butyric acid、JasminosideA、.beta.-Homotyrosine、Dihydrocitrinone、Paeoniflorin、4-Methylumbelliferylphosphate、5-Bromo-4-hexylpyrimidine、7-Dehydroestradiol、L-Arginine, methylester、Liquiritigenin、(+)-.gamma.-Tocopherol、3,23-Dihydroxy-1-oxo-12-oleanen-28-oic acid、Asp-Ile-Arg、Salicyl glucuronide、Indacaterol、Callosumin、Ncgc00180030-03!1-(2,4,5-trimethoxyphenyl)propane-1,2-diol、Viridiflorine、Austdiol、Enterolactone、Gibepyrone D、Naringenin-4'-O-.beta.-D-glucuronide、1,3-Benzodioxole, 4,5-dimethoxy-6-(1-propen-1-yl)-、Methyl 4-coumarate、ZINC100060148、Homogentisic acid、Galangin-5,7-dimethyl ether, N-[2-(4-Mesylpiperazino)ethyl]-N'-(p-tolyl)oxamide, Butacaine, 4-Fluoro-N-[2-(4-morpholinyl)ethyl]benzamide. ,

[0047] Unless otherwise specifically stated, the numerical values ​​set forth in these embodiments do not limit the scope of the invention. In all examples shown and described herein, any specific value should be interpreted as merely exemplary and not as a limitation, unless otherwise specified; therefore, other examples of exemplary embodiments may have different values.

Claims

1. The use of a modified Danzhi Xiaoyao San or its extract in the preparation of a medicament for treating depression complicated with ulcerative colitis, characterized in that, The modified Danzhi Xiaoyao Powder is composed of the following ingredients by weight: 10-14 parts of Bupleurum chinense, 8-11 parts of Angelica sinensis, 10-14 parts of stir-fried Paeonia lactiflora, 8-12 parts of Atractylodes macrocephala, 14-16 parts of Poria cocos, 2-4 parts of Glycyrrhiza uralensis, 10-14 parts of Paeonia suffruticosa, 10-14 parts of raw Gardenia jasminoides, 10-14 parts of Acorus tatarinowii, 10-14 parts of Polygala tenuifolia, and 5-7 parts of Mentha haplocalyx.

2. The application according to claim 1, characterized in that, The extract was prepared according to the following steps: Weigh the medicinal materials according to the specified weight proportions, mix them, soak them in water, decoct them, collect the decoction, concentrate it, and dry it to obtain the final product.

3. The application according to claim 2, characterized in that, The process of soaking and then decocting involves adding water equivalent to 8 to 10 times the total weight of the medicinal materials, soaking for 1 hour, and then decocting 2 to 3 times, each time for 30 minutes.

4. The application according to claim 2, characterized in that, The concentration was carried out at 40 ℃~50 ℃.

5. The application according to claim 2, characterized in that, The drying process is freeze-drying, and the extract is a freeze-dried powder.

6. A drug for treating depression complicated with ulcerative colitis, characterized in that, It uses the extract described in claim 1 or the blood-inducing component of the modified Danzhi Xiaoyao San as its active ingredient.

7. The drug according to claim 6, characterized in that, The blood components are Salsalate, (+)-2-Phenyllactic acid, 3-(3,4-dihydroxy-5-methoxyphenyl)prop-2-enoic acid, 5-(Phenylsulfonyl)-2-thiophenecarboxylic acid, Dehydrologanin, FA 18:2+2o, 1,3,7-Trimethyluric acid, 6-Deoxy-.alpha.-L-mannopyranosyl-(1->3)-[.beta.-D-glucopyranosyl-(1->6)]-1-O-(3,27-dihydroxy-27,28-dioxolup-20(29)-en-28-yl)-.beta.-D-glucopyranose, D-Mannitol 1-phosphate, cis-Pinonic acid, Azelaic acid, 2-Hydroxy-5-sulfonicotinic acid, [3-Me-His2] TRH, Aldosterone, Coumaric acid, 9-Oxo-10(E),12(E)-octadecadienoic acid, 6-{[4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)anilino]carbonyl}-3,4-dimethyl-3-cyclohexene-1-carboxylic acid, Homogentisic acid, Deoxyribose, Deoxycholic acid, Isomaltose, 12(S)-HHT, Diethyl3,4-dihydroxy-2,5-difuroate, N-Choloylglycine, (9E,11Z)-8-Hydroxyoctadeca-9,11-dienoic acid, N-Acetyl-L-tyrosine, Octyl gallate, Daidzein 4'-sulfate, Hippuricacid, Methyl 4-formyl-3-hydroxy-2-naphthoate, Preleptospermone, 2-Isopropylmalicacid, 4-Formyl-2-hydroxybenzoic acid, Acetylsyringic acid, Ethyl gallate, Baicalin, 5,7-Dihydroxy-2-(4-hydroxyphenyl)-3-[3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-8-yl]chroman-4-one、5'-Methylthioinosine、Paeoniflorin、Estrone-3-glucuronide、Amastatin、Benzenepropanoic acid, 4-hydroxy-、Liguiritigenin-7-O-beta-D-apiosyl-4'-O-beta-D-glucoside、Olivetol、{[3-Ethoxy-2-(ethoxycarbonyl)-3-oxo-1-propenyl]amino}acetic acid、3-Hydroxybenzoic acid、[(3R,4S,8S,8aS)-3-Hydroxy-6,8a-dimethyl-8-[(Z)-2-methylbut-2-enoyl]oxy-3-propan-2-yl-1,2,3a,4,5,8-hexahydroazulen-4-yl] 4-hydroxybenzoate、5-Fluoroindazole-3-carboxylic acid、Genipin 1-gentiobioside、3-Methoxygallicacid、Quinate、(2-Butoxyethoxy)acetic acid、Naringenin-4'-O-.beta.-D-glucuronide、Entecavir、3-Methoxytyrosine、Licoricesaponin h2、2-Oxocyclohexanepropanoic acid、5-Chloro-2,4-dihydroxy-6-methyl-3-[(2E,4E)-3-methyl-5-(1,2,6-trimethyl-5-oxocyclohex-3-en-1-yl)penta-2,4-dienyl]benzaldehyde、4-Methoxysalicylic acid、Hydrocinnamic acid,o-hydroxy-、4-Formylphenol、Vanillic acid、(3Z)-4-(Carboxymethyl)-2-(hexopyranosyloxy)-3-(2-(((2E)-3-(4-hydroxyphenyl)prop-2-enoyl)oxy)ethylidene)-3,4-dihydro-2H-pyran-5-carboxylic acid;Sulconazole、Stachydrine、3,4,5-Trimethoxy-N-(4-morpholinyl)benzamide、(r)-4-((5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-3,7-dioxohexadecahydro-1h-cyclopenta[a]phenanthren-17-yl)pentanoic acid、2-(1-Piperazinyl)acetamide、Leucine, 4-methyl-、4-Guanidinobutyric acid、Bufalin、Lenticine、5-Methyl-2-tert-butyl-2H-pyrazol-3-ylamine、1b-Hydroxycholic acid、L-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid、Glycocholate、Geniposidicacid、[1,1'-Biphenyl]-2,3',4,5',6-pentol、5?-cholanic acid-3?-ol-7_12-dione、N-Cyclohexyl-N'-(6-methyl-2-pyridinyl)thiourea、Azepindole、2,2'-Dimethoxybenzoin、5-(2',4-dihydroxy-6-keto-1',1',4'a,6'-tetramethyl-spiro[3,8-dihydrofur[2,3-e]isoindole-2,5'-decalin]-7-yl)valeric acid、Shanziside methylester、4-Chlorophenylsulfinylacetic acid、Ticlopidine、Echinulin、Asiatic acid、Brefeldin C、4-Benzyl-N-propylpiperazine-1-carboxamide、7-Keto-3.alpha.,12-.alpha.-dihydroxycholanic acid、Isopropyl 4-hydroxybenzoate、CD 3254、Oxadixyl、.alpha.-CEHC、4-Keto-4-[3-methyl-5-(5,6,7-trihydroxy-1,2,4a,5-tetramethyldecalin-1-yl)pentoxy]butyric acid、Jasminoside A、.beta.-Homotyrosine、Dihydrocitrinone、Paeoniflorin、4-Methylumbelliferyl phosphate、5-Bromo-4-hexylpyrimidine、7-Dehydroestradiol、L-Arginine, methyl ester、Liquiritigenin、(+)-.gamma.-Tocopherol、3,23-Dihydroxy-1-oxo-12-oleanen-28-oicacid、Asp-Ile-Arg、Salicyl glucuronide、Indacaterol、Callosumin、Ncgc00180030-03!1-(2,4,5-trimethoxyphenyl)propane-1,2-diol、Viridiflorine、Austdiol、Enterolactone、Gibepyrone D、Naringenin-4'-O-.beta.-D-glucuronide、1,3-Benzodioxole, 4,5-dimethoxy-6-(1-propen-1-yl)-、Methyl 4-coumarate、ZINC100060148、Homogentisic acid、Galangin-5,7-dimethyl ether、N-[2-(4-Mesylpiperazino)ethyl]-N'-(p-tolyl)oxamide、Butacaine、4-Fluoro-N-[2-(4-morpholinyl)ethyl]benzamide。, 8. The medicament according to claim 6, wherein the medicament further comprises pharmaceutically acceptable excipients.

9. The medicament according to claim 8, wherein the medicament is an oral preparation.

10. The medicament according to claim 9, wherein the medicament is in the form of granules, syrup, tablets or capsules.

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