A traditional Chinese medicine composition for treating coronary heart disease depression and application and preparation method thereof

Abstract

This invention discloses a traditional Chinese medicine composition for treating coronary heart disease and depression, its application, and preparation method. The traditional Chinese medicine composition comprises the following components by weight: 10-15 parts of Salvia miltiorrhiza; 8-12 parts of Panax ginseng; 8-12 parts of Ligusticum chuanxiong; 8-12 parts of Trichosanthes kirilowii; 8-12 parts of Paeonia lactiflora; 6-10 parts of Cyperus rotundus; 6-10 parts of Curcuma longa; 8-12 parts of Acanthopanax senticosus; 6-10 parts of Morinda officinalis; and 4-8 parts of Cinnamomum cassia. The preparation method includes: (1) Weighing each Chinese medicinal material according to the proportion of Chinese medicine, cleaning and crushing it appropriately; (2) First decoction: Add 3 times the weight of drinking water to the medicinal material, soak for 30 minutes, then heat to boiling, turn to low heat and keep boiling, continue to decoct for 30 minutes, filter and collect the filtrate; (3) Second decoction: Add 3 times the weight of drinking water to the dregs again, heat to boiling in the same way, turn to low heat and decoct for 30 minutes, filter and collect the filtrate; (4) Combine the filtrates obtained in steps (2) and (3), heat and concentrate them over low heat, and finally make a medicinal liquid with a total volume of 100 mL.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a traditional Chinese medicine composition for treating coronary heart disease and depression, its application, and preparation method. Background Technology

[0002] Coronary atherosclerotic heart disease (CAD) is one of the most common cardiovascular diseases worldwide, with high morbidity and mortality rates, severely impacting patients' quality of life and survival. Studies have found a high incidence of depression in CAD patients and those undergoing PCI, and a significant mutually reinforcing relationship exists between CAD and depression: patients with depression have a 2-3 times higher risk of developing CAD than the general population, and approximately one-third of CAD patients experience depressive symptoms. It is evident that depression not only damages patients' mental health but may also exacerbate physical symptoms, reduce treatment adherence, increase the risk of adverse cardiovascular events, and thus worsen clinical prognosis. Therefore, CAD complicated by (and after) depression (CAD-related depression) has become a common disease seriously threatening public health. Currently, it is believed that CAD imposes a heavy economic burden and enormous mental stress on patients. Coupled with external factors such as a faster pace of life and increased social pressure, many CAD patients often experience negative emotions such as anxiety and depression. Furthermore, the longer the duration of CAD, the higher the risk of comorbid depression. Depression can cause patients to be in a state of high stress for a long time, promoting excessive activation of the autonomic nervous system, accelerating intimal damage, promoting the formation of atherosclerotic plaques, and aggravating the condition, thus affecting the prognosis of coronary heart disease. Clinical studies have shown that in patients with coronary heart disease and depression, the degree of depression (HAMA, HAMD scores) is significantly positively correlated with the degree of coronary artery stenosis (Gensini score). Currently, the clinical treatment of patients with coronary heart disease and depression mainly involves giving antidepressants on top of routine coronary heart disease treatment. Therefore, the treatment plan is mechanically separated. That is, although coronary heart disease drugs (such as nitroglycerin, beta-blockers, etc.) combined with antidepressants (such as fluoxetine) can partially relieve the symptoms of coronary heart disease and depression in a short period of time, there are risks of drug interactions, significant cardiovascular side effects, poor patient compliance, and a series of adverse reactions (such as severe gastrointestinal reactions, excessive sedation, etc.), thus affecting the prognosis.

[0003] Currently, Traditional Chinese Medicine (TCM) treatment for coronary heart disease complicated with anxiety / depression has advantages such as good treatment compliance, high safety, and significant clinical efficacy. TCM categorizes coronary heart disease under the terms "chest pain" or "heart pain," while depression falls under the categories of "depression" or "lily disease," both sharing a common pathological basis. Their pathogenesis is inseparable from the command of the "heart." The heart, as a visceral organ, governs blood vessels, forming the material basis of the heart; the heart, as a spiritual organ, governs consciousness, forming the superstructure of the heart. Therefore, the pathogenesis belongs to the category of visceral heart disease caused by dysfunction of the heart's function of governing blood vessels, and spiritual heart disease caused by dysfunction of the heart's function of governing consciousness. The disease nature is characterized by deficiency of the root and excess of the branch, with deficiency of Qi, blood, Yin, and Yang as the root, and Qi stagnation, blood stasis, phlegm-fire, and dampness obstruction as the branch. The pathogenesis of this disease lies in the prolonged chest pain and heart pain, leading to stagnation of Qi and disharmony of blood vessels, which in turn affects the heart's function of "governing the mind." External stimuli, such as fear and anxiety stemming from the awareness of the dangers of coronary heart disease, further exacerbate emotional distress. These two factors combined affect the patient's emotions, leading to the onset of the disease. Furthermore, emotional distress causes Qi stagnation, which over time generates heat, disturbs the mind, depletes vital energy, and impairs blood circulation, resulting in Qi deficiency and blood stasis, further contributing to the development of depression associated with coronary heart disease. Thus, the symptoms of cardiac dysfunction in this disease can further increase the patient's psychological burden, creating a vicious cycle. The "Expert Consensus on the Diagnosis and Treatment of Dual-Heart Diseases Using Integrated Traditional Chinese and Western Medicine" points out that the main symptoms of depression in coronary heart disease are Qi stagnation, blood stasis, phlegm turbidity, and deficiency of vital energy. When emotions are imbalanced and out of balance, Qi becomes disordered, and blood stagnates along with Qi stagnation, leading to various complications over time.

[0004] Therefore, current clinical treatment of coronary heart disease complicated with anxiety and depression mainly revolves around treating both the heart and liver, focusing on methods such as soothing the liver, regulating qi, promoting blood circulation, resolving phlegm, and relieving depression, while also calming the mind. The main prescriptions are Bupleurum-based formulas (including Xiao Chai Hu Tang, Da Chai Hu Tang, and Chai Hu Shu Gan San), Er Chen Tang, and Wen Dan Tang, with additional qi-tonifying and blood-activating herbs added or subtracted according to the specific symptoms, achieving certain therapeutic effects.

[0005] However, the above treatment plan still has unresolved core technical flaws: Firstly, existing treatment options lack a systematic and holistic understanding of the core common pathogenesis of coronary heart disease depression. They often focus on the single pathogenesis of "liver qi stagnation," and treatment tends to emphasize soothing the liver and relieving depression, promoting blood circulation and resolving phlegm. This easily overlooks the core characteristics of the disease, which is characterized by deficiency in the root and excess in the branch. There are problems of one-sided diagnosis and targeting, and neglecting one aspect while focusing on another. It is impossible to provide holistic intervention for the core pathogenesis of the disease. Secondly, existing treatment options fail to take into account the bidirectional pathological link between coronary heart disease and depression, making it impossible to simultaneously regulate physical illness and mental state, thus failing to break the vicious cycle of mutual causation between the two and resulting in limited long-term efficacy. Third, most existing sedative formulas use heavy sedative Chinese herbs, which can only improve superficial symptoms such as insomnia and irritability. They cannot address the core pathogenesis of the disease and thus cannot achieve both symptomatic relief and root cause treatment. Long-term use poses certain medication safety risks and limitations in efficacy.

[0006] Therefore, this invention is proposed. Summary of the Invention

[0007] To address the core shortcomings of existing treatments for coronary heart disease complicated with depression, such as drug interactions, significant side effects, and poor patient compliance caused by Western medicine's separate treatment approach, and the limitations of traditional Chinese medicine (TCM) in its understanding of the core pathogenesis of the disease, its limited treatment methods, and its inability to simultaneously regulate both physical and emotional states, this invention aims to provide a TCM composition for treating coronary heart disease complicated with depression and its preparation method. This aims to overcome the limitations of existing treatments in terms of pathogenesis and treatment methods. Based on the inventor's first proposed core pathogenesis of "Yang stagnation, phlegm and blood stasis, and malnourishment of the heart and spirit," a holistic intervention plan is established to achieve the therapeutic effects of promoting Yang and relieving stagnation, and simultaneously regulating both the heart and mind. This approach simultaneously improves myocardial ischemia and depressive disorders, avoids the risks of multi-drug combination therapy, and enhances treatment safety, compliance, and long-term clinical efficacy, providing a new TCM treatment option that addresses both the symptoms and root cause of coronary heart disease complicated with depression.

[0008] To achieve the above objectives, the present invention provides a traditional Chinese medicine composition for treating depression caused by coronary heart disease, wherein the depression caused by coronary heart disease includes depression complicated with coronary heart disease or depression after coronary heart disease, and comprises the following components by weight: 10-15 parts of Salvia miltiorrhiza; 8-12 parts of Panax ginseng; 8-12 parts of Ligusticum chuanxiong; 8-12 parts of Trichosanthes kirilowii; 8-12 parts of Paeonia lactiflora; 6-10 parts of Cyperus rotundus; 6-10 parts of Curcuma longa; 8-12 parts of Acanthopanax senticosus; 6-10 parts of Morinda officinalis; and 4-8 parts of Cinnamomum cassia.

[0009] It should be understood that the term "coronary heart disease depression" as used in this invention is a simplified expression, and its essence includes, but is not limited to, symptoms such as coronary heart disease complicated with depression, mild to moderate depression after coronary heart disease, and ischemic heart disease accompanied by depressive-like symptoms.

[0010] Further, the composition comprises, by weight: Salvia miltiorrhiza 12 parts, ginseng 10 parts, Ligusticum chuanxiong 10 parts, Trichosanthes kirilowii 10 parts, Paeonia lactiflora 10 parts, Cyperus rotundus 8 parts, Curcuma longa 8 parts, Acanthopanax senticosus 10 parts, Morinda officinalis 8 parts, Cinnamomum cassia 6 parts.

[0011] Further, the composition comprises, by weight: Salvia miltiorrhiza 10 parts, ginseng 12 parts, Ligusticum chuanxiong 8 parts, Trichosanthes kirilowii 12 parts, Paeonia lactiflora 8 parts, Cyperus rotundus 10 parts, Curcuma longa 6 parts, Acanthopanax senticosus 12 parts, Morinda officinalis 6 parts, Cinnamomum cassia 8 parts.

[0012] Further, the composition comprises, by weight: Salvia miltiorrhiza 15 parts, ginseng 8 parts, Ligusticum chuanxiong 12 parts, Trichosanthes kirilowii 8 parts, Paeonia lactiflora 12 parts, Cyperus rotundus 6 parts, Curcuma longa 10 parts, Acanthopanax senticosus 8 parts, Morinda officinalis 10 parts, Cinnamomum cassia 4 parts.

[0013] Further, the composition comprises, by weight: Ginseng 10 parts, Salvia miltiorrhiza 10 parts, Ligusticum chuanxiong 10 parts, Trichosanthes kirilowii 10 parts, Paeonia lactiflora 10 parts, Cyperus rotundus 8 parts, Curcuma longa 8 parts, Acanthopanax senticosus 10 parts, Morinda officinalis 8 parts, Cinnamomum cassia 6 parts.

[0014] The present invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a treatment for coronary heart disease complicated with depression or post-coronary heart disease depression.

[0015] Furthermore, the aforementioned coronary heart disease depression includes at least one of the following symptoms: Coronary heart disease complicated with mild to moderate depression; Depression following percutaneous coronary intervention (PCI) for coronary artery disease; Depression following coronary artery bypass grafting; Depression following medication treatment for coronary heart disease; Depression complicated by heart failure, including heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF). Ischemic heart disease accompanied by depressive-like symptoms.

[0016] Furthermore, the treatment of coronary heart disease with depression includes dual indicators for improving cardiac function and depressive-like behavior.

[0017] Furthermore, indicators for improving cardiac function include: increasing left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and the E' / A' ratio, and reducing myocardial damage and myocardial fibrosis; indicators for improving depressive-like behavior include improving cognitive impairment and reducing neuronal damage in the CA1 region of the hippocampus.

[0018] Furthermore, the drug exerts its therapeutic effect by regulating HIF-1α / BNIP3-mediated mitochondrial autophagy in cardiomyocytes and neurons.

[0019] The present invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, characterized in that it includes: The preparation method of the decoction includes the following steps: (1) Weigh each Chinese medicinal material according to the above-mentioned proportions, and clean and crush them appropriately; (2) First decoction: Add 3 times the weight of drinking water (about 500 mL) to the herbs, soak for 30 minutes, then heat to boiling, turn to low heat and keep simmering for 30 minutes, filter and collect the filtrate; (3) Second decoction: Add 3 times the weight of drinking water (about 500 mL) to the dregs again, heat to boiling in the same way, then turn to simmer for 30 minutes, filter and collect the filtrate; (4) Combine the filtrates obtained in steps (2) and (3), and concentrate them by heating over a low flame to finally prepare a decoction with a total volume of 100 mL, which is the decoction of the Chinese herbal composition of the present invention.

[0020] The method for preparing granules includes the following steps: (1) Extraction of Dan Gui Shu Xin Jie Yu Fang extract: The Chinese herbal composition according to claim 1 is soaked in 8-10 times the amount of water for 30 minutes, boiled over high heat, then simmered over low heat for 1 hour, filtered, and the residue is boiled in 4-6 times the amount of water for 1 hour, filtered, the two decoctions are combined, and heated and concentrated into a thick extract. (2) Granule preparation: Granulation was performed using dry extract. Specific method: The above-mentioned thick extract was mixed with an appropriate amount of dried sugar powder and dextrin to form a block, and then dried at room temperature or low temperature to obtain dry extract. Then it was pulverized into fine powder, and an appropriate amount of sugar powder and dextrin were added and mixed thoroughly. An appropriate concentration of ethanol was added as a wetting agent, and after mixing, it was granulated, dried and sized to obtain Dan Gui Shu Xin Jie Yu Fang granules.

[0021] Compared with the prior art, the beneficial effects of the present invention include: 1. Innovations in understanding the pathogenesis of depression in coronary heart disease Based on the understanding of the pathogenesis of coronary heart disease (CHD) depression in Traditional Chinese Medicine (TCM), this invention proposes that the main pathogenesis of CHD depression lies in "Yang stagnation (deficiency), phlegm and blood stasis, and malnourishment of the heart, body, and spirit," which is particularly closely related to abnormalities in the Yang (Qi) of the heart, liver, and kidneys. This viewpoint encompasses the key development of the current pathogenesis of CHD depression, further expanding TCM's understanding of its pathogenesis and overcoming the shortcomings of previous TCM approaches that failed to comprehensively understand the pathogenesis of CHD depression from the perspective of "Yang stagnation (deficiency)." Furthermore, in terms of syndrome differentiation and treatment, many approaches have been limited to the pathogenesis evolution based on "liver Qi stagnation," emphasizing the simultaneous treatment of the heart and liver while neglecting the important role of regulating kidney Yang (Qi) deficiency in the pathogenesis of CHD depression. Based on this new understanding, a comprehensive treatment method based on "promoting Yang and relieving stagnation, and regulating both hearts" is proposed. An innovative traditional Chinese medicine compound formula called "Dan Gui Shu Xin Jie Yu Fang" was created, consisting of ten Chinese herbs: Danshen, Ginseng, Chuanxiong, Gualou, Chishao, Xiangfu, Yujin, Ciwujia, Bajitian, and Guizhi.

[0022] 2. Innovations in the formulation and therapeutic effects of Dan Gui Shu Xin Jie Yu Fang (a traditional Chinese medicine formula for relieving depression and soothing the mind). This formula has the effects of invigorating qi and blood circulation, relieving chest congestion and promoting qi flow, and relieving stagnation and promoting yang. In the formula: Ginseng and Salvia miltiorrhiza are the principal herbs, possessing the effects of invigorating qi and blood circulation, relieving chest congestion and promoting qi flow, and relieving stagnation and promoting yang. Ligusticum chuanxiong is pungent and warm, capable of both invigorating blood and removing blood stasis, and also promoting qi circulation within the blood, acting as a qi-regulating herb in the blood; Paeonia lactiflora is bitter and cold in nature, clearing heat, cooling blood, dispersing blood stasis, and relieving pain. The combination of these two herbs not only enhances the effect of invigorating blood and removing blood stasis, but also leverages the power of qi to promote blood circulation, thus doubling the effect of promoting blood circulation and breaking up stagnation. Trichosanthes kirilowii and Cinnamomum cassia are also included. Trichosanthes kirilowii is sweet and cold in nature, entering the lungs, clearing phlegm and dispersing nodules, relieving chest congestion and promoting qi flow; Cinnamomum cassia is used to promote yang, dispel cold, and calm rebellious qi. Cinnamomum cassia is used to promote the yang of the heart and chest above, and to warm and transform the qi of the middle and lower jiao below, thus both promoting yang and calming rebellious qi. Calming rebellious qi prevents cold qi from rising upwards and invading the head, while promoting yang prevents cold qi from accumulating internally and obstructing the heart vessels. Turmeric and Cyperus are a classic herbal pair for soothing the liver and promoting blood circulation. They are mainly used to treat liver qi stagnation, having the effects of soothing the liver, promoting qi circulation, relieving depression, and regulating liver yang qi to assist the principal herb; at the same time, they clear heat from liver stagnation. Acanthopanax senticosus and Morinda officinalis have the effects of warming and tonifying kidney yang, strengthening the spleen and replenishing qi, and calming the mind and spirit. They are adjuvant herbs that warm and assist the yang of the whole body to ensure the source of yang qi. This formula does not use the traditional Chinese medicines with the effects of calming yang and stabilizing the mind, such as cinnabar, amber, dragon bone, and oyster shell, which are often used in the traditional treatment of coronary heart disease and depression. On the contrary, it focuses on the whole body and achieves the goal of "harmonizing both the heart and the mind" by "unblocking yang qi and eliminating stagnation and numbness". This forms a unique treatment strategy.

[0023] Technical effect: The above study mainly simulates the pathophysiological characteristics of clinical coronary heart disease complicated with depression. Based on the "two-hit" pathogenesis theory, our research group previously established research ideas and methods for establishing animal models, and established myocardial ischemia depression models in mice and rats to observe the intervention effect of Danggui Shujieyu Formula. Animal experiments have confirmed that Danggui Shujieyu Formula can simultaneously improve two core aspects of the pathological process of coronary heart disease depression: in the analysis of coronary heart disease with myocardial ischemia, this formula can improve cardiac function and ventricular remodeling after myocardial ischemia, and reduce myocardial tissue damage; at the level of animal behavioral evaluation, this formula can significantly regulate the depressive behavioral changes of animals with myocardial ischemia depression, and improve the pleasure, memory function and emotional state of animals to a certain extent. This is reflected in the improvement of multiple parameters such as sucrose preference in the sucrose preference test, latent escape time in the water maze test, platform crossing times in the spatial exploration test, immobility time in the tail suspension test, and total distance in the open field test. It should be pointed out that in this study on cardiac function decline or heart failure caused by coronary heart disease myocardial ischemia, mouse myocardial ischemia depression models and rat myocardial ischemia depression models were used to simulate two types of heart failure caused by myocardial ischemia in clinical coronary heart disease depression: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), which is more closely combined with clinical practice and provides an important reference for the reliability of clinical research. The results also show that Danggui Shujieyu Formula has a significant effect on improving cardiac function in the treatment of coronary heart disease depression, regardless of HFpEF or HFrEF, which further illustrates the practical value of Danggui Shujieyu Formula in the treatment of coronary heart disease depression.

[0024] 3. Innovative understanding of the correlation between autophagy of cardiac and brain tissue cells in coronary heart disease depression and the function of yang qi in traditional Chinese medicine In this part of the study, the method of rat left anterior descending coronary artery ligation combined with chronic unpredictable stimulation was used to systematically explore the intervention effect and mechanism of Dangui Shuxin Jieyu Formula on the coronary heart disease depression model. The results showed that Dangui Shuxin Jieyu Formula could significantly improve cardiac dysfunction in rats induced by left anterior descending coronary artery ligation combined with chronic unpredictable mild stress, reduce myocardial and neuronal damage, and ameliorate depression-related manifestations such as anhedonia and behavioral despair. Mechanistic studies found that increased autophagy occurred in the myocardium and brain tissue of rats in the model group, which may be the main mechanism leading to post-myocardial ischemia depression. It is currently believed that the deficiency of kidney yin and yang and essence-qi will reduce the function of various zang-fu organs, leading to the occurrence of pathological states such as qi deficiency, qi stagnation, blood deficiency, and cold pathogen, which in turn cause blockage of vessels and affect the functions of the heart governing the mind and the brain governing the spirit. Therefore, it is believed that yang qi deficiency and stagnation based on the theory of "yang governs activity", which fails to flow smoothly throughout the whole body, is the basic pathogenesis of coronary heart disease with depression. Through the intervention of Dangui Shuxin Jieyu Formula, which has the effects of "replenishing qi, activating blood, unblocking yang, relieving stagnation, nourishing the heart and tranquilizing the mind", warming and unblocking yang qi of the heart, liver and kidney can achieve the goal of "when yang (qi) reaches, stagnation resolves by itself; when blood vessels are unobstructed, obstruction eliminates itself, and both the heart and mental state are regulated", providing a treatment option that unblocks yang to invigorate the spirit and addresses both the symptoms and root causes for coronary heart disease with depression.

[0025] As mitochondria are the main site of cellular energy activities, mitochondrial homeostasis is the basis for ensuring the normal operation of energy metabolism. Under physiological conditions, mitochondrial homeostasis is mainly maintained through its own biogenesis, fission and fusion, and autophagy, so as to ensure coordinated structure and function and meet the body's energy supply demand. Therefore, mitochondrial function reflects, to a certain extent, the ascending and active physiological activities of "yang qi" in traditional Chinese medicine. From the perspective of traditional Chinese medicine, the promoting and qi-transforming effects of yang qi are extremely consistent in connotation with the effects of mitochondrial autophagy participating in body metabolism and information transmission. Yang qi deficiency leads to abnormal qi transformation, unfavorable dredging, impaired zang-fu function and decreased function, abnormal metabolism of essence, blood, body fluid, and gives rise to yin pathogens; similarly, altered mitochondrial autophagy function results in the abnormal metabolism of damaged organelles, harmful proteins and metabolites, leading to dysfunction of damaged cells and corresponding pathological changes of corresponding diseases.

[0026] Mitochondrial autophagy is also a major form of cellular autophagy. Therefore, improving cellular autophagy under pathological conditions and maintaining mitochondrial function also reflects the biological basis of the TCM treatment method of warming and invigorating Yang Qi. Current clinical research suggests that warming and invigorating kidney Yang has a good therapeutic effect on myocardial ischemia in coronary heart disease and is also one of the main treatments for depression. This study further found that myocardial ischemia-induced depression model rats showed increased cellular autophagy in myocardial and brain tissues, suggesting that insufficient cardiac function after myocardial ischemia leads to insufficient cerebral perfusion, resulting in autophagy in cardiac and brain tissues, thus causing cardiac and brain dysfunction. This, to some extent, reflects the dysfunction of important organs caused by insufficient Yang Qi and impaired circulation due to obstructed blood vessels. This study shows that Dan Gui Shu Xin Jie Yu Fang, which has the effect of warming and invigorating the Yang Qi of the heart (chest), liver, and kidneys, can exert a therapeutic and ameliorative effect on depression in coronary heart disease by improving HIF1α / BNIP3-mediated myocardial and neuronal cell autophagy. This suggests that the formula's effects of promoting blood circulation, resolving phlegm, and warming and invigorating Yang Qi are mainly manifested in improving autophagy of heart and brain tissue cells caused by insufficient blood perfusion, maintaining cardiac ejection and brain cognitive function, and ultimately reflecting the improvement or restoration of the function of "Yang Qi" in traditional Chinese medicine, leading to the recovery of organ function.

[0027] 4. Innovative study on the effects of Acanthopanax senticosus in the Dan Gui Shu Xin Jie Yu formula on the activity of cardiac and brain cells under hypoxic conditions. The properties and channels of the traditional Chinese medicine Acanthopanax senticosus are: sweet, slightly bitter, and warm. It enters the spleen, lung, kidney, and heart channels, and has the effects of invigorating qi and strengthening the spleen, tonifying the kidneys, and calming the mind. In this formula, it can warm and tonify the qi of the spleen and kidneys (i.e., both prenatal and postnatal qi) to promote the flow of yang qi throughout the body, and simultaneously has a calming effect due to tonifying yang. This study found that the main active ingredient of Acanthopanax senticosus, eleutheroside, has a good effect on improving the activity of cardiac and brain cells under hypoxic conditions, protecting against damage to cardiac and brain cells under hypoxic conditions. This suggests that in the pathological process of depression following myocardial ischemia in coronary heart disease, Acanthopanax senticosus plays an important protective role against insufficient cardiac function after myocardial ischemia, leading to insufficient cerebral perfusion and damage to cardiac and brain tissue cells. This also provides a reference for the use of warming yang and invigorating qi in the treatment of depression in coronary heart disease. Attached Figure Description

[0028] Figure 1 Data results on the effect of Dan Gui Shu Xin Jie Yu Fang on the sucrose preference of mice with myocardial ischemia and depression in different groups; Figure 2 A comparative study on the effect of Dan Gui Shu Xin Jie Yu formula on the sucrose preference of mice with myocardial ischemia and depression in different groups. Figure 3 Data on the effect of Dan Gui Shu Xin Jie Yu Fang on tail suspension immobility behavior in mice with myocardial ischemia and depression in different groups; Figure 4 Comparative graph of the effects of Dan Gui Shu Xin Jie Yu Fang on tail suspension immobility behavior in mice with myocardial ischemia and depression in different groups; Figure 5 Data on the effect of Dan Gui Shu Xin Jie Yu Fang on escape latency in the water maze test of mice with myocardial ischemia and depression in different groups; Figure 6 Comparative graph of the effects of Dan Gui Shu Xin Jie Yu Fang on escape latency in water maze test of mice with myocardial ischemia and depression in different groups; Figure 7 Data on the effect of Dan Gui Shu Xin Jie Yu Fang on the number of times mice with myocardial ischemia and depression traversed the water maze platform in each group; Figure 8 Comparative graph showing the effect of Dan Gui Shu Xin Jie Yu formula on the number of times mice with myocardial ischemia and depression can traverse the water maze platform in different groups; Figure 9 Data results on the effects of Dan Gui Shu Xin Jie Yu Fang on cardiac function in mice with myocardial ischemia and depression in different groups; Figure 10 M-mode echocardiography of the heart in mice with myocardial ischemia and depression in each group; Figure 11 Bar chart showing the effect of Dan Gui Shu Xin Jie Yu formula on cardiac systolic function in mice with myocardial ischemia and depression; Figure 12 Comparative chart of the effects of Dan Gui Shu Xin Jie Yu formula on cardiac systolic function in mice with myocardial ischemia and depression Figure 13 HE staining image (100x) showing the effect of Dan Gui Shu Xin Jie Yu Fang on myocardial tissue pathology in mice with myocardial ischemia and depression. Figure 14 Masson staining image showing the degree of myocardial fibrosis in mice with myocardial ischemia and depression, as indicated by the Dan Gui Shu Xin Jie Yu formula; Figure 15 Comparative graph showing the effects of Dan Gui Shu Xin Jie Yu Fang on the degree of myocardial fibrosis in mice with myocardial ischemia and depression; Figure 16 Figure showing the effect of Dan Gui Shu Xin Jie Yu Fang (a traditional Chinese medicine formula) on pathological damage in the CA1 region of the hippocampus in mice with myocardial ischemia and depression. Figure 17 Figure showing the effect of Gui Shuxin Jieyu Formula on changes in Nissl bodies in the hippocampus of mice with myocardial ischemia and depression. Figure 18 Figure showing the effect of Dan Gui Shu Xin Jie Yu formula on body weight in rats with myocardial ischemia and depression. Figure 19 Data on the effect of Dan Gui Shu Xin Jie Yu Fang on sucrose preference in rats with myocardial ischemia and depression; Figure 20 Comparative chart of the effects of Dan Gui Shu Xin Jie Yu formula on sucrose preference in rats with myocardial ischemia and depression Figure 21Data on the effect of Dan Gui Shu Xin Jie Yu Fang on tail suspension immobility behavior in rats with myocardial ischemia and depression; Figure 22 Comparative graph showing the effects of Dan Gui Shu Xin Jie Yu Fang on tail suspension immobility behavior in rats with myocardial ischemia and depression; Figure 23 Data on the effects of Dan Gui Shu Xin Jie Yu Fang on total distance, central region distance, and central latency in open field experiments of rats with myocardial ischemia and depression; Figure 24 Comparative graph showing the effects of Dan Gui Shu Xin Jie Yu Fang on total distance, central region distance, and central latency in open field experiments of rats with myocardial ischemia and depression; Figure 25 Data on the effects of Dan Gui Shu Xin Jie Yu Fang on the number of crossovers in the target quadrant and the number of platform crossings in the water maze test of rats with myocardial ischemia and depression; Figure 26 Comparative graph showing the effects of Dan Gui Shu Xin Jie Yu Fang on the number of crossovers in the target quadrant and the number of platform crossings in the water maze test of rats with myocardial ischemia and depression; Figure 27 Data on the effect of Dan Gui Shu Xin Jie Yu Fang (a traditional Chinese medicine formula) on the escape latency in the water maze test of rats with myocardial ischemia and depression; Figure 28 Comparative graph showing the effect of Dan Gui Shu Xin Jie Yu Fang (a traditional Chinese medicine formula) on the escape latency in the water maze test of rats with myocardial ischemia and depression. Figure 29 Data on the effects of Dan Gui Shu Xin Jie Yu Fang on cardiac function in rats with myocardial ischemia and depression; Figure 30 M-mode echocardiography of the heart in rats with myocardial ischemia and depression in each group; Figure 31 Comparative graph showing the effects of Dan Gui Shu Xin Jie Yu formula on cardiac function in rats with myocardial ischemia and depression; Figure 32 The effect of Dan Gui Shu Xin Jie Yu Fang on HE staining (100x) and Masson staining (200x) of rat myocardial tissue; Figure 33 Comparative graph showing the effects of Dan Gui Shu Xin Jie Yu Fang on the degree of myocardial fibrosis in rats with myocardial ischemia and depression; Figure 34 The effect of Dan Gui Shu Xin Jie Yu Fang on HE staining (100x) and Nissl staining (200x) of the CA1 region of the hippocampus in rat brain tissue; Figure 35 Data on the effect of Dan Gui Shu Xin Jie Yu formula on the expression of mitochondrial autophagy-related proteins in rat myocardial tissue; Figure 36 Comparative figure of the effects of Dan Gui Shu Xin Jie Yu formula on the expression of HIF-1α and autophagy-related proteins in the myocardial tissue of rats with coronary heart disease and depression. Figure 37 Data on the effect of Dan Gui Shu Xin Jie Yu formula on the expression of mitochondrial autophagy-related proteins in rat brain tissue; Figure 38 Comparative figure showing the effects of Dan Gui Shu Xin Jie Yu Fang on HIF-1α expression and autophagy-related protein expression in brain tissue of rats with coronary heart disease and depression; Figure 39 Figure showing the effect of different concentrations of Na2S2O4 on the morphology, viability, and confluence of H9c2 cells; Figure 40 Figure 1 shows the effect of different concentrations of Na2S2O4 on the morphology, viability and confluence of SH-SY5Y cells. Figure 41 Figure showing the effect of eleutheroside pretreatment on Na2S2O4-induced hypoxia in H9c2 cells; Figure 42 The figure shows the effect of Acanthopanax senticosin pretreatment on Na2S2O4-induced hypoxia in SH-SY5Y cells. Detailed Implementation

[0029] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] Before describing the specific technical solution of this invention, the technical concept of this invention will first be introduced. Since the formulation design of this invention revolves around the pathogenic mechanism first proposed by the inventors, the process of discovering and proposing this pathogenic mechanism also constitutes a contribution to the inventiveness of this invention. Specifically: To improve the efficacy of Traditional Chinese Medicine (TCM) in treating coronary heart disease (CHD)-related depression by addressing the various pathogenesis mechanisms of different diseases, the inventors, after summarizing long-term clinical experience, believe that while "qi stagnation, qi deficiency, phlegm-heat, and blood stasis" play important roles in the pathogenesis of CHD-related depression, a lack of comprehensive understanding of the core common pathogenesis of CHD-related depression leads to a failure to focus on intervening in the main pathogenesis in treatment. For example, if the focus is placed on soothing the liver, relieving depression, and promoting blood circulation to address "stagnation," "phlegm-heat" and "qi deficiency" may be overlooked, potentially resulting in certain deviations in TCM diagnosis and treatment. Therefore, treatment should focus on the characteristics of CHD-related depression as a comorbid disease, taking a holistic approach, emphasizing the common pivot of different pathogenesis mechanisms, and using syndrome differentiation and treatment to alleviate symptoms and improve quality of life.

[0031] Through the above analysis, the inventor expanded upon the theory of "Yang transforming into Qi, Yin forming form" described in the *Suwen* (Plain Questions) chapter "On the Correspondence of Yin and Yang," proposing that the key pathogenesis of depression in coronary heart disease lies in "Yang stagnation and deficiency, phlegm and blood stasis intertwining, and malnourishment of the heart, body, and spirit," which is particularly closely related to abnormalities in the Yang (Qi) of the heart, liver, and kidneys. Specifically, this is reflected in: 1. The heart governs the mind and its associated emotion is joy. The functions of the mind are based on the changes in Qi, especially Yang Qi. The mind and Yang Qi move together, manifesting externally during the day and returning internally at night, maintaining consistency with the movement and changes of Yang Qi. Therefore, the mind is the most direct and concentrated manifestation of the abundance of Yang Qi. The mind resides in Qi, and Qi transforms into the mind; abundant Qi leads to a vigorous mind, while deficient Qi leads to a diseased mind. Therefore, insufficient heart Yang leads to a loss of mental drive, resulting in a series of symptoms of "loss of mind," such as lethargy and mental confusion.

[0032] 2. The kidneys are the foundation of innate essence, and kidney yang determines whether the body's yang energy can perform its normal "governing spirit" function. Sufficient kidney yang ensures that the body's yang energy is vigorous. If kidney yang is insufficient, it cannot invigorate the spirit, resulting in symptoms such as lethargy and emotional apathy.

[0033] 3. The liver is a yang organ, yin in substance but yang in function. Its qi is ascending and active, governing the rise of yang qi throughout the body. Furthermore, the liver governs the free flow of qi, regulating its movement; the movement of qi throughout the body is closely related to the liver. Therefore, when liver yang is abundant and liver qi flows smoothly, one feels cheerful; when liver yang is deficient, its free flow is weak, qi is disordered, and stagnation occurs. Simultaneously, when liver yang fails to ascend properly, it cannot nourish the spirit and store the soul, which can also manifest as low mood. 4. Regarding emotions, the *Ling Shu* (Spiritual Pivot) states, "Those with abundant Yang are often joyful, while those with abundant Yin are often angry," indicating that the abundance of Yang Qi is a key influencing factor for emotions such as joy, anger, sorrow, and worry. When Yang Qi functions normally, the spirit is vigorous, the mind is clear and intelligent, energy is abundant, and people are generally joyful, thus ensuring normal mental activity. If Yang Qi function is abnormal, internal mental and emotional disorders and external physical motor dysfunction will occur. For example, Zhang Jiebin believed that "the heart stores the spirit, which is the essence of fire. When Yang is abundant, the spirit reigns, hence there is much joy and laughter; when Yang is deficient, Yin takes over, hence there is much worry and sorrow. Those with insufficient true Yang will inevitably experience fatigue and weakness." If Yang Qi is deficient, on the one hand, it can lead to Yang failing to nourish the spirit, resulting in symptoms such as low mood and lethargy; on the other hand, it can lead to Yang failing to nourish the tendons, resulting in physical symptoms such as pain and weakness in the limbs.

[0034] 5. In coronary heart disease, the kidneys are the source of innate essence, the abode of true Yin and Yang, and the organ where spirit resides and vital energy is connected. In particular, when kidney Yang is weak and the fire of the gate of life (Mingmen) declines, chest Yang becomes ineffective, leading to the internal generation of Yin evils such as phlegm accumulation and blood stasis. Simultaneously, the liver governs the free flow of Qi. After coronary heart disease, prolonged emotional distress and mental stimulation can disrupt the liver's function, causing stagnation of liver Qi. The liver Yang cannot generate and flow smoothly, resulting in poor circulation of Qi and blood, which can also lead to blood stasis and internal obstruction of phlegm. The internal generation of phlegm and blood stasis mutually binds and obstructs chest Yang, hindering the heart vessels, leading to insufficient chest Yang. Without the warmth of Yang Qi, the heart loses its pulse, and the obstruction of Qi and blood results in coronary heart disease (chest pain).

[0035] In summary, the inventors discovered that coronary heart disease falls under the category of "chest pain" or "chest obstruction" in Traditional Chinese Medicine (TCM), and depression is similar to "depression" in TCM. The two are closely related, influencing each other and acting as a cause and effect. The pathogenesis of depression in coronary heart disease lies in "stagnation of Yang Qi, inability to promote the flow of Qi and blood, phlegm and blood stasis, and malnourishment of the heart, body, and spirit." It is a syndrome of deficiency in the root and excess in the branch. The root deficiency is attributed to the Yang deficiency and weakness of the heart, liver, and kidneys, leading to poor circulation of Qi and blood; the branch excess is due to internal obstruction by phlegm and blood stasis. When Yang Qi is stagnant, Qi and blood circulation becomes obstructed, leading to internal pathogens. This further hinders the flow of Qi and blood, damaging Yang Qi. On one hand, this results in insufficient Yang Qi in the chest, obstructed Yang Qi flow, blood stasis in the heart vessels, and malnourishment of the mind, leading to coronary heart disease (chest pain) and depression. On the other hand, the inability of Yang Qi to reach the top of the head prevents the clear Yang from ascending to the sensory orifices, causing mental confusion (depression). Therefore, this invention addresses the clinical challenge of coronary heart disease and depression. Based on the pathogenesis of "stagnation and inability to expanse Yang Qi" in both coronary heart disease and depression, this invention constructs a holistic TCM intervention strategy that can invigorate Qi and blood, promote Yang Qi circulation, relieve stagnation, nourish the heart, and calm the mind. Based on this, the proposed TCM composition, "Dan Gui Shu Xin Jie Yu Fang," has the effects of invigorating Qi and blood, relieving chest congestion, promoting Yang Qi circulation, and relieving stagnation. This formula aims to achieve the goal of "relieving stagnation by invigorating the Yang of the heart, liver, and kidneys, and eliminating phlegm and blood stasis" through the combination of herbal pairs. The aim is to provide a treatment option for coronary heart disease depression that addresses both the root cause and symptoms by promoting Yang and invigorating the spirit. The proposed patent application for this compound formula primarily addresses the shortcomings of existing TCM formulas for treating coronary heart disease depression that focus on soothing the liver, promoting blood circulation, regulating Qi, and resolving phlegm. It specifically addresses the deficiencies in TCM formulas that address the core pathogenesis of coronary heart disease depression—"Yang stagnation, phlegm and blood stasis, and malnourishment of the heart and spirit"—by providing a symptom-based treatment approach.

[0036] <Example> This invention provides a traditional Chinese medicine composition for treating depression caused by coronary heart disease, referred to as Dan Gui Shu Xin Jie Yu Fang in the following embodiments. The specific formulation and preparation method of this traditional Chinese medicine composition are described below.

[0037] Example 1 This invention provides a traditional Chinese medicine composition for treating depression in patients with coronary heart disease, comprising the following components by weight: 12 parts of Salvia miltiorrhiza, 10 parts of ginseng, 10 parts of Ligusticum chuanxiong, 10 parts of Trichosanthes kirilowii, 10 parts of Paeonia lactiflora, 8 parts of Cyperus rotundus, 8 parts of Curcuma longa, 10 parts of Acanthopanax senticosus, 8 parts of Morinda officinalis, and 6 parts of Cinnamomum cassia.

[0038] The dosage form is a decoction, and the preparation method includes: (1) Weigh each Chinese medicinal material according to the drug ratio in this prescription, and clean and crush them appropriately; (2) First decoction: Add 3 times the weight of drinking water (about 500 mL) to the herbs, soak for 30 minutes, then heat to boiling, turn to low heat and keep simmering for 30 minutes, filter and collect the filtrate; (3) Second decoction: Add 3 times the weight of drinking water (about 500 mL) to the dregs again, heat to boiling in the same way, then turn to simmer for 30 minutes, filter and collect the filtrate; (4) Combine the filtrates obtained in steps (2) and (3), and concentrate them by heating over a low flame to finally prepare a decoction with a total volume of 100 mL, which is the decoction of the Chinese herbal composition of the present invention.

[0039] Example 2 The raw materials and preparation method are the same as in Example 1, except for the different proportions. In this example, the composition comprises, by weight, the following components: Salvia miltiorrhiza 10 parts, ginseng 12 parts, Ligusticum chuanxiong 8 parts, Trichosanthes kirilowii 12 parts, Paeonia lactiflora 8 parts, Cyperus rotundus 10 parts, Curcuma longa 6 parts, Acanthopanax senticosus 12 parts, Morinda officinalis 6 parts, Cinnamomum cassia 8 parts.

[0040] Example 3 The raw materials and preparation method are the same as in Example 1, except for the different proportions. In this example, the composition comprises, by weight, the following components: Salvia miltiorrhiza 15 parts, ginseng 8 parts, Ligusticum chuanxiong 12 parts, Trichosanthes kirilowii 8 parts, Paeonia lactiflora 12 parts, Cyperus rotundus 6 parts, Curcuma longa 10 parts, Acanthopanax senticosus 8 parts, Morinda officinalis 10 parts, Cinnamomum cassia 4 parts.

[0041] Example 4 The raw materials and preparation method are the same as in Example 1, except for the different proportions. In this example, the composition comprises, by weight, the following components: Ginseng 10 parts, Salvia miltiorrhiza 10 parts, Ligusticum chuanxiong 10 parts, Trichosanthes kirilowii 10 parts, Paeonia lactiflora 10 parts, Cyperus rotundus 8 parts, Curcuma longa 8 parts, Acanthopanax senticosus 10 parts, Morinda officinalis 8 parts, Cinnamomum cassia 6 parts.

[0042] The Dan Gui Shu Xin Jie Yu formula in Examples 1-4 has the following beneficial effects: Efficacy: Invigorates Qi and blood circulation, relieves chest tightness and promotes Qi flow, promotes Yang and relieves depression. Indications: Mild to moderate depression in patients with coronary artery disease (including those who have undergone coronary artery disease medication, percutaneous coronary intervention (PCI), and surgical coronary artery bypass grafting).

[0043] Analysis of Prescription: Ginseng Radix et Rhizoma and Salviae Miltiorrhizae Radix et Rhizoma are used together as the monarch herbs, with the effects of supplementing qi, activating blood, freeing the chest, moving qi, activating yang and relieving depression. Chuanxiong Rhizoma, which is acrid in flavor and warm in property, can both promote blood circulation to remove blood stasis and resolve qi stagnation in blood, so it is known as qi drug in blood. Paeoniae Radix Rubra, which is bitter and cold in nature and flavor, can clear heat, cool blood, dissipate blood stasis and relieve pain. The compatibility of these two drugs can enhance the effect of promoting blood circulation and removing blood stasis, and with the power of qi moving to promote blood circulation, the effect of promoting blood circulation and resolving stagnation is greatly increased. For Trichosanthis Fructus and Cinnamomi Ramulus, Trichosanthis Fructus is sweet in flavor, cold in nature and acts on the lung, which can eliminate phlegm and resolve stagnation, regulate qi in the middle Jiao, open the chest and resolve phlegm, while Cinnamomi Ramulus can activate yang, dispel cold, and descend reversed qi to calm counterflow. Cinnamomi Ramulus can disperse and unblock the yang of the heart and chest upward, and warm and promote qi movement of the middle and lower Jiao downward; it can both activate yang and descend reversed qi. With its effect of descending reversed qi, yin-cold qi will not reverse upward to invade the vertex; with its effect of activating yang, yin-cold qi will not condense internally to block the heart vessels. Curcumae Radix and Cyperi Rhizoma are a classic herbal pair in traditional Chinese medicine for soothing the liver and activating blood, which are mainly used for liver depression and qi stagnation, with the effects of soothing the liver and regulating qi, activating blood and relieving depression, and regulating liver yang to assist the efficacy of the monarch herbs. Acanthopanacis Senticosi Radix et Rhizoma seu Caulis and Morindae Officinalis Radix, which have the effects of warming and tonifying kidney yang, invigorating spleen to replenish qi, and calming the heart to tranquilize mind, act as assistant herbs. They warm and tonify the yang of the whole body to consolidate the origin of yang qi.

[0044] The preparation method of the water decoction described in the present invention is highly compatible with the formula characteristics of Dangu Shuxin Jieyu Prescription and achieves synergistic effect: the prescription takes Ginseng Radix et Rhizoma and Salviae Miltiorrhizae Radix et Rhizoma as monarch herbs, and is compatible with herbs with effects of warming yang, replenishing qi, activating blood, unblocking yang, soothing the liver, relieving depression, resolving phlegm and dissipating stagnation. Most of the herbs contain heat-sensitive and water-soluble active ingredients such as saponins, phenolic acids, volatile oils and polysaccharides. The mild process of crushing medicinal materials, soaking with 3 times the amount of water, decocting twice under slightly boiling condition, and concentrating at low temperature with small fire can maximize the dissolution of core active substances such as ginsenosides, danshensu, ligustrazine, acanthopanax senticosus glycosides and cinnamon volatile oil, avoid the decomposition and destruction of active ingredients caused by high-temperature and long-time decoction, and fully retain the compatibility efficacy of the prescription of supplementing qi, activating blood, unblocking yang, relieving depression, freeing chest, moving qi, nourishing heart and tranquilizing mind. Meanwhile, through combining two decoctions and concentrating to 100 mL, the drug solution has uniform concentration and stable dosage, which ensures the synergistic effect of all herbs in the compatibility of monarch, minister, assistant and guide herbs, accurately exerts therapeutic effect targeting the core pathogenesis of coronary heart disease with depression: yang depression debilitation, intermin-gling of phlegm and blood stasis, and heart-spirit malnutrition, and further enhances the clinical advantage of the prescription in simultaneously regulating the heart and mental state, and treating both symptoms and root causes.

[0045] <Test Example> 1. Intervention effect of Dangu Shuxin Jieyu Prescription on mice with myocardial ischemia complicated with depression 1.1 Materials (1) Animals Male BALB / c mice, SPF grade, with body weight of 18±2 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with animal license No. SCXK (Beijing) 2021-0006. The animals were raised in the Laboratory Animal Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences, with license No. SYXK (Beijing) 2023-0053. This experiment was approved by the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences, with ethical approval No. 2024XLC061.

[0046] (2) Drugs and reagents The formula for Dan Gui Shu Xin Jie Yu Fang consists of Cyperus rotundus (batch number 2408031), Cinnamomum cassia, Trichosanthes kirilowii, Curcuma longa, Acanthopanax senticosus (batch number 2410011), Ginseng slices (batch number 2411021), Paeonia lactiflora (batch number 2409021), Morinda officinalis (batch number 2409011), Salvia miltiorrhiza (batch number 2410021), and Ligusticum chuanxiong (batch number 2412011), provided by Hebei Baicao Kangshen Pharmaceutical Co., Ltd. 10g each of ginseng, salvia miltiorrhiza, chuanxiong rhizome, trichosanthes fruit, red peony root, 8g of cyperus rhizome, 8g of turmeric, 10g of eleutherococcus senticosus, 8g of morinda root, and 6g of cinnamon twig (as in Example 4) were weighed and placed in a round-bottom flask. Ten times the volume of pure water was added, and the mixture was refluxed at 80°C for three extractions, each lasting 2 hours. The three extracts were combined and concentrated under reduced pressure using a rotary evaporator at 70°C and 0.08 MPa to obtain a brownish-red extract with a crude drug content of 1.5g / ml. Based on the conversion factor of body surface area between human and mouse clinical doses, the high-dose group was set at 12g / kg, the low-dose group at 6g / kg, and the positive control drug fluoxetine tablets were administered at a dose of 10 mg / kg. The positive control drug fluoxetine tablets were provided by Changzhou No. 4 Pharmaceutical Co., Ltd. (batch number: H19980139). Pentobarbital, supplied by Beijing Chemical Reagent Company (batch number 20402).

[0047] It should be noted that the traditional Chinese medicine compositions described in the claims of this invention and in clinical applications mainly adopt decoction or granules to retain the clinical efficacy characteristics of the decoction to the greatest extent.

[0048] In the pharmacodynamic test examples of the present invention, in order to obtain a high concentration of the effective fraction for animal gavage administration and cell experiment processing, and at the same time to ensure the stability of experimental data, a preparation process of reflux extraction combined with vacuum concentration (i.e. reflux extract) was adopted.

[0049] Although the extraction process parameters differ, the reflux extract used in the experimental examples and the decoction and granules described in the claims originate from the exact same traditional Chinese medicine formula (Dan Gui Shu Xin Jie Yu Fang). Both exhibit a high degree of consistency in the types of their main active ingredients. Therefore, the pharmacodynamic studies conducted using the reflux extract in the experimental examples fully support the technical efficacy of the traditional Chinese medicine composition of this invention in treating coronary heart disease and depression.

[0050] (3) Instruments Electronic temperature-controlled heating mantle, manufactured by Tianjin Test Instrument Co., Ltd.; R2002 rotary evaporator, manufactured by Shanghai Shenke Biotechnology Co., Ltd.; Vevo2100 high-resolution ultrasound imaging system, manufactured by VisualSonics, Canada; CRYOSTAR NX50 cryostat, manufactured by Thermo Scientific, USA; IECCL3R low-temperature refrigerated centrifuge, manufactured by Thermo Scientific, USA; ZS-001 Morris water maze video analysis system, manufactured by Beijing Zhongshidichuang Co., Ltd.; ALC-V8 small animal ventilator, manufactured by Shanghai Alcot Biotechnology Co., Ltd.; BX-53 upright optical microscope acquisition system, manufactured by Olympus, Japan.

[0051] 1.2 Methods (1) Establishment of a mouse model of myocardial ischemia combined with depression Nine stimuli were used, including 24-hour fasting; 24-hour water deprivation; 24-hour bedding soaking; bedding removal and cage tilting for 12 hours; cage shaking for 5 minutes; tail clamping for 5 minutes; day-night reversal; swimming in 4°C cold water for 5 minutes; swimming in 45°C hot water for 5 minutes; and restraint stress (using pretreated 50 mL centrifuge tubes as restraint devices) for 3 hours. One to two stimuli were randomly selected daily (avoiding repeated stimuli), and social failure was performed every 7 days (mice were replaced in the same cage) to establish a mouse model of chronic unpredictable stress (CUMS). A mouse model of myocardial ischemia was induced by intraperitoneal injection of isoproterenol (ISO). The intraperitoneal injection dose of isoproterenol was 100 mg / kg, administered for 2 consecutive days to induce myocardial ischemia and heart failure. Except for the blank control group, all mice were given CUMS stimulation for 2 weeks, followed by intraperitoneal injection of isoproterenol to establish the mouse model of myocardial ischemia, and then gavage administration was initiated. CUMS stimulation continued for 4 weeks. All mice underwent various indicator tests after 6 weeks.

[0052] (2) Grouping and administration All animals were randomly divided into 6 groups (12 animals per group) according to their body weight: control group, model group (myocardial ischemia combined with depression), positive drug group (fluoxetine, 10 mg / kg), low-dose group of Dan Gui Shu Xin Jie Yu Fang (SXXX-L) (9 g crude drug / kg), medium-dose group of Dan Gui Shu Xin Jie Yu Fang (SXXX-M) (18 g crude drug / kg), and high-dose group of Dan Gui Shu Xin Jie Yu Fang (SXXX-H) (36 g crude drug / kg).

[0053] 1.3 Detection Indicators (1) Consumption of sucrose water (sucrose water test) Mice were acclimatized to a 1% sucrose solution one week prior to the formal experiment. After acclimatization, all mice were deprived of food and water for 23 hours. Then, all mice were housed in individual cages and given free access to two pre-weighed bottles containing 1% sucrose solution (1% w / v) and pure water for one hour. The positions of the two bottles were changed after 30 minutes of the experiment. At the end of the experiment, the bottles containing 1% sucrose solution and pure water were reweighed and the weight recorded. The percentage difference in sucrose preference was calculated using the following formula: Sucrose preference (%) = (Sucrose consumption / (Sucrose consumption + Pure water consumption)) × 100.

[0054] After modeling, a sucrose preference experiment was conducted. Mice were housed individually and fasted from food and water for 23 hours prior to the test. Each cage was placed with one bottle of pure water and one bottle of sucrose solution (1% sugar content). The bottles were identical in appearance, and the mice were allowed to drink freely for 1 hour. After 30 minutes, the bottles were moved to disrupt the mice's established habits. The consumption of sucrose solution and pure water was recorded after the experiment. Sucrose preference (%) = sucrose intake / (sucrose intake + water intake) × 100.

[0055] (2) Tail suspension test Mice in each group were gently removed from their cages and secured to the edge of a table with medical tape, 1 cm from the tip of their tails, in a head-down position. The height of the mouse's tail tip from the ground was approximately 30 cm. The test lasted for 6 minutes, with immobility time measured and analyzed during the last 4 minutes.

[0056] (3) Water maze experiment A water maze system consisting of a swimming pool (150 cm in diameter and 50 cm in height) and a platform (10 cm in diameter and 20 cm in height) filled with 21 cm of water was used. The swimming pool was divided into four quadrants, and the platform was fixed in the fourth quadrant. The water maze experiment was conducted in two main phases: orientation navigation and spatial exploration. Orientation navigation experiment: This tested the mouse's ability to learn the platform's location. Training was conducted continuously for 5 days. Training was conducted 4 times in each time period, with the mouse placed in the water from each of the four quadrants. If the mouse climbed onto the platform within 90 seconds and remained there for more than 3 seconds, it was considered to have found the platform; this was the escape latency period. If the mouse failed to find the platform within 90 seconds, it was guided to the platform for 10 seconds to familiarize itself with it; this latency period was calculated as 90 seconds. Each training session was spaced 5 minutes apart. The average latency period in each of the four directions for each time period was calculated as the final swimming result for that day.

[0057] (4) Space exploration experiments This experiment is primarily used to test mice's ability to remember the spatial location of platforms after they have learned to locate them. On the morning of the 6th day of the water maze experiment, the platforms were removed, and rats were placed in the water at any random entry point. The number of times the mice crossed the quadrant where the platform was located and the number of times they crossed the original platform area within 90 seconds was observed and recorded.

[0058] (5) Cardiac systolic and diastolic function testing Mice in each group were anesthetized by intraperitoneal injection of 0.1% sodium pentobarbital solution at a dose of 10 mL / kg. The mice were fixed in a supine position, and the heart rhythm was stabilized before testing. A high-resolution small animal ultrasound imaging system was used, with the probe placed on the long axis section at the level of the papillary muscles, at a frequency of 17.5 MHz in M-mode. The main indicators of heart rate and cardiac systolic function were measured, including left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and stroke volume (SV); ventricular wall thickness indicators, including left ventricular anterior wall diastolic thickness (LVAWd) and left ventricular anterior wall systolic thickness (LVPWs). Subsequently, the diastolic function of the heart in each group of mice was measured. The main steps were as follows: an apical four-chamber view was obtained from the lower left side of the animal's thorax; an ultrasound probe was placed at the junction of the mitral valve and the interventricular septum; tissue Doppler ultrasound was used to measure the peak values ​​of E' and A', and the ratio E' / A' was calculated. All indicators must be measured continuously for 3 cardiac cycles.

[0059] (6) HE staining and Masson staining of cardiac tissue After sacrifice, the hearts of mice in each group were quickly removed, and the heart tissue was longitudinally sectioned, fixed in 4% paraformaldehyde for 24 hours, then dehydrated in a gradient of alcohols, cleared in xylene, and then embedded in paraffin. The tissue was then cut into 10 μm sections. One portion underwent dewaxing, hydration, hematoxylin staining, differentiation, eosin staining, and dehydration, followed by xylene staining for 2 minutes and mounting with neutral resin. Another portion underwent dewaxing, hydration, Weigert iron hematoxylin staining, differentiation, reverse blue staining, Ponceau S and fuchsin staining, phosphomolybdic acid staining, aniline blue staining, dehydration, and mounting. HE staining was used to observe the morphological characteristics of myocardial injury, and Masson staining was used to observe the degree of myocardial fibrosis.

[0060] (7) HE staining and Nissl body staining of brain tissue After sacrifice, the brains of mice in each group were quickly removed. Paraffin sections of the brain tissue were dewaxed and hydrated, then immersed in Nissl stain for 5 minutes, washed with water, differentiated with 0.1% glacial acetic acid, washed with water, dried in an oven, cleared with xylene for 10 minutes, and mounted. Pathological morphological changes in the CA1 region of the hippocampus of rats in each group were observed under a light microscope.

[0061] (8) Statistical processing All experimental data are expressed as mean ± standard deviation (x ± s). If the data in each group conform to a normal distribution and have homogeneity of variance, a one-way ANOVA is used. P < 0.05 is considered statistically significant.

[0062] 1.3 Results (1) Effects of Dan Gui Shu Xin Jie Yu Formula on the sucrose preference, tail suspension test, water maze test and spatial exploration behavior of mice with myocardial ischemia and depression The results of the saccharin preference experiment showed that, compared with the blank control group, the saccharin preference of mice in the model group was significantly reduced (P < 0.01). Compared with the model group, the saccharin preference of mice in the positive control group increased most significantly (P < 0.01); at the same time, the saccharin preference of mice in the low-dose, medium-dose, and high-dose groups of Dangui Shuxin Jieyu Fang were all significantly increased (P < 0.05). (See...) Figure 1 , 2 ).

[0063] The tail suspension test results showed that, compared with the blank control group, the resting time of mice in the model group was significantly increased (P < 0.01), while compared with the model group, the resting time of mice in the high-dose Dangui Shuxin Jieyu Formula and the positive control group was significantly shortened (P < 0.05 or P < 0.01). (See...) Figure 3 and Figure 4 ).

[0064] The water maze test results showed that during the 1-4 day positioning and navigation test, the escape latency of mice in all groups shortened with increasing training time. Compared with the blank control group, the escape latency of mice in the model group was significantly prolonged on days 2, 3, and 4 (P < 0.05); compared with the model group, the escape latency of mice in the high-dose Dan Gui Shu Xin Jie Yu Fang group was significantly shortened on days 3, 4, and 5 (P < 0.05). Meanwhile, the escape latency of the positive control group was significantly shortened on days 2, 3, and 4 (P < 0.05). (See...) Figure 5 and Figure 6 ).

[0065] The results of the space exploration experiment showed that, on day 6, compared with the blank control group, the number of platform crossings in the model group mice was significantly reduced (P < 0.01). Compared with the model group, the number of platform crossings in the high-dose Dangui Shuxin Jieyu Formula and positive drug groups was increased (P < 0.05). (See...) Figure 7 and Figure 8 ).

[0066] (2) Effects of Dan Gui Shu Xin Jie Yu Formula on cardiac function in mice with myocardial ischemia and depression Compared with the blank control group, the cardiac systolic function indices EF, FS, LVAWs, and LVAWd in the model group mice all showed a decreasing trend, but the difference was not statistically significant; at the same time, E' / A' was significantly decreased (P<0.01), indicating that the diastolic function of the heart in the model group mice was impaired to some extent. Compared with the model group mice, the E' / A' of the high-dose Dangui Shuxin Jieyu Fang group mice was significantly increased (P<0.01). See Figure 9-12 .

[0067] (3) Effects of Dan Gui Shu Xin Jie Yu Formula on myocardial tissue pathology in mice with myocardial ischemia and depression HE staining of myocardial tissue showed that in the normal group mice, the myocardial fibers were uniformly stained, neatly arranged, with intact cell structure and clear nuclei; while in the model group mice, myocardial fibers were broken, disordered, and accompanied by interstitial edema and neutrophil infiltration, indicating inflammation. After intervention with traditional Chinese medicine, myocardial damage was significantly improved, and the pathological changes in myocardial tissue were similar between the positive control group and the model group. (See...) Figure 13 .

[0068] Masson staining showed that collagen fibers in the myocardial interstitium of the normal group were sparsely and orderly distributed; in the model group, collagen fibers were significantly hyperplastic, disordered, and accompanied by necrotic myocardial tissue. After traditional Chinese medicine intervention, collagen fiber hyperplasia was somewhat reduced, but the number of collagen fibers in the positive control group was not significantly reduced compared to the model group. Figure 14 and 15 .

[0069] (4) Effects of Dan Gui Shu Xin Jie Yu Formula on pathological damage in the CA1 region of the hippocampus in mice with myocardial ischemia and depression In the control group, the pyramidal cells in the cerebral cortex and hippocampus of mice were neatly and densely arranged; the pyramidal cells were structurally intact, with clear outlines, large and round nuclei, uniform staining, and clear nucleoli. Compared with the control group, the number of cortical neurons was significantly reduced, and neurophilic cell phenomena were observed. The density of hippocampal pyramidal cells was significantly reduced, their arrangement was loose, the layers were reduced and disordered, deformed nerve cells appeared, mostly triangular, with absent cytoplasm, unclear nucleoli, pyknosis, and many deeply stained cells, alternating with normal nerve cells; microglia infiltration was also observed. These pathological changes were somewhat improved in mice in the medium-dose group of Dan Gui Shu Xin Jie Yu Fang. Significant improvement was observed in mice in the high-dose group of Dan Gui Shu Xin Jie Yu Fang. See Figure 16 .

[0070] In Nissl staining, neurons in the CA1 region of the hippocampus of mice in the normal group were densely packed, and Nissl bodies were clear and intact; in the model group, the number of damaged neurons in this region increased, their distribution was sparse and disordered, and Nissl bodies were significantly reduced or disintegrated. The arrangement of neurons in the hippocampus of mice in the Dan Gui Shu Xin Jie Yu formula group and the positive control group was improved compared to the model group, and the number of damaged neurons decreased. (See...) Figure 17 .

[0071] 2. Intervention Effect of Dangui Shujieyu Formula on Rats with Myocardial Ischemia Complicated with Depression 2.1 Materials (1) Animals Sixty SPF-grade male rats, SPF grade, weighing 180±20 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with animal license number: SCXK (Jing) 2021-0006. The animals were raised in the Laboratory Animal Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences, with license number: SYXK (Jing) 2023-0053. This experiment was approved by the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences, with ethical approval number: 2024XLC061.

[0072] (2) Drugs and Reagents Danggui Shujieyu Formula consists of Cyperi Rhizoma (batch number 2408031), Cinnamomi Ramulus, Trichosanthis Fructus, Curcumae Radix, Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis (batch number 2410011), Ginseng Tablets (batch number 2411021), Paeoniae Radix Rubra (batch number 2409021), Morindae Officinalis Radix (batch number 2409011), Salviae Miltiorrhizae Radix et Rhizoma (batch number 2410021), and Chuanxiong Rhizoma (batch number 2412011), which are provided by Hebei Baicao Kangshen Pharmaceutical Co., Ltd. Weigh out respectively 10 g of Ginseng, 10 g of Salviae Miltiorrhizae Radix et Rhizoma, 10 g of Chuanxiong Rhizoma, 10 g of Trichosanthis Fructus, 10 g of Paeoniae Radix Rubra, 8 g of Cyperi Rhizoma, 8 g of Curcumae Radix, 10 g of Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis, 8 g of Morindae Officinalis Radix, and 6 g of Cinnamomi Ramulus (that is, the ratio in Example 4), place them in a round-bottom flask, add 10 times the volume of pure water, conduct reflux extraction at 80°C for 3 times, 2 hours each time, combine the 3 extracts, and concentrate under reduced pressure at 70°C and 0.08 MPa using a rotary evaporator to obtain a brown extract, thus obtaining an extract with a crude drug content of 1.5 g / ml. According to the body surface area conversion coefficient of clinical doses between humans and rats, the high-dose group is set at 12 g / kg and the low-dose group at 6 g / kg. Flupentixol and Melitracen Tablets are provided by Chongqing Shenghuaxi Pharmaceutical Co., Ltd., batch number: H20153122. Pentobarbital is provided by Beijing Chemical Reagent Company, batch number: 20402.

[0073] (3) Instruments Electronic temperature-controlled heating mantle, manufactured by Tianjin Test Instrument Co., Ltd.; R2002 rotary evaporator, Shanghai Shenke Biotechnology Co., Ltd.; Vevo2100 high-resolution ultrasound imaging system, VisualSonics, Canada; Supermaze open field analysis system, Shanghai Xinruan Information Technology Co., Ltd.; CRYOSTAR NX50 cryostat, Thermo Scientific, USA; IECCL3R low-temperature refrigerated centrifuge, Thermo Scientific, USA; ZS-001 Morris water maze video analysis system, Beijing Zhongshidichuang Co., Ltd.; ALC-V8 small animal ventilator, Shanghai Alcot Biotechnology Co., Ltd.; BX-53 upright optical microscope acquisition system, Olympus, Japan.

[0074] 2.2 Methods (1) Establishment of a rat model of myocardial ischemia combined with depression A rat model of myocardial ischemia was established by ligation of the left anterior descending coronary artery after one week of acclimatization. The rats were anesthetized by intraperitoneal injection of 1% sodium pentobarbital (2 ml / kg). After anesthesia, the rats were intubated and connected to a small animal ventilator, with tidal volume (10 ml / kg) and respiratory rate adjusted (breathing ratio 1:1, respiratory rate 75 breaths / min). Blunt dissection was performed in the 2nd-3rd intercostal space on the left side of the sternum, the ribs were spread to expel the heart, and the left anterior descending coronary artery was ligated with a 6-0 ophthalmic suture needle 2-3 mm above the midpoint of the line connecting the lower edge of the left atrial appendage and the apex of the heart. Successful model establishment was indicated by whitening of the left anterior wall myocardium at the apex and sustained ST segment elevation with kyphosis in the limb leads on electrocardiogram. Postoperatively, the rats were kept warm on a 30°C constant-temperature electric blanket, and all procedures were performed in an SPF environment. The normal control group rats underwent only threading of the suture without ligation. On the second day after surgery, except for the normal control group, the other groups were given chronic unpredictable mild stress (CUMS) for 45 consecutive days. The stimulation methods included day-night reversal, 24 h of wet bedding, 5 min of tail suspension, 5 min of swimming in ice water, 5 min of tail clamping, 24 h of tilted cage, and social failure, with 1-2 methods randomly selected each day.

[0075] (2) Grouping and administration Sixty rats were randomly divided into four groups: a blank control group (Control), a coronary heart disease combined with depression model group (Model), a high-dose Dangui Shuxin Jieyu Fang (SSSX-H) group, a low-dose Dangui Shuxin Jieyu Fang (SSSX-L) group, and a positive control group (flupentixol / melitracen tablets, 0.45 mg / kg), with 12 rats per group. Based on the conversion factor of body surface area between human and rat clinical doses, the high-dose Dangui Shuxin Jieyu Fang group was determined to be 12 g / kg, and the low-dose group was determined to be 6 g / kg.

[0076] 2.3 Detection Indicators (1) Weight changes All animals were recorded as day 0 on the day the administration of the drug via gavage began, and their body weight was measured on days 15, 30, and 45. An electronic balance with an accuracy of 0.1 g was used for weighing. Each rat was placed individually in a clean weighing box for each measurement, and the values ​​were recorded after they stabilized.

[0077] (2) Sucrose water experiment Rats were acclimatized to a 1% sucrose solution one week before the formal experiment. After acclimatization, all rats were deprived of food and water for 24 hours. Then, each rat was housed in a separate cage and given free access to two pre-weighed bottles containing 240 ml of sucrose solution (1% w / v) and 240 ml of pure water for one hour. The bottles were switched after 30 minutes of the experiment. At the end of the experiment, the bottles containing the 1% sucrose solution and the pure water were weighed again and the weight recorded. The percentage difference in sucrose preference was calculated using the following formula: Sucrose preference (%) = (Sucrose consumption / (Sucrose consumption + Pure water consumption)) × 100 (3) Open field experiment Rats were exposed to rectangular containers (50×50×45cm) placed in a dimly lit room. A camera was positioned at the center of the ceiling above the container to record the rats' movements. Movement was monitored using a computerized video tracking system based on the S-MART program. During the 20-minute test, the distance traveled in the last 10 minutes was recorded. Movement activity was measured in centimeters. Between tests, the floor of each test chamber was thoroughly cleaned with 75% ethanol to prevent residual rat odor from influencing subsequent rat behavior.

[0078] (4) Tail suspension test Each group of rats was fixed to the edge of a table with a tail clip and secured with tape at 1 / 3 of the distance from the tail tip. The test lasted for 6 minutes, and the immobility time was measured and analyzed in the last 4 minutes.

[0079] (5) Water maze experiment A water maze system consisting of a swimming pool (150 cm in diameter, 50 cm high) and a platform (10 cm in diameter, 20 cm high) filled with 21 cm of water was used. The swimming pool was divided into four quadrants, and the platform was fixed in the fourth quadrant. The water maze experiment was conducted in two main phases: orientation navigation and spatial exploration. Orientation navigation experiment: This test assesses the rat's ability to learn the platform's location. Training was conducted continuously for 5 days. Training was conducted four times in each time period, with the rat being placed in the water from each of the four quadrants. If the rat climbed onto the platform within 90 seconds and remained there for more than 3 seconds, it was considered to have found the platform; this was the escape latency period. If the rat failed to find the platform within 90 seconds, it was guided to the platform for 10 seconds to familiarize itself with it; the latency period in this case was calculated as 90 seconds. The interval between each training session was 5 minutes. The average latency period in each of the four directions for each time period was calculated as the swimming result for that day. Spatial exploration experiment: This experiment primarily tested the rat's ability to remember the platform's spatial location after learning to find it. On the morning of day 6 of the water maze experiment, the platform was removed, and rats were placed in the water at any point. The number of times the rats crossed the quadrant where the platform was located and the number of times they crossed the original platform area within 90 seconds was observed and recorded.

[0080] (6) Echocardiography to detect cardiac function Rats in each group were anesthetized by intraperitoneal injection of 0.3% sodium pentobarbital solution at a dose of 10 mL / kg, followed by hair removal on the anterior chest. The rats were fixed in a supine position, and testing was performed after the heart rhythm stabilized. A high-resolution small animal ultrasound imaging system was used, with the probe placed on the long axis plane at the level of the papillary muscles, at a frequency of 17.5 MHz in M-mode. Heart rate and cardiac function parameters were measured, including left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), stroke volume (SV), ventricular remodeling parameters including left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs), and ventricular wall thickness parameters including left ventricular posterior wall diastolic thickness (LVPWs) and left ventricular posterior wall systolic thickness (LVPWs), etc. All parameters were measured continuously for three cardiac cycles.

[0081] (7) HE staining and Masson staining of cardiac tissue After sacrifice, the hearts of rats in each group were quickly removed, and the myocardial tissue was longitudinally sectioned, fixed in 4% paraformaldehyde for 24 hours, then dehydrated in a gradient of alcohols, cleared in xylene, and then embedded in paraffin. The tissue was cut into 10 μm sections. One portion underwent dewaxing, hydration, hematoxylin staining, differentiation, eosin staining, and dehydration, then was placed in xylene for 2 minutes and mounted with neutral resin. Another portion underwent dewaxing, hydration, hematoxylin staining, differentiation, reverse blue staining, Ponceau S and Fuchsin staining, phosphomolybdic acid staining, aniline blue staining, dehydration, and mounting. HE staining was used to observe the morphological characteristics of myocardial injury, and Masson staining was used to observe the degree of myocardial fibrosis.

[0082] (8) HE staining and Nissl body staining of brain tissue After sacrifice, the brains of mice in each group were quickly removed. Paraffin sections of the brain tissue were dewaxed and hydrated, then immersed in Nissl stain for 5 minutes, washed with water, differentiated with 0.1% glacial acetic acid, washed with water, dried in an oven, cleared with xylene for 10 minutes, and mounted. Pathological morphological changes in the CA1 region of the hippocampus of rats in each group were observed under a light microscope. (The repetition of the first paragraph is likely an error in the original text.)

[0083] (9) Detection of expression of mitochondrial autophagy-related proteins in myocardial and brain tissues 50 mg of rat myocardial and brain tissue were excised and placed in grinding tubes. 500 μL of tissue lysis buffer containing PMSF, protease inhibitors, and phosphatase inhibitors was added. The mixture was ground in a cryogenic grinder at -20°C, followed by centrifugation at 12000 r / min for 10 min at 4°C. The supernatant was the total protein of the tissue. Protein quantification was performed using the BCA method. Tissue lysis buffer was added to adjust the protein concentration, and loading buffer was added at a 4:1 ratio. The mixture was then denatured by boiling in a metal bath at 95°C for 10 min. The upper gel was subjected to electrophoresis at 70V for 30 min, the lower gel at 120V for 90 min, and electrophoresis at 250 mA on ice for 1 h. The mixture was then transferred to a PVDF membrane and blocked with 5% skim milk powder at room temperature for 2 h. The membrane was blocked overnight at 4°C with primary antibodies GADPH (1:5000), Beclin1 (1:5000), HIF-1α (1:1000), and BNIP3 (1:10000). The primary antibodies were recovered the next day, and the membrane was washed three times with PBST for 10 min each time. It was then incubated at room temperature with goat anti-rabbit / mouse secondary antibody (1:10000) for 1 h, followed by three washes with PBST for 5 min each time. The membrane was then developed and imaged using a gel imaging system, and the gray values ​​of each band were analyzed using ImageJ. Protein expression levels were expressed as target protein / GADPH.

[0084] (10) Statistical processing All experimental data are expressed as mean ± standard deviation (x ± s). If the data in each group conform to a normal distribution and have homogeneity of variance, a one-way ANOVA is used. P < 0.05 is considered statistically significant.

[0085] 2.3 Results (1) Effect of Dan Gui Shu Xin Jie Yu Formula on body weight of rats with myocardial ischemia and depression Compared with the blank control group, the body weight gain of rats in the model group was significantly decreased on days 15, 30, and 45 (P < 0.01). Compared with the model group, the body weight of rats in the high-dose group and the positive control group was significantly increased on day 15 (P < 0.05 or P < 0.01). Compared with the model group, the body weight of rats in the positive control group was significantly increased on day 30 (P < 0.01). Compared with the model group, the body weight of rats in the high-dose group and the positive control group was also significantly increased on day 45 (P < 0.01). See Figure 18 .

[0086] (2) Effects of Dan Gui Shu Xin Jie Yu Formula on the sucrose preference, tail suspension test, water maze test, and spatial exploration behavior of mice with myocardial ischemia and depression Compared with the blank control group, the sucrose preference of rats in the model group was significantly reduced (P < 0.01). Compared with the model group, the sucrose preference of rats in the high-dose and low-dose groups of Dangui Shuxin Jieyu Formula was significantly increased (P < 0.05), and the sucrose preference of rats in the positive control group was also significantly increased (P < 0.01). See Figure 19 and Figure 20 .

[0087] Compared with the blank control group, the resting time of rats in the model group was significantly increased (P < 0.01). Compared with the model group, the resting time of rats in the high-dose Dangui Shuxin Jieyu Formula and the positive control group was significantly shortened (P < 0.05). See Figure 21 and Figure 22 .

[0088] Compared with the blank control group, the total distance, central region distance, and central latency of rats in the model group were significantly decreased (P < 0.01). Compared with the model group, the total distance, central region distance, and central latency of rats in the positive control group were significantly increased (P < 0.01). Meanwhile, the total distance of rats in the high-dose Dangui Shuxin Jieyu Fang group was significantly increased (P < 0.05). See Figure 23 and Figure 24 .

[0089] In the water maze experiment, during the navigation tests from day 1 to 5, the escape latency of mice in all groups shortened with increasing training time. Compared with the blank control group, the escape latency of rats in the model group was prolonged on days 1, 2, 3, 4, and 5, which was statistically significant (P < 0.05 or P < 0.01). Compared with the model group, the escape latency of rats in the high-dose group of Dan Gui Shu Xin Jie Yu Fang was significantly shortened on days 2, 3, 4, and 5 (P < 0.05 or P < 0.01). Simultaneously, the escape latency of rats in the positive control group was also significantly shortened on days 2-5 (P < 0.05 or P < 0.01). In the 5-day spatial exploration experiment, compared with the blank control group, the number of platform crossings and target quadrant crossings of rats in the model group were significantly reduced (P < 0.05 or P < 0.01). Compared with the model group, the number of times rats in the high-dose group of Dangui Shuxin Jieyu Formula and the positive control group crossed the target quadrant was significantly increased, which was statistically significant (P < 0.05). See Figure 25-28 .

[0090] (3) Effects of Dan Gui Shu Xin Jie Yu Formula on cardiac function in rats with myocardial ischemia and depression Compared with the blank control group, the cardiac EF, FS, SV, CO, LVAW;s, and LVAW;d of rats in the model group were significantly decreased (P < 0.01). Compared with the model group, the cardiac EF, FS, SV, CO, LVAW;s, and LVAW;d of rats in the high-dose Dangui Shuxin Jieyu Fang group were all increased to some extent (P < 0.05 or P < 0.01); at the same time, the cardiac EF, FS, and SV of rats in the low-dose Dangui Shuxin Jieyu Fang group were also increased to some extent (P < 0.05); while only SV of rats in the positive control group showed an increase to some extent (P < 0.05). Figures 29-31 .

[0091] (4) Effects of Dan Gui Shu Xin Jie Yu Formula on Myocardial Tissue Injury in Rats with Myocardial Ischemia and Depression HE staining of myocardial tissue showed that in the blank control group, myocardial fibers were pink, with regular cell arrangement, moderate intercellular spaces, intact cell membranes, and clearly stained nuclei. In the model group, myocardial fibers were broken, cells were disordered, interstitial edema was observed, neutrophil infiltration was present, and an inflammatory response was observed. Myocardial damage was improved to some extent in both the Dan Gui Shu Xin Jie Yu formula group and the positive control group. (See...) Figure 32 (Upper part).

[0092] Masson staining showed that the number of collagen fibers between cardiomyocytes in the blank control group was relatively low, while the number of collagen fibers in the myocardial interstitium of the model group was increased and their arrangement was disordered. Necrotic myocardial fibers were replaced by blue collagen fibers. The number of myocardial collagen fibers in the high-dose Dan Gui Shu Xin Jie Yu Fang group was reduced, while the number of myocardial collagen fibers in the positive control group was similar to that in the model group. See Figure 32 (Lower half) and Figure 33 .

[0093] (5) Effects of Dan Gui Shu Xin Jie Yu Formula on pathological damage in the CA1 region of the hippocampus in rats with myocardial ischemia and depression HE staining of the CA1 region of the hippocampus in rats showed that the CA1 region of the hippocampus in the blank control group had clear structural layers, orderly cell arrangement, and regular shape. In the model group, the number of granule cells and pyramidal cells in the hippocampus of rats was significantly reduced, neuronal lesions were observed, and abnormal proliferation of glial cells was visible. Damage to the CA1 region of the hippocampus in rats in the high- and low-dose groups of Dan Gui Shu Xin Jie Yu Fang and the positive control group was improved to some extent. (See...) Figure 34 (Upper part).

[0094] Nissl staining showed that in the blank control group, neurons in the CA1 region of the hippocampus of rats were arranged regularly and compactly, with clearly distinguishable Nissl bodies. In the model group, the number of damaged neurons in the CA1 region of the hippocampus of rats increased, showing an irregular and sparse distribution, and Nissl bodies decreased, disintegrated, or disappeared. The distribution of neurons in the CA1 region of the hippocampus of rats in the high- and low-dose groups of Dan Gui Shu Xin Jie Yu Fang and the positive control group was improved compared to the model group, with a reduction in damaged neurons. (See...) Figure 34 (Lower half).

[0095] (6) Effects of Dan Gui Shu Xin Jie Yu Formula on the expression of mitochondrial autophagy-related proteins in the myocardium and brain tissue of rats with myocardial ischemia and depression In myocardial tissue, compared with the blank control group, the expression of HIF-1α, BNIP3, Beclin1, and LC3II / LC3I was significantly increased in the model group, while the expression of P62 was significantly decreased, which was statistically significant (P < 0.05 or P < 0.01). Compared with the model group, the expression of HIF-1α, BNIP3, and the LC3II / LC3I ratio in the myocardium of the high-dose Dangui Shuxin Jieyu Fang group was significantly decreased (P < 0.05). See Table 35 and... Figure 36 .

[0096] In the hippocampus of rats in the model group, compared with the blank control group, the expression levels of HIF-1α, BNIP3, and Beclin1 proteins and the LC3Ⅱ / LC3Ⅰ ratio were significantly increased (P<0.05), while the expression of P62 protein was significantly decreased (P<0.05). Compared with the model group, the high-dose group of Dangui Shuxin Jieyu Fang showed significantly decreased expression of HIF-1α, BNIP3, and Beclin1 and the LC3Ⅱ / LC3Ⅰ ratio, while the expression of P62 was increased (P<0.05 or P<0.01). Meanwhile, the low-dose group of Dangui Shuxin Jieyu Fang showed significantly decreased expression of HIF-1α and the LC3Ⅱ / LC3Ⅰ ratio, while the expression of P62 was increased. These differences were statistically significant (P<0.05 or P<0.01). See Table 37 and... Figure 38 .

[0097] 3. Effects of Acanthopanax senticosin in Dan Gui Shu Xin Jie Yu Formula on ischemia of cardiomyocytes and neurons. 3.1 Materials (1) Cells: Rat H9c2 cardiomyocytes and human neuroblastoma cells SH-SY5Y were purchased from Wuhan Pronosei Biotechnology Co., Ltd., with batch numbers CL-0089 and CL-0208, respectively. They were used in experiments after being passaged to the 4th generation. (2) Drugs and reagents Eleutheroside (ELE) (MCE Inc., USA, 39432-56-9); Na2S2O4 (Shanghai Maclean Biotechnology Co., Ltd., S818055-500g); DMEM high-glucose medium (Wuhan Sewell, G4512-500ML); H9c2 (2-1) cell culture medium (Wuhan Pronosei Biotechnology Co., Ltd., CL-0089-CM); Mitochondrial membrane potential assay kit (Solepro, M8650); Phosphate-buffered saline (PBS) (Wuhan Sewell, G4202-500ML); Cy3 fluorescent secondary antibody enhanced cell proliferation activity assay-8 (CCK-8) kit (Wuhan Sewell, G1613-5ML); Bovine serum total protein (BSA) (Wuhan Sewell, GC305010-25g); 0.25% trypsin digestion solution (Wuhan Sewell, G4010-100ML) (3) Instruments LDZX-30KB Clean Bench, Suzhou Jingantai Air Technology Co., Ltd.; BX-53 Upright Optical Microscope Acquisition System, Olympus Corporation, Japan; Incucyte Real-Time Live Cell Analysis System, Sartorius, Germany; 371 CO2 Incubator, Thermo Fisher Scientific, USA.

[0098] 3.2 Methods (1) Cell culture H9c2 and SH-SY5Y cells were cultured in DMEM high-glucose medium containing 10% FBS and grew normally in an incubator at 37 ℃ and 5% CO2. The culture medium was changed every 2 days. When the cells grew to 75%–85%, they were digested with 0.25% trypsin and then passaged or used for subsequent experiments.

[0099] (2) Establishment of the hypoxia model Weigh an appropriate amount of Na2S2O4 and dissolve it in DMED high-glucose medium, then dilute it to 50, 40, 30, 25, 20, 15, 10, and 5 mmol / L. H9c2 cells and SH-SY5Y cells were routinely cultured and then resuspended by 0.25% trypsin, diluted to 1 x 10⁵ cells per mL, and evenly seeded into 96-well plates. After 24 h, the original culture medium was aspirated and replaced with Na2S2O4-containing culture medium, 100 μL per well. The plates were then placed in an Incucyte real-time live cell analysis system and cultured for 6 h, 12 h, 24 h, and 48 h, respectively. Cell status was recorded every 2 h under a 100x optical microscope. After the time was up, the cells were removed, the Na2S2O4-containing culture medium was aspirated, and the cells were washed three times with PBS before cell viability was determined using the CCK-8 assay.

[0100] (3) Cell grouping and treatment Accurately weigh an appropriate amount of Acanthopanax senticosin and dissolve it in DMSO to prepare a stock solution with a final concentration of 1 mmol / mL. Add DMEM high-glucose medium, repeatedly pipet and let stand for about 30 min until the solution is completely clear. Filter the solution through a 0.22 μm filter membrane for sterilization. Adjust the density of H9c2 cells and SH-SY5Y cells to 1x105 / ml, and seed them into 96-well culture plates at 100 μL per well, with 6 replicates. After culturing for 24 h, treat the cells with different concentrations of drug-containing medium for 24 h. Then, use the CCK-8 assay to detect cell viability.

[0101] Both H9c2 and SH SY5Y cells were divided into 7 groups: control group, model group, low-dose eleutheroside group (ELE-L, 25 μmol / mL), medium-dose eleutheroside group (ELE-M, 50 μmol / mL), and high-dose eleutheroside group (ELE-H, 100 μmol / mL). Each treatment group was cultured in high-glucose DMEM medium containing the corresponding drug concentration for 24 h. Subsequently, except for the control group which continued to be cultured in high-glucose DMEM, the other groups were cultured in high-glucose DMEM containing Na2S2O4 for another 24 h to establish the injury model; the Na2S2O4 concentration for H9c2 cells was 30 mmol / L, and for SH SY5Y cells it was 40 mmol / L.

[0102] (4) Cell proliferation rate detection Cells were seeded in 96-well culture plates and incubated at 37 °C in a 5% CO2 incubator with 10 μL of CCK-8 solution. The optical density (OD) value at 450 nm was measured. Cell proliferation rate (%) = (OD value of each experiment - OD value of normal group) / (OD value of control group - OD value of normal group) × 100%.

[0103] (5) Statistical methods All experimental data are expressed as mean ± standard deviation (X ± s). If the data of each group conform to a normal distribution and have homogeneity of variance, a one-way ANOVA is used. P < 0.05 is considered statistically significant.

[0104] 3.3 Results (1) Determination of modeling concentration and time After H9c2 cells were stimulated with Na2S2O4, cell viability was assessed using a CCK8 assay, and the IC50 value was calculated. The IC50 value of Na2S2O4 gradually decreased over time. Figure 39 (Part a) The IC50 values ​​at 6 h and 12 h were too high, and the cell adhesion was poor at 48 h. The cell viability was around 55% at a Na2S2O4 concentration of 30 mmol / L. Figure 39 Part b), combined with changes in cell confluence ( Figure 39 (Part c) , 30 mmol / L, 24h were selected as the conditions for inducing hypoxia model.

[0105] After SH-SY5Y cells were used to induce a hypoxia model using Na2S2O4 stimulation, cell viability was assessed using CCK8, and the IC50 value was calculated to be around 52 mM. At Na2S2O4 concentrations of 20 mmol / L and 40 mmol / L, some cells showed shrinkage and morphological changes; at 60 mmol / L, cell shrinkage was significant, and cell adhesion was poor; at 80 mmol / L, most cells lost viability. Based on cell morphology, cell confluence, and CCK8 results, 40 mmol / L for 24 h was selected as the condition for inducing the hypoxia model. (See...) Figure 40 ).

[0106] 3.3 Effects of Acanthopanax senticosin on Na2S2O4-induced hypoxia in H9c2 and SH-SY5Y cells Compared with the blank control group (H9c2 cells), the cell viability of the model group was significantly reduced (P < 0.01). Compared with the model group, the cell viability after pretreatment with eleutheroside was improved to some extent, with the high-dose eleutheroside group showing the most significant improvement (P < 0.01). Incucyte observation of changes in cell confluence revealed that eleutheroside pretreatment significantly improved cell viability and cell confluence in a dose-dependent manner, with the high-dose eleutheroside powder group showing the most significant effect. Cell confluence was significantly improved in the high-dose eleutheroside group after 6 h. (See...) Figure 41 .

[0107] Compared with the blank control group (SH-SY5Y cells), the cell viability in the model group was significantly decreased (P < 0.01), and the cell confluence was significantly lower than that in the normal group. After intervention with eleutheroside, the cell viability significantly increased (P < 0.01), and the cell confluence improved. See... Figure 42 .

[0108] Traditional Chinese medicine (TCM) classifies coronary heart disease under the category of "chest pain and heart pain," primarily affecting the heart and involving the liver, spleen, and lungs. Pain arises from obstruction of the heart vessels. The main pathogenesis involves deficiency of vital energy and blood stasis, phlegm and blood stasis accumulation, internal generation of blood stasis and toxins, wind-phlegm obstruction, and liver qi stagnation. Clinical epidemiological cross-sectional studies have found that the most frequent syndromes are blood stasis (68.0%) and phlegm turbidity (61.3%), followed by qi deficiency (48.3%), qi stagnation (36.7%), and internal toxins (23.7%). Therefore, treatment often involves methods to invigorate qi and promote blood circulation, resolve phlegm and remove blood stasis, invigorate blood and detoxify, dispel wind and eliminate phlegm, and soothe the liver and regulate qi.

[0109] Depressive disorder is a mood disorder caused by various factors, characterized primarily by significant and persistent low mood. Patients typically experience emotions such as depression, anxiety, sadness, fear, or anger, and the recurrence of the condition is often related to mood fluctuations caused by various factors. Clinically, the pathogenesis is mainly classified into: deficiency of heart and gallbladder qi, liver stagnation and spleen deficiency, liver stagnation and kidney deficiency, deficiency of both heart and spleen, damp-heat in the liver and gallbladder, and disharmony between the heart and kidneys. The main traditional Chinese medicine formulas used are: formulas for tonifying the heart and warming the gallbladder to calm the nerves, formulas for soothing the liver and strengthening the spleen to relieve depression, formulas for nourishing the kidneys and calming the liver to relieve depression, formulas for nourishing the heart and strengthening the spleen to invigorate the body, formulas for nourishing the heart and strengthening the spleen to calm the mind, formulas for clearing the liver and gallbladder to relieve irritability, and formulas for harmonizing the heart and kidneys to relieve irritability.

[0110] Research on the comorbidity of coronary heart disease and depression has gradually increased over the past decade. Previously, the correlation between coronary heart disease and anxiety / depression received less attention, and they were often treated and studied as two separate diseases in clinical practice and research. In the last ten years, this field has received more attention, with a significant increase in publications, showing an upward trend. Research on coronary heart disease, as one of the most common cardiovascular diseases, and its association with negative psychological states such as anxiety and depression has gained increasing attention. Numerous epidemiological surveys also show a high incidence of coronary heart disease combined with anxiety and depression, which can adversely affect the long-term prognosis of patients. Currently, research focuses on the syndromes of qi stagnation and blood stasis, qi deficiency and blood stasis, and treatment methods and corresponding prescriptions such as soothing the liver and relieving depression, regulating qi, eliminating phlegm and turbidity, and resolving phlegm and removing blood stasis. Common syndrome elements include qi stagnation, blood stasis, qi deficiency, heat, and phlegm-dampness, primarily involving the heart and liver, but also related to the spleen, gallbladder, and kidneys. The main formulas studied in this field are Chaihu Longgu Muli Tang and Shuangxin Fang. Both formulas have certain effects on improving patients' symptoms and quality of life, as well as on serum inflammatory factors and related signaling pathways.

[0111] While there are approaches to combined interventions in the field of coronary heart disease and depression, a comorbid condition, existing technologies have not established a specific combination of ten traditional Chinese medicines centered around "promoting Yang and relieving depression, and regulating both hearts and minds." Furthermore, existing technologies have not demonstrated that this combination simultaneously improves cardiac function and depressive behavior, or links it to the HIF-1α / BNIP3-related autophagy pathway. Even though existing technologies know that Danshen, ginseng, Cyperus rotundus, and Curcuma longa have blood-activating, Qi-tonifying, and depression-relieving effects respectively, it is difficult for those skilled in the art to foresee that combining Danshen, ginseng, Ligusticum chuanxiong, Trichosanthes kirilowii, Paeonia lactiflora, Cyperus rotundus, Curcuma longa, Acanthopanax senticosus, Morinda officinalis, and Cinnamomum cassia in the proportions of this invention can simultaneously improve indicators related to cardiac systolic or diastolic function and behavioral indicators such as sucrose preference, tail suspension test, and water maze in a model of myocardial ischemia combined with depression, inhibit damage to myocardial tissue and hippocampal tissue, and regulate abnormal autophagy mediated by HIF-1α / BNIP3.

[0112] This article uses specific examples to illustrate the inventive concept in detail. The description of the above embodiments is only for the purpose of helping to understand the core idea of ​​the present invention. It should be noted that any obvious modifications, equivalent substitutions or other improvements made by those skilled in the art without departing from the inventive concept should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating coronary heart disease and depression, characterized in that, The ingredients are as follows by weight: 10-15 parts of Salvia miltiorrhiza; 8-12 parts of Panax ginseng; 8-12 parts of Ligusticum chuanxiong; 8-12 parts of Trichosanthes kirilowii; 8-12 parts of Paeonia lactiflora; 6-10 parts of Cyperus rotundus; 6-10 parts of Curcuma longa; 8-12 parts of Acanthopanax senticosus; 6-10 parts of Morinda officinalis; and 4-8 parts of Cinnamomum cassia.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition comprises, by weight, the following: Salvia miltiorrhiza 12 parts, ginseng 10 parts, Ligusticum chuanxiong 10 parts, Trichosanthes kirilowii 10 parts, Paeonia lactiflora 10 parts, Cyperus rotundus 8 parts, Curcuma longa 8 parts, Acanthopanax senticosus 10 parts, Morinda officinalis 8 parts, Cinnamomum cassia 6 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition comprises, by weight, the following: Salvia miltiorrhiza 10 parts, ginseng 12 parts, Ligusticum chuanxiong 8 parts, Trichosanthes kirilowii 12 parts, Paeonia lactiflora 8 parts, Cyperus rotundus 10 parts, Curcuma longa 6 parts, Acanthopanax senticosus 12 parts, Morinda officinalis 6 parts, Cinnamomum cassia 8 parts.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition comprises, by weight, the following: Salvia miltiorrhiza 15 parts, ginseng 8 parts, Ligusticum chuanxiong 12 parts, Trichosanthes kirilowii 8 parts, Paeonia lactiflora 12 parts, Cyperus rotundus 6 parts, Curcuma longa 10 parts, Acanthopanax senticosus 8 parts, Morinda officinalis 10 parts, Cinnamomum cassia 4 parts.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition comprises, by weight, the following: Ginseng 10 parts, Salvia miltiorrhiza 10 parts, Ligusticum chuanxiong 10 parts, Trichosanthes kirilowii 10 parts, Paeonia lactiflora 10 parts, Cyperus rotundus 8 parts, Curcuma longa 8 parts, Acanthopanax senticosus 10 parts, Morinda officinalis 8 parts, Cinnamomum cassia 6 parts.

6. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a drug for treating coronary heart disease and depression.

7. The application according to claim 6, characterized in that, The aforementioned coronary artery disease depression includes at least one of the following symptoms: Coronary heart disease complicated with mild to moderate depression; Depression following percutaneous coronary intervention (PCI) for coronary artery disease; Depression following coronary artery bypass grafting; Depression following medication treatment for coronary heart disease; Depression complicated by heart failure, including heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF). Ischemic heart disease accompanied by depressive-like symptoms.

8. The application according to claim 6, wherein the treatment of coronary heart disease with depression includes dual indicators for improving cardiac function and depressive-like behavior.

9. The application according to claim 8, characterized in that, Indicators for improving cardiac function include: increasing left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and the E' / A' ratio, and reducing myocardial damage and myocardial fibrosis; indicators for improving depressive-like behavior include improving cognitive impairment and reducing neuronal damage in the CA1 region of the hippocampus.

10. The application according to claim 6, characterized in that, The drug exerts its therapeutic effect by regulating HIF-1α / BNIP3-mediated mitochondrial autophagy in cardiomyocytes and neurons.

11. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that, include: The preparation method of the decoction includes the following steps: (1) Weigh each Chinese medicinal material according to the proportion of the Chinese medicine composition according to claim 1, and clean and crush them appropriately; (2) First decoction: Add 3 times the weight of drinking water (about 500 mL) to the herbs, soak for 30 minutes, then heat to boiling, turn to low heat and keep simmering for 30 minutes, filter and collect the filtrate; (3) Second decoction: Add 3 times the weight of drinking water (about 500 mL) to the dregs again, heat to boiling in the same way, then turn to simmer for 30 minutes, filter and collect the filtrate; (4) Combine the filtrates obtained in steps (2) and (3), and concentrate them by heating over a low flame to finally prepare a decoction with a total volume of 100 mL, which is the decoction of the Chinese herbal composition of the present invention; The method for preparing granules includes the following steps: (1) Extraction of Dan Gui Shu Xin Jie Yu Fang extract: The Chinese herbal composition according to claim 1 is soaked in 8-10 times the amount of water for 30 minutes, boiled over high heat, then simmered over low heat for 1 hour, filtered, and the residue is boiled in 4-6 times the amount of water for 1 hour, filtered, the two decoctions are combined, and heated and concentrated into a thick extract. (2) Granule preparation: The above thick extract is granulated by adding dried sugar powder and dextrin to form a block. The dry extract is obtained by drying at room temperature or low temperature. Then it is pulverized into fine powder, sugar powder and dextrin are added and mixed thoroughly. Ethanol is added as a wetting agent, mixed thoroughly, and then granulated, dried and sized to obtain Dan Gui Shu Xin Jie Yu Fang granules.

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