Traditional Chinese medicine composition for improving cognition, emotion, memory and depression state as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for improving cognition, emotion, memory and depression states and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following components in parts by mass: radix scutellariae, rhizoma coptidis, radix puerariae, rhizoma anemarrhenae, bitter gourd, rhizoma zingiberis, stiff silkworm, American ginseng and radix notoginseng. Wherein the radix scutellariae and the rhizoma coptidis are monarch drugs and mainly attack the core pathogenesis; the radix puerariae, the rhizoma anemarrhenae and the pseudo-ginseng serve as ministerial drugs, assist monarch drugs and treat secondary pathogenesis; bitter gourd, rhizoma zingiberis, stiff silkworm and American ginseng are used as adjuvant drugs to regulate drug properties and treat and treat both symptoms and root causes; and radix puerariae and pseudo-ginseng are used as conductant drugs for guiding channels or harmonizing the drugs. The traditional Chinese medicine composition disclosed by the invention can be used for preventing and treating cognitive disorder, mood disorder and depressive state caused by metabolic disorder. The traditional Chinese medicine composition is small in side effect, high in individuation and suitable for being taken for a long time, and has an obvious treatment effect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine, and particularly relates to a traditional Chinese medicine composition for improving cognition, emotion, memory and depression state, and a preparation method and application thereof. BACKGROUND

[0002] Depression, also known as depressive disorder, is characterized by persistent low mood, loss of interest and pleasure, and a variety of physical and psychological symptoms, which seriously affects the daily life, work, study and interpersonal relationships of patients, and brings great pain to patients, and even can lead to suicide. There is a complex and close relationship between depression and cognitive dysfunction. Depression can cause impairment of multiple dimensions of cognitive function, such as attention and memory. Cognitive dysfunction itself can exacerbate the symptoms of depression, affect the treatment and prognosis of depression. Depression is usually associated with central nervous system reward function disorder.

[0003] Dopamine is an important neurotransmitter in the brain, mainly responsible for regulating emotion, motivation, motor control, cognitive function and endocrine system. It participates in reward mechanism, attention concentration, learning and memory by activating different receptors, and can be used to treat shock, Parkinson's disease and other diseases as a drug. Studies have reported that energy surplus caused by high-energy density diet (HEDD) can stimulate dopamine release, leading to down-regulation of DA receptors (such as D2R). Animal models show that long-term energy surplus stimulates dopamine release, leading to reduced dopamine responsiveness in the nucleus accumbens (NAc) of mice, which is similar to drug addiction or tolerance phenomenon. Reduced dopamine responsiveness can trigger "reward deficiency syndrome" (RDS), prompting individuals to compensate for the lack of pleasure by increasing food intake, ultimately leading to dopamine signal disorder, accompanied by metabolic disorders and neuroinflammation, causing emotional disorders, cognitive impairment, memory loss, and depression.

[0004] High-fat high-sugar diet is the most common high-energy density diet in today's society, and continuous energy intake exceeding body consumption leads to fat accumulation and metabolic abnormalities. Its core manifestations are weight gain, dyslipidemia, elevated blood glucose, etc., and are closely related to diseases such as obesity and metabolic syndrome, causing metabolic disorder diseases. Studies have shown that patients with metabolic disorders have a significantly higher risk of depression than the general population, and depression can also exacerbate the development of metabolic disorders. Therefore, it is very important to strengthen the research of drugs for treating depression.

[0005] At present, the main drug for treating depression is western medicine, and tricyclic antidepressants are still commonly used drugs, such as amitriptyline, imipramine, doxepin, clomipramine (chloropromazine) and the like. Due to the adverse reactions of antidepressants, the drugs cannot fully exert the curative effect, and the treatment effect is poor, the treatment course is long, and the treatment effect is poor. SUMMARY

[0006] The present application aims to provide a traditional Chinese medicine composition, a preparation method, a medicine and an application. The traditional Chinese medicine composition can prevent and treat cognitive impairment, emotional disorder, enhance memory, and depression caused by metabolic disorders, and provides a new safe and effective drug for the treatment of depression caused by metabolic disorders.

[0007] In order to solve the above technical problems, the present application provides the following technical solutions:

[0008] The present application provides a traditional Chinese medicine composition, which comprises, by mass fraction: 42-48 parts of Huangqi, 42-48 parts of Huanglian, 57-63 parts of Gegen, 57-63 parts of Zhimu, 42-48 parts of Kugua, 12-18 parts of Ganjiang, 13-17 parts of Jiangcan, 7-11 parts of Xiyangshen and 2-4 parts of Sanqi.

[0009] Preferably, by mass fraction, it comprises: 45 parts of Huangqi, 45 parts of Huanglian, 60 parts of Gegen, 60 parts of Zhimu, 45 parts of Kugua, 15 parts of Ganjiang, 15 parts of Jiangcan, 9 parts of Xiyangshen and 3 parts of Sanqi.

[0010] The present application provides a preparation method of the traditional Chinese medicine composition described in the above technical solutions, which comprises: mixing the Huangqi, Huanglian, Gegen, Zhimu, Kugua, Ganjiang, Jiangcan, Xiyangshen and Sanqi, and then performing water extraction and alcohol precipitation to obtain the traditional Chinese medicine composition.

[0011] Preferably, in terms of the mixture of the Huangqi, Huanglian, Gegen, Zhimu, Kugua, Ganjiang, Jiangcan, Xiyangshen and Sanqi, the mass-volume ratio of the mixture and water during the water extraction is 1g:8-12mL; and the number of water extraction is 2-3 times.

[0012] Preferably, the water extraction method comprises: boiling the mixture and water, and then continuously boiling for 90-120min, to obtain a first filtrate and a filter residue; mixing the filter residue with water again, boiling and then continuously boiling for 90-120min to obtain a second filtrate; and the amount of water added in the two times is the same.

[0013] Preferably, after obtaining the second filtrate, it comprises: mixing the first filtrate and the second filtrate, and then concentrating.

[0014] Preferably, the concentrated solution is subjected to alcohol precipitation; the alcohol precipitation is performed for 22-26 hours; and the concentrated solution is mixed with anhydrous ethanol to obtain a mixture, and the volume concentration of the anhydrous ethanol in the mixture is 38%-42%.

[0015] Preferably, after the alcohol precipitation, the alcohol precipitation solution is subjected to filtration, concentration and drying in sequence.

[0016] The application provides application of the traditional Chinese medicine composition prepared by the preparation method in the above technical solution in preparation of a medicine for preventing and / or treating at least one of the following diseases,

[0017] 1) cognitive impairment caused by metabolic disorders;

[0018] 2) emotional disorders caused by metabolic disorders;

[0019] 3) memory decline caused by metabolic disorders;

[0020] 4) depressive state caused by metabolic disorders.

[0021] The application provides a medicine for preventing and / or treating diseases, which comprises a traditional Chinese medicine component and a pharmaceutically acceptable adjuvant; the traditional Chinese medicine component is the traditional Chinese medicine composition prepared by the preparation method in the above technical solution or any one of the above technical solutions; and the diseases are one or more than two of cognitive impairment caused by metabolic disorders, emotional disorders caused by metabolic disorders, memory decline caused by metabolic disorders and depressive state caused by metabolic disorders.

[0022] The application provides a traditional Chinese medicine composition, a preparation method, a medicine and application. From the perspective of traditional Chinese medicine, the core pathogenesis of depression is internal retention of damp-heat, stagnation of liver-QI, deficiency of both QI and YIN and blood stasis blocking collaterals. The traditional Chinese medicine composition of the application comprises Huangqi, Huanglian, Gegen, Zhimu, Kugua, Ganjiang, Jiangcan, Xiyangshen and Sanqi, which are matched around the core pathogenesis to achieve the effects of clearing heat and removing dampness, soothing liver and relieving depression, tonifying QI and YIN and activating blood and dredging collaterals, so as to treat depression. Huangqi and Huanglian in the traditional Chinese medicine composition are the monarch drugs, which mainly attack the core pathogenesis; Gegen, Zhimu and Sanqi are the minister drugs, which assist the monarch drugs and treat the secondary pathogenesis; and Kugua, Ganjiang, Jiangcan and Xiyangshen are the auxiliary drugs, which adjust the drug properties and treat the secondary symptoms.

[0023] The traditional Chinese medicine composition of the application can treat depression caused by metabolic disorders and relieve cognitive impairment and emotional disorders of depression. The application proves that the traditional Chinese medicine composition has the effect of treating depression caused by energy excess through mouse experiments. The application uses Chinese traditional compound instead of conventional drug treatment, has small side effects, is strong in individualization, is suitable for long-term taking and has obvious therapeutic effect. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 This is a schematic diagram illustrating the preparation of the traditional Chinese medicine compound used in Example 1;

[0025] Figure 2 The results of changes in depressive symptoms in each group in Example 2;

[0026] Figure 3 The results show the behavioral changes in each group of mice in Example 2;

[0027] Figure 4 The results of behavioral changes in each group in Example 2;

[0028] Figure 5 The results of Nissl body staining of neurons in the hippocampus region of the central nervous system of mice in each group in Example 2;

[0029] Figure 6 The results of Nissl body staining of prefrontal cortex neurons in the central nervous system of mice in each group of Example 2 are shown. Detailed Implementation

[0030] This invention provides a traditional Chinese medicine composition, comprising, by weight: 42-48 parts of Scutellaria baicalensis, 42-48 parts of Coptis chinensis, 57-63 parts of Pueraria lobata, 57-63 parts of Anemarrhena asphodeloides, 42-48 parts of bitter melon, 12-18 parts of dried ginger, 13-17 parts of Bombyx mori, 7-11 parts of American ginseng, and 2-4 parts of Panax notoginseng.

[0031] The composition provided by this invention comprises 42-48 parts by weight, preferably 43-46 parts, and most preferably 45 parts of Scutellaria baicalensis. In this invention, Scutellaria baicalensis exerts the effects of clearing heat and drying dampness, purging fire and detoxifying in this composition, especially effective in clearing damp-heat in the middle and upper jiao, and can also clear heart fire to regulate emotions and improve depression.

[0032] Based on the mass fraction of Scutellaria baicalensis, the composition provided by this invention includes 42-48 parts of Coptis chinensis, more preferably 44-46 parts, and more preferably 45 parts. In this invention, the Coptis chinensis primarily clears damp-heat in the middle jiao (spleen, stomach, and large intestine), and also purges excess fire in the heart and stomach; by clearing and purging stagnant fire in the liver and gallbladder, it can indirectly regulate qi to alleviate liver stagnation and fire syndrome.

[0033] Based on the mass fraction of Scutellaria baicalensis, the composition provided by this invention includes 57-63 parts of Pueraria lobata, more preferably 59-62 parts, and more preferably 60 parts. In this invention, Pueraria lobata has the effects of promoting body fluid production and quenching thirst, invigorating the spleen and stomach's clear yang, improving dry mouth and fatigue in diabetes, and simultaneously invigorating yang and soothing the liver to relieve depression.

[0034] Based on the mass fraction of Scutellaria baicalensis, the composition provided by this invention includes 57-63 parts of Anemarrhena asphodeloides, more preferably 58-61 parts, and more preferably 60 parts. In this invention, Anemarrhena asphodeloides has the effects of nourishing yin and moistening dryness, counteracting the yin-damaging effects of Coptis chinensis and Scutellaria baicalensis (which are bitter and cold), and clearing deficiency heat to calm the mind.

[0035] The composition provided by the present application comprises 42-48 parts of bitter gourd, which can be 43-46 parts, and more preferably 45 parts, based on the mass parts of Huangqi.

[0036] The composition provided by the present application comprises 12-18 parts of dried ginger, which can be 13-16 parts, and more preferably 15 parts, based on the mass parts of Huangqi. The dried ginger has the effects of warming middle energizer and protecting stomach, counteracting the bitter and cold of Huanglian and Huangqi, and preventing cold and cool from damaging spleen.

[0037] The composition provided by the present application comprises 13-17 parts of Jieseng, which can be 14-16 parts, and more preferably 15 parts, based on the mass parts of Huangqi. In the present application, the Jieseng has the effects of resolving phlegm and removing obstruction, calming wind and stopping convulsion, and is used for phlegm and blood stasis (such as obesity and stiff limbs), and relieving depression and resolving phlegm.

[0038] The composition provided by the present application comprises 7-11 parts of American ginseng, preferably 8-10 parts, and more preferably 9 parts, based on the mass parts of Huangqi. In the present application, the American ginseng has the effects of tonifying qi and nourishing yin, and is used for deficiency of both qi and yin, and tonifying qi to relieve liver.

[0039] The composition provided by the present application comprises 2-4 parts of Sanqi, and more preferably 3 parts, based on the mass parts of Huangqi. In the present application, the Sanqi has the effects of tonifying qi and nourishing yin, and is used for deficiency of both qi and yin, and tonifying qi to relieve liver.

[0040] In the present application, the sources of the above components are not particularly limited, and conventional products can be used.

[0041] Traditional Chinese medicine has unique advantages in treating metabolic disorders and their complications. In the theory of traditional Chinese medicine, metabolic disorders caused by energy excess and depression have similar etiology and pathogenesis, such as emotional factors, such as emotional discomfort, and physical factors, such as yin deficiency, liver and kidney yin deficiency, and functional disorders of heart, liver, spleen and kidney, and abnormal factors of qi and blood, such as fluid deficiency and blood stasis.

[0042] High pressure life, high oil and high salt diet, etc. can cause metabolic disorders of the body, and is easy to cause central nervous system and depression related to nervous system disorders. The traditional Chinese medicine compound preparation has the effects of benefiting qi and activating blood, removing blood stasis and dredging collaterals. The present application adopts high-fat high-sugar simulated high energy density diet, combined with streptozotocin (STZ) to induce energy excess state, and prepares HEDD mouse model. The HEDD mouse model is used as an example for verification, and the common acute stress restraint stress mouse model (ARS) is used as a model control. It is found that during the high energy density diet, the mice will show progressive depression. After the treatment of the traditional Chinese medicine composition, the depression-like behavior of the HEDD mouse model is recovered well, which fully shows the potential effect of the traditional Chinese medicine compound preparation in treating cognitive impairment, emotional disorder, memory decline and depression caused by metabolic disorders.

[0043] The present application also provides a preparation method of the traditional Chinese medicine composition, comprising: mixing the radix scrophulariae, the rhizoma coptidis, the radix puerariae, the rhizoma anemarrhenae, the momordica charantia, the zingiber officinale, the silkworm chrysalis, the panax quinquefolium and the notoginseng, and then performing water extraction and alcohol precipitation to obtain the traditional Chinese medicine composition.

[0044] As an optional embodiment, the present application performs water extraction on the mixture of the radix scrophulariae, the rhizoma coptidis, the radix puerariae, the rhizoma anemarrhenae, the momordica charantia, the zingiber officinale, the silkworm chrysalis, the panax quinquefolium and the notoginseng after mixing with water. The method of water extraction comprises: boiling the mixture and water, and then continuously decocting for 90-120 min, more preferably for 100 min, filtering to obtain a first filtrate and a filter residue; boiling the filter residue and water again, and then continuously decocting for 90-120 min, more preferably for 100 min, to obtain a second filtrate. The mass-volume ratio of the mixture and water is 1g:8-12mL, more preferably 1g:10mL. The number of water extraction is preferably 2-3 times, more preferably 2 times. In the specific embodiment of the present application, the extraction is performed twice, and the amount of water added is the same. The present application extracts twice to ensure that the drug components in the mixture are completely extracted.

[0045] As an optional embodiment, the present application mixes the first filtrate and the second filtrate, and then performs concentration and alcohol precipitation in sequence. The present application obtains a concentrated solution after concentration, and performs alcohol precipitation on the concentrated solution. The present application concentrates to 20%-50% of the original volume of the mixture of the first filtrate and the second filtrate, preferably 25%, and the concentration is performed by heating. As an optional embodiment, the present application mixes the concentrated solution obtained by concentration and anhydrous ethanol to perform alcohol precipitation, so that the volume concentration of anhydrous ethanol in the mixed solution is 38%-42%, preferably 40%. After alcohol precipitation, the liquid phase is an alcohol precipitation solution. The time of alcohol precipitation is 22-26h, more preferably 24h. The alcohol precipitation removes impurities and enriches effective components.

[0046] As an optional embodiment, after the alcohol precipitation, the method further comprises sequentially filtering, concentrating and drying the alcohol precipitation solution. The present application does not have special limitation on the filtering mode, and a conventional mode can be used. In the specific embodiment of the present application, the filtering is performed using filter paper. The present application concentrates and dries the filtrate obtained after the filtration of the alcohol precipitation solution. The present application does not have special limitation on the concentrating mode, and a conventional method can be used. The drying mode of the present application comprises drying. The drying temperature of the present application is 55-65℃, preferably 60℃; and the drying time is 2-4h, more preferably 3h. The dried product is obtained after the drying, and the dried product is ground to obtain the compound preparation.

[0047] The present application provides the use of the traditional Chinese medicine composition in the above technical solution in the preparation of a medicine for preventing and / or treating at least one of the following diseases,

[0048] 1) cognitive impairment caused by metabolic disorder;

[0049] 2) emotional disorder caused by metabolic disorder;

[0050] 3) memory decline caused by metabolic disorder;

[0051] 4) depressive state caused by metabolic disorder.

[0052] As an optional embodiment, the depressive state of the present application comprises depression. The present application researches and finds that during the high-energy-density diet, the mice will gradually develop depression, and after the treatment of the traditional Chinese medicine compound preparation of the present application, the depressive behavior of the mice is well recovered, which fully shows the potential effect of the traditional Chinese medicine compound preparation of the present application in treating cognitive function and emotional disorder.

[0053] The present application provides a medicine for preventing and / or treating depression, comprising a traditional Chinese medicine component and a pharmaceutically acceptable adjuvant; the traditional Chinese medicine component is the traditional Chinese medicine composition in the above technical solution or the traditional Chinese medicine composition obtained by the preparation method in the above technical solution.

[0054] As an optional embodiment, the disease of the present application is one or more than two of cognitive impairment caused by metabolic disorder, emotional disorder caused by metabolic disorder, memory decline caused by metabolic disorder and depressive state caused by metabolic disorder.

[0055] The present application does not have special limitation on the pharmaceutically acceptable adjuvant, and a conventional product can be used.

[0056] As an optional embodiment, the dosage form of the medicine of the present application comprises one or more of oral dosage form, injection and suppository, and more preferably oral dosage form, injection and suppository. As an optional embodiment, the oral dosage form of the present application comprises powder. The preparation method of the powder is not particularly limited in the present application, and conventional method can be used.

[0057] In order to further illustrate the present application, the technical solutions provided by the present application are described in detail below in combination with the drawings and examples, but they should not be understood as limiting the scope of protection of the present application.

[0058] Preparation of traditional Chinese medicine compound preparation in Example 1

[0059] The traditional Chinese medicine compound is obtained by mixing and then extracting and purifying the traditional Chinese medicine, as shown in the schematic diagram Figure 1 The specific preparation method is as follows:

[0060] 1. Preparation of traditional Chinese medicine compound: mix 45g of Huangqin, 45g of Huanglian, 60g of Gegen, 60g of Zhimu, 45g of Kugua, 15g of Ganjiang, 15g of Jiangcan, 9g of Xiyangshen and 3g of Sanqi to obtain the compound raw medicine;

[0061] 2. Extraction of effective components of traditional Chinese medicine compound: add 10 times the weight of the compound raw medicine to pure water, heat and boil, then extract for 100 minutes, filter to obtain the first filtrate, add 10 times the weight of the compound raw medicine to pure water to the residue, heat and boil, then extract for 100 minutes, filter to obtain the second filtrate, mix the first filtrate and the second filtrate, and the solution is 1188mL, then concentrate to 297mL, obtain the concentrated solution, and cool the concentrated solution to room temperature.

[0062] 3. Purification and preparation of traditional Chinese medicine compound: mix the obtained concentrated solution with a certain volume of industrial alcohol to obtain a mixed solution, ensure that the mixed solution contains anhydrous ethanol with a volume concentration of 40%, i.e. mix 297mL of the concentrated solution with 198mL of anhydrous ethanol, then alcoholize for 24 hours after mixing, filter the obtained solution using gauze folded four times, then heat and concentrate the obtained filtrate, and when the concentration reaches the state of suspension, place it in a 60℃ oven to dry, then grind the obtained dried material to obtain the traditional Chinese medicine compound preparation.

[0063] Example 2

[0064] 1. Eighty 6-week-old male C57BL / 6J mice were randomly divided into three groups: a blank control group (Control, n=10), a high-energy-density diet group (HEDD, n=60), and an acute stress restraint group (ARS, n=10). After one week of acclimatization, the HEDD mice were administered streptozotocin (STZ) via intraperitoneal injection and fed a high-fat diet for four weeks to establish the HEDD model. The HEDD model is a metabolic disease comorbid with depression model.

[0065] The control group received intraperitoneal injections of saline solution, with the amount of saline solution being the same as the amount of STZ injected; the control group was fed a normal diet for 4 weeks.

[0066] The ARS group underwent pressure restraint stress for 4 hours a day for 14 consecutive days; the ARS group was simultaneously fed a normal diet for 4 weeks.

[0067] Four weeks later, the HEDD group mice underwent the open field test and tail suspension test to observe changes in the depressive manifestations of mice in each group.

[0068] On day 7 of the high-energy-density diet model, the results were as follows: Figure 2 As shown in a to f. Figure 2 In the diagram, 'a' refers to the initial experimental trajectory, 'b' represents the total distance traveled, 'c' represents the latency, 'd' represents the number of times the sample entered the central region, 'e' represents the time spent in the central region, and 'f' represents the distance traveled in the central region. Figure 2 The "anxious" in "a-f" refers to the group of HEED mice identified through cluster analysis after behavioral testing. This group exhibits excessive anxiety on day 7 of modeling, suggesting that excessive anxiety may be an early symptom of HEED. The results indicate that on day 7 of modeling, mice in the high-energy-density diet group were the first to show hyperactivity and anxiety-like symptoms.

[0069] On day 14 of the high-energy-density diet model, the results were as follows: Figure 2 As shown in g~l in the diagram. Figure 2 In the diagram, g represents the initial experimental trajectory, h represents the total distance traveled, i represents the latency, j represents the number of times the central region is entered, k represents the time spent in the central region, and l represents the distance traveled in the central region. Figure 2 The term "comorbridity" refers to the group of mice with comorbid depression identified through cluster analysis after behavioral testing during the HEDD modeling process. The results show that as the modeling time progressed and the disease developed, the cognitive and emotional behaviors of HEED mice changed, gradually changing from excessive anxiety (Anxious group) to a state of depression (comorbridity group) and finally to a HEED group without anxiety or depression.

[0070] It can be seen that at the 14th day of modeling, the mice in the high-energy density diet group showed significant depressive comorbidity, and the open field experiment showed decreased motor ability, increased latency, significantly decreased number of times entering the central area, and significantly decreased central area residence time and central area movement distance.

[0071] When the high-energy density diet lasted for 28 days, the incidence of depression in the mice in the high-energy density diet group also significantly increased. Figure 3 ). Figure 3 In the comorbridity, comorbidity refers to HEDD comorbid depression mice.

[0072] Figure 3 In the comorbridity, a refers to the open field experiment trajectory diagram, b refers to the total movement distance, c refers to the latency, d refers to the number of times entering the central area, e refers to the central residence time, f refers to the central movement distance, g refers to the tail suspension test heat map, h refers to the despair time, and i refers to the despair times.

[0073] 2. The HEDD comorbid depression mice in the high-energy density diet group were immediately randomly divided into a model group (Model, n=13), a metformin group (MET, n=5), a 0.5-fold group (SQTLW 0.5x, n=7), a 1-fold group (SQTLW 1x, n=7), a 2-fold group (SQTLW 2x, n=7), and a 4-fold group (SQTLW 4x, n=7) for treatment.

[0074] The model group, the metformin group, the 0.5-fold group, the 1-fold group, the 2-fold group, the 4-fold group, and the Control group and the ARS group in step 1 of Example 2 continued to be subjected to the following experiments. The ARS group was set up to serve as a disease control, and the depression caused by HEDD and the depression caused by ARS were similar in behavior, thereby providing better support for HEDD comorbid depression.

[0075] Among them, the mice in the 0.5-fold group, the 1-fold group, the 2-fold group, and the 4-fold group were given the traditional Chinese medicine compound preparation prepared in Example 1, and the administration mode was intragastrically administered at 10:00 every day, once a day. Among them, the mice in the 0.5-fold group were administered at a dose of 3g / kg, the mice in the 1-fold group were administered at a dose of 6g / kg, the mice in the 2-fold group were administered at a dose of 12g / kg, and the mice in the 4-fold group were administered at a dose of 24g / kg. The mice in the MET group were administered by intragastric administration at a dose of 200mg / kg. The treatment lasted for 4 weeks.

[0076] Metformin was used as a positive control because it can increase insulin sensitivity in HEED, which may be helpful in alleviating the pathological process of HEED. Antidepressants were not used, and metformin was used as a positive control because one of the side effects of antidepressants is that they can disrupt the body's energy metabolism, leading to obesity and other internal medical conditions.

[0077] The control group, model group, and ARS group were treated with saline by gavage. The treatment lasted for 4 weeks, and behavioral changes in each group were assessed using an opening field test.

[0078] The results are as follows Figure 4 As shown, Figure 4 In the diagram, 'a' refers to the initial experimental trajectory, 'b' refers to the total distance traveled, 'c' refers to the latency, 'd' refers to the number of times the central region was entered, 'e' refers to the time spent in the central region, and 'f' refers to the distance traveled in the central region.

[0079] During drug treatment, the opening experiment results showed no significant difference in total movement distance among the groups of mice. However, the latency to enter the central region was significantly increased in the model group, while this phenomenon was significantly reversed in the MET group and the 0.5-fold group. All other groups also showed varying degrees of reversal. Compared to the Control group, the number of times mice entered the central region, the time spent in the central region, and the central movement distance were significantly reduced in the HEDD and ARS groups. After treatment, this phenomenon was effectively reversed in all SQTLW groups, but not in the MET group. Furthermore, there were significant differences between the SQTLW groups and the MET group, suggesting that SQTLW has a significant advantage in treating depression comorbid with high-energy-density diets.

[0080] After treatment, mice were anesthetized, perfused with 4% paraformaldehyde, and the whole brain of the mice was harvested. After fixation for 24 hours, the tissue was dehydrated, embedded, and paraffin sections were prepared. Morphological staining was then performed according to the Nissl staining method.

[0081] The results are as follows Figures 5-6 As shown, Figure 5 In the image, Hippocampus refers to the mouse hippocampus and is shown at low magnification; CA1, CA2, CA3, and DG represent the CA1, CA2, CA3, and DG regions of the mouse hippocampus, respectively, and are shown at high magnification. Figure 6 The prefrontal cortex refers to the prefrontal cortex. Figure 6 The top row shows the morphological changes of Nissl staining in the prefrontal cortex of different groups under low magnification; the first column on the left of the vertical column shows the morphological changes of Nissl staining in the prefrontal cortex under 20x magnification; the middle and right columns of the vertical column show the morphological changes of Nissl staining in the cortical region under 40x magnification.

[0082] The function of Nissl body is to synthesize structural proteins required for updating organelles, enzymes required for synthesizing neurotransmitters, and peptide neurotransmitters. The shape, quantity and distribution of Nissl body vary with different neurons. Nissl body is particularly abundant in neurons with vigorous metabolic function. When neurons are damaged or over-fatigued, Nissl body can decrease, disintegrate or even disappear. During the recovery process of damage or fatigue, Nissl body reappears, increases and can reach the normal level. In this experiment, Nissl body of neurons is dyed and observed by using toluidine blue dyeing solution, so that normal Nissl body appears dark blue. The Nissl staining of Control group, model group (Model), MET, 0.5 times group (SQTLW 0.5x), 1 times group (SQTLW 1x), 2 times group (SQTLW 2x) and 4 times group (SQTLW 4x) mice is carried out, and the results show that the Nissl body of Control group is granular or patchy, uniformly distributed in the cytoplasm, the nuclear shape is clear (circular / ovoid), and the nucleolus can be seen; the number of Nissl body of Model group decreases, the granules are blurred or completely disappear, the cytoplasmic staining is light, and the cytoplasm changes into vacuoles, indicating that neurons are damaged; and the pyknotic and dense-stained apoptotic neurons can be observed. After drug treatment, the damage of neurons in the prefrontal lobe and hippocampus of central nervous system caused by high-energy density diet is effectively recovered, and the traditional Chinese medicine compound preparation of the application can treat mood disorders and cognitive disorders caused by metabolic disorders. The traditional Chinese medicine compound preparation of the application can treat mood disorders and cognitive disorders caused by metabolic disorders, and can also relieve depression.

[0083] In summary, through mouse experiments, the traditional Chinese medicine compound preparation prepared in the application has good improvement and treatment effects on cognitive function and mood disorders related to metabolic disorders, and the treatment effect is better than that of traditional drug metformin, and is expected to be used as a drug for treating cognitive function and mood disorders related to metabolic disorders and depression, and has good application prospect.

[0084] Although the above embodiment describes the present application in detail, it is only a part of the embodiments of the present application, not all the embodiments, and other embodiments can be obtained according to the present embodiment without creativity, which all belong to the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition, characterized in that, By weight, it includes: Scutellaria baicalensis 42-48 parts, Coptis chinensis 42-48 parts, Pueraria lobata 57-63 parts, Anemarrhena asphodeloides 57-63 parts, Bitter melon 42-48 parts, dried ginger 12-18 parts, Bombyx mori 13-17 parts, American ginseng 7-11 parts, and Panax notoginseng 2-4 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, By weight, it includes: 45 parts Scutellaria baicalensis, 45 parts Coptis chinensis, 60 parts Pueraria lobata, 60 parts Anemarrhena asphodeloides, 45 parts Bitter melon, 15 parts dried ginger, 15 parts Bombyx mori, 9 parts American ginseng, and 3 parts Panax notoginseng.

3. The preparation method of the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, include: The Scutellaria baicalensis, Coptis chinensis, Pueraria lobata, Anemarrhena asphodeloides, Trichosanthes kirilowii, Zingiber officinale, Bombyx mori, Panax notoginseng, and Panax notoginseng were mixed and then subjected to water extraction and alcohol precipitation to obtain a traditional Chinese medicine composition.

4. The preparation method according to claim 3, characterized in that, Based on the mixture of Scutellaria baicalensis, Coptis chinensis, Pueraria lobata, Anemarrhena asphodeloides, Momordica charantia, Zingiber officinale, Bombyx mori, Panax quinquefolius, and Panax notoginseng, the mass-to-volume ratio of the mixture to water during the water extraction is 1g:8-12mL; and the number of water extractions is 2-3.

5. The preparation method according to claim 4, characterized in that, The water extraction method includes: boiling the mixture and water and then continuing to boil for 90-120 minutes, filtering to obtain a first filtrate and a filter residue; mixing the filter residue with water again, boiling and then continuing to boil for 90-120 minutes to obtain a second filtrate; the amount of water added in both cases is the same.

6. The preparation method according to claim 5, characterized in that, After obtaining the second filtrate, the process includes: mixing the first filtrate and the second filtrate and then concentrating them.

7. The preparation method according to claim 6, characterized in that, The concentrated solution is then subjected to alcohol precipitation for 22-26 hours. During the alcohol precipitation, the concentrated solution is mixed with anhydrous ethanol to achieve a volume concentration of 38%-42% of anhydrous ethanol in the mixture.

8. The preparation method according to claim 3 or 7, characterized in that, The process after alcohol precipitation also includes: sequentially filtering, concentrating, and drying the alcohol precipitate.

9. The use of the traditional Chinese medicine composition according to claim 1 or 2, or the traditional Chinese medicine composition obtained by the preparation method according to any one of claims 3 to 8, in the preparation of a medicament for the prevention and / or treatment of at least one of the following diseases: 1) Cognitive impairment caused by metabolic disorders; 2) Mood disorders caused by metabolic disorders; 3) Memory decline caused by metabolic disorders; 4) Depressive state caused by metabolic disorders.

10. A medicament for preventing and / or treating a disease, characterized by, It includes traditional Chinese medicine components and pharmaceutically acceptable excipients; the traditional Chinese medicine components are the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition obtained by the preparation method according to any one of claims 3 to 8; the disease is one or more of the following: cognitive impairment caused by metabolic disorder, mood disorder caused by metabolic disorder, memory loss caused by metabolic disorder, and depressive state caused by metabolic disorder.

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