Traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 15 to 25 parts of radix salviae miltiorrhizae and 15 to 25 parts of radix ginseng rubra according to a weight ratio of 1 to 1. Based on the traditional Chinese medicine theory of tonifying qi, activating blood, detoxifying and dredging collaterals, the traditional Chinese medicine composition is provided for the first time to inhibit neutrophil extracellular traps (NETosis) and inflammatory response in a targeted manner, so as to prevent and treat cardiotoxicity caused by anthracycline drugs. Animal experiments show that the traditional Chinese medicine composition can remarkably improve the heart function, relieve myocardial damage and inhibit release of inflammatory factors, and has good safety. Clinical cases prove that the traditional Chinese medicine can effectively relieve symptoms of patients and guarantee smooth chemotherapy. The invention provides a brand-new, effective and safe traditional Chinese medicine treatment scheme for preventing and treating anthracycline cardiotoxicity.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines, its preparation method, and its application. Background Technology

[0002] Anthracyclines, such as doxorubicin (Arubicin), epirubicin, and daunorubicin, are first-line chemotherapy drugs for the clinical treatment of malignant tumors such as breast cancer, leukemia, and lymphoma. However, their severe anthracycline-induced cardiotoxicity (AIC) is a major obstacle limiting their clinical application. AIC can manifest as acute, chronic, or delayed reactions. Acute cardiotoxicity can occur shortly after administration, manifesting as arrhythmias and myocardial cell damage, which not only affects the chemotherapy process but may even lead to death.

[0003] Currently, clinical strategies for preventing and treating acute inflammatory disease (AIC) are very limited. Dexrazoxane is the only widely used chemoprotective agent, but it has significant side effects such as high cost, bone marrow suppression, and potential liver and kidney damage. Furthermore, its mechanism of action is mainly focused on mitigating the direct toxicity of anthracyclines, and it is insufficient in addressing the crucial immune inflammatory processes in the development of AIC, particularly the abnormal activation of neutrophils and the formation of neutrophil NETosis. Other treatments, such as angiotensin-converting enzyme inhibitors (ACEIs) or beta-blockers, have some effect, but their broad target range lacks precision, resulting in unsatisfactory preventative effects and potential side effects such as hypotension and bradycardia.

[0004] Therefore, developing a traditional Chinese medicine composition that can accurately target the core mechanism of AIC, is safe, effective, and economical is of great clinical significance. Summary of the Invention

[0005] Based on this, the purpose of this invention is to provide a traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines, its preparation method and application, which effectively alleviates cardiotoxicity by targeting neutrophil function, inhibiting NETosis and inflammatory response, and is safe and inexpensive.

[0006] To achieve the above objectives, the present invention adopts the following technical solution.

[0007] This invention provides a traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracycline drugs, wherein the traditional Chinese medicine composition is composed of danshen and red ginseng in a weight ratio of 1:1.

[0008] In some embodiments of the present invention, the traditional Chinese medicine combination includes the following raw materials in parts by weight: 15-25 parts of Salvia miltiorrhiza and 15-25 parts of red ginseng.

[0009] In some embodiments of the present invention, the traditional Chinese medicine combination includes the following raw materials in parts by weight: 20 parts of Salvia miltiorrhiza and 20 parts of red ginseng.

[0010] The present invention also discloses a method for preparing the traditional Chinese medicine composition, comprising: taking the raw materials of the traditional Chinese medicine composition according to the formula, extracting with water, and collecting the extract to obtain the final product.

[0011] In some embodiments of the present invention, the water extraction includes decoction extraction, which is carried out twice. The first decoction is carried out with 8 times the amount of water for 2 hours, and the second decoction is carried out with 6 times the amount of water for 2 hours. The filtrates from the two decoctions are then combined.

[0012] The present invention also discloses a drug for preventing and treating the cardiotoxicity of anthracyclines, wherein the drug uses the aforementioned traditional Chinese medicine composition as its active ingredient.

[0013] In some embodiments of the present invention, the drug further includes pharmaceutically acceptable excipients.

[0014] In some embodiments of the present invention, the pharmaceutically acceptable excipients include at least one of binders, fillers, diluents, lubricants, disintegrants, colorants, flavorings, humectants, suspending agents, emulsifiers, and preservatives.

[0015] In some embodiments of the present invention, the dosage form of the drug is a decoction, granules, pills, capsules, tablets, powders, or oral liquid.

[0016] The present invention also discloses the use of the traditional Chinese medicine composition in the preparation of a medicament for the prevention or treatment of anthracycline-induced cardiotoxicity.

[0017] In some embodiments of the present invention, the cardiotoxicity is acute cardiotoxicity, the symptoms of which include one or more of myocardial injury, decreased cardiac function, arrhythmia, or NETosis of neutrophils; the anthracycline drug is doxorubicin, epirubicin, or daunorubicin.

[0018] The traditional Chinese medicine composition described in this invention consists of two herbs, Danshen and Red Ginseng. It is the first to propose targeted intervention to precisely regulate neutrophil function and make up for the shortcomings of existing drugs in general regulation. The traditional Chinese medicine composition of this invention is original. Danshen and Red Ginseng are combined in a 1:1 ratio. Danshen (slightly cold and bitter in nature) invigorates blood and detoxifies, clears the heart and relieves irritability. Red Ginseng (warm in nature, sweet and slightly bitter) greatly replenishes vital energy, restores pulse and consolidates the body. The two herbs are used in combination to replenish qi and consolidate the body while detoxifying and removing blood stasis. Together, they have the effects of invigorating qi and blood, detoxifying and unblocking the meridians, and achieve the synergistic effect of "regulating qi and blood, detoxifying and unblocking the meridians".

[0019] Danshen, as the core ingredient of this invention, possesses significant therapeutic effects such as promoting blood circulation, removing blood stasis, anti-inflammation, and improving microcirculation. Danshen reduces neutrophil activation and alleviates inflammation by regulating immune responses, protecting the heart from the direct toxic effects of anthracyclines. Tanshinone compounds in Danshen effectively inhibit AIC-related oxidative stress and improve cardiac microcirculation, promoting cardiac repair and functional recovery. Furthermore, Danshen can enhance cardiac metabolism and repair capabilities by regulating cardiac blood flow, thereby effectively reducing the occurrence of serious complications such as heart failure.

[0020] Red ginseng is another key ingredient in this invention, possessing a wide range of pharmacological effects, particularly in antioxidation, anti-inflammation, and immunomodulation. Red ginseng can alleviate cardiac damage caused by anthracyclines by inhibiting oxidative stress, enhancing antioxidant enzyme activity, and improving microcirculation. It can also regulate the immune system, reducing excessive immune response damage to the heart and protecting cardiomyocytes. The main active ingredient in red ginseng—ginsenosides—can improve cardiac function through multiple pathways, reduce the release of inflammatory factors, and alleviate the clinical symptoms of acute cardiac infarction (AIC).

[0021] Based on the technical solution of the present invention, the present invention has the following beneficial effects compared with the prior art:

[0022] The traditional Chinese medicine composition (SST) provided in this invention for preventing and treating anthracycline-induced cardiotoxicity can effectively alleviate acute cardiac injury caused by anthracyclines and enhance the anti-apoptotic capacity of cardiomyocytes by targeting and regulating neutrophil function, inhibiting NETosis and inflammatory responses. Comprehensive analysis, including cardiac function assessment, histopathological analysis, inflammatory factor detection, and molecular mechanism studies, has confirmed the therapeutic effect of SST. This invention provides valuable insights into SST as a promising candidate for the prevention and treatment of anthracycline-induced cardiotoxicity, highlighting its potential to improve cardiac function while precisely intervening in immune-inflammatory mechanisms. Overall, SST represents a significant advancement in strategies for preventing and treating anthracycline-induced cardiotoxicity.

[0023] Verification has shown that the traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity provided by this invention can significantly improve doxorubicin (DOX)-induced cardiac function damage, reduce myocardial pathological changes and fibrosis, and inhibit neutrophil-mediated inflammatory responses.

[0024] Studies have shown that the traditional Chinese medicine composition provided by this invention can effectively alleviate symptoms such as palpitations and chest tightness in clinical applications, improve abnormal electrocardiogram findings, reduce the incidence of cardiotoxicity, and ensure the smooth progress of chemotherapy. Previous animal experiments have demonstrated that serum containing the Shuangshen Decoction can significantly inhibit cardiomyocyte apoptosis and reduce oxidative stress damage. Fluorescence staining and transcriptomics analysis revealed that SST can significantly inhibit DOX-induced cardiac inflammatory responses by regulating neutrophil NETosis. The traditional Chinese medicine composition provided by this invention has a simplified formulation, with both herbs being food-grade medicinal materials, ensuring high safety and low cost. Mass spectrometry analysis has also been performed to clearly identify the components. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 This is a graph showing the general condition of mice in different treatment groups; among them, Figure 1 In the figure, A represents the survival curves of mice in different treatment groups; Figure 1 In the graph, B represents the weight changes of mice in different treatment groups.

[0027] Figure 2 The images show the echocardiographic results of mice in different treatment groups.

[0028] Figure 3 Electrocardiographic data of mice in different treatment groups.

[0029] Figure 4 Image showing HE staining results of heart tissue from mice in different treatment groups.

[0030] Figure 5 The image shows the TUNEL staining results of heart tissue from mice in different treatment groups.

[0031] Figure 6 WGA staining images of heart tissue from mice in different treatment groups.

[0032] Figure 7 The diagram shows the effects of different treatment groups on cardiac inflammatory responses in mice; among them, Figure 7 In the figure, H represents the effect of different treatment groups on the serum inflammatory factor TNF-α level in mice; Figure 7 In the figure, I represents the effect of different treatment groups on the serum inflammatory factor IL-6 level in mice; Figure 7In Figure J, the effect of different treatment groups on the serum inflammatory factor IL-1β level is shown; in Figure J, K represents the effect of different treatment groups on the serum inflammatory factor CXCL1 level.

[0033] Figure 8 Image showing NETosis immunofluorescence staining of heart tissue from mice in different treatment groups.

[0034] Figure 9 A diagram illustrating the molecular mechanism by which SST improves acute cardiotoxicity of DOX; among which, Figure 9 M in the graph represents the gene clustering heatmap; Figure 9 N in the figure represents the GSEA enrichment plot. Detailed Implementation

[0035] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the embodiments thereof. 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 protection scope of the present invention.

[0036] The following description is based on specific embodiments.

[0037] Experimental materials: The Chinese herbal raw materials used in this invention, Danshen and red ginseng, were purchased from the First Affiliated Hospital of Guangzhou University of Chinese Medicine and stored in a sealed, light-proof, and cool place.

[0038] Example 1: A traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity and its preparation method

[0039] A traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines, comprising 20g of Danshen (Salvia miltiorrhiza) and 20g of red ginseng.

[0040] A method for preparing a traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines: the preparation is carried out by decoction.

[0041] Weigh the above-mentioned raw materials according to weight, soak the raw materials in water for 30 minutes, and then decoct them twice: add 8 times the amount of water for the first time and 6 times the amount of water for the second time. Each decoction time is 2 hours. After decoction, combine the filtrates from the two decoctions to obtain the Chinese medicine composition, which is named Shuangshen Decoction.

[0042] Example 2: A traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity and its preparation method

[0043] A traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines, comprising 15g of Salvia miltiorrhiza and 15g of red ginseng.

[0044] A method for preparing a traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines: the preparation is carried out by decoction.

[0045] Weigh the above-mentioned raw materials according to weight, soak the raw materials in water for 30 minutes, and then decoct them twice: add 8 times the amount of water for the first time and 6 times the amount of water for the second time. Each decoction time is 2 hours. After decoction, combine the filtrates from the two decoctions to obtain the Chinese medicine composition, which is named Shuangshen Decoction.

[0046] Example 3: A traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity and its preparation method

[0047] A traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines, comprising 25g of Danshen (Salvia miltiorrhiza) and 25g of red ginseng.

[0048] A method for preparing a traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines: the preparation is carried out by decoction.

[0049] Weigh the above-mentioned raw materials according to weight, soak the raw materials in water for 30 minutes, and then decoct them twice: add 8 times the amount of water for the first time and 6 times the amount of water for the second time. Each decoction time is 2 hours. After decoction, combine the filtrates from the two decoctions to obtain the Chinese medicine composition, which is named Shuangshen Decoction.

[0050] Efficacy verification of traditional Chinese medicine composition for preventing and treating anthracycline cardiotoxicity

[0051] I. Experimental Methods

[0052] The traditional Chinese medicine decoction was prepared according to the method shown in Example 1 for efficacy verification. Specifically, in order to study the therapeutic effect of the traditional Chinese medicine composition provided by the present invention on the cardiotoxicity of anthracyclines, an acute cardiotoxicity (AIC) model induced by anthracyclines (taking doxorubicin as an example) was established in mice. The mice were treated with the traditional Chinese medicine composition, and then the efficacy was evaluated and pharmacological analysis was performed.

[0053] 1. Experimental materials

[0054] Eight-week-old male SPF-grade C57BL / 6J mice (body weight 18-22g) were used. Doxorubicin (DOX) was administered. The herbal decoction of this invention (the daily dose of raw herb administered to mice by gavage was 10 g / kg / d according to the "Equivalent Dose Ratio Table of Human and Animal Body Surface Area" in "Medical Laboratory Animal Science", prepared according to Example 1, with a low, medium and high dose ratio of 1:2:4) and atorvastatin (ATV, 40 mg / kg) was used as a positive control.

[0055] 2. Establishment of animal models

[0056] Eight-week-old male SPF-grade C57BL / 6J mice (weighing 18-22g) were used to induce an acute cardiotoxicity model via a single tail vein injection of doxorubicin (DOX) after one week of acclimatization. The DOX concentration was 4 mg / ml, and the injection dose was 20 mg / kg. The normal control group (NC group) received an equal dose of physiological saline via tail vein injection. Baseline body weight was measured in all mice before modeling. After modeling, mouse body weight was monitored daily, and their mental state, food intake, fur, daily activities, defecation, and survival were observed.

[0057] 3. Grouping and Dosing

[0058] After successful modeling, mice were randomly divided into six groups: normal control group (NC group), model group (DOX group), atorvastatin (ATV group), high-dose traditional Chinese medicine composition group (SST-H group), medium-dose traditional Chinese medicine composition group (SST-M group), and low-dose traditional Chinese medicine composition group (SST-L group). Except for the NC group, which was injected with an equal volume of physiological saline, the other groups of mice were administered the corresponding doses of the drug by gavage after DOX modeling. The specific administration regimens were as follows: SST-L group was administered the low-dose traditional Chinese medicine composition (5 g / kg) by gavage, SST-M group was administered the medium-dose traditional Chinese medicine composition (10 g / kg) by gavage, SST-H group was administered the high-dose traditional Chinese medicine composition (20 g / kg) by gavage, and ATV group was administered atorvastatin (40 mg / kg) by gavage. All drug treatments began 7 days before modeling and continued until 14 days after modeling. Gavage was administered once daily, and all drugs were administered with the same volume of physiological saline.

[0059] 4. General indicator testing

[0060] During the experiment, the general condition of the mice in each group was observed and recorded daily, including their mental state, food intake, water intake, excretion, hair growth, and mortality. Their weight changes were also measured.

[0061] 5. Cardiac function assessment

[0062] On days 1 and 7 post-modeling, small animal ultrasound (echocardiography) was used to assess cardiac function in mice. Specifically, cardiac systolic function indices, including left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), were quantitatively measured using short-axis views at the papillary muscle level. These parameters were then analyzed using relevant modules.

[0063] 6. Electrocardiogram (ECG) function assessment

[0064] On day 3 post-modeling, electrocardiograms (ECGs) of mice were recorded using a small animal ECG system. Mice were anesthetized and fixed to their limbs with electrode clamps for ECG waveform recording. Measurement parameters included QTc interval, PR interval, heart rate, and QRS width. All mice underwent ECG monitoring on day 14 after the experiment. Recording time was 5-10 minutes, and waveform analysis was performed using ECG analysis software (such as LabChart). ECG changes in different groups were compared to evaluate the intervention effect of the traditional Chinese medicine composition on DOX-induced electrophysiological abnormalities.

[0065] 7. Neutrophil detection

[0066] To evaluate the effect of the traditional Chinese medicine composition on neutrophils in acute cardiotoxicity, the following methods were used: ① Neutrophil extracellular net formation (NETosis) detection: Immunofluorescence staining was used to label histone H3 (H3CIT) and MPO antibody to observe the formation of NETs in mouse heart tissue, assessing the status of neutrophil extracellular traps and their correlation with cardiac injury. ② Inflammatory factor detection: ELISA kits were used to detect serum inflammatory factors, such as TNF-α, IL-6, IL-1β, and CXCL1, to evaluate the inhibitory effect of the traditional Chinese medicine composition on the inflammatory response.

[0067] 8. Cardiac Pathological Analysis

[0068] After the experiment, all mice were over-anesthetized, and cardiac tissue was collected for pathological analysis. HE staining and WGA staining were used to examine myocardial structure and inflammatory response, and to assess cardiac damage and fibrosis.

[0069] II. Experimental Results

[0070] 1. Traditional Chinese medicine composition improves the general condition of mice with DOX acute cardiotoxicity.

[0071] After modeling, the general condition of the mice was observed. Mice in the NC group were in good condition with no deaths, glossy and smooth fur, good mental state, free movement, and continuous weight gain. Their food and water intake, as well as urination and defecation, were normal, and their bedding was dry and odorless. In contrast, mice in the DOX group were generally lethargic, with dull, yellowish fur, significantly reduced weight, decreased activity, poor appetite, damp bedding with a noticeable odor, and a higher mortality rate.

[0072] The results are as follows Figure 1 As shown in Figures A and B, compared with the DOX group, mice in the low-dose (SST-L), medium-dose (SST-M), and high-dose (SST-H) groups of the traditional Chinese medicine composition had higher body weight, lower mortality rates, and delayed death times. The results indicate that the traditional Chinese medicine composition can improve the general condition of mice with DOX-induced acute cardiotoxicity, slow weight loss, and prolong survival.

[0073] 2. Traditional Chinese medicine composition improves cardiac function in mice with acute cardiotoxicity caused by DOX.

[0074] Echocardiographic observation showed that the NC group mice had good myocardial contractile function and maintained normal left ventricular ejection fraction (LVEF); while the DOX group mice showed significantly weakened myocardial contractile function and significantly decreased LVEF, indicating impaired cardiac function. Compared with the DOX group, the low-dose group of the traditional Chinese medicine composition (SST-L) showed some improvement in cardiac function, but the effect was limited; the medium-dose group of the traditional Chinese medicine composition (SST-M) almost restored cardiac function to normal, and significantly improved LVEF; the high-dose group of the traditional Chinese medicine composition (SST-H) also showed significant improvement in cardiac function, with LVEF returning to near normal levels. The atorvastatin group (ATV) showed similar effects to the medium- and high-dose traditional Chinese medicine composition groups. Overall, the traditional Chinese medicine composition, especially the medium- and high-dose groups, significantly alleviated DOX-induced cardiotoxicity and improved cardiac function (e.g., Figure 2 (As shown).

[0075] Electrocardiogram analysis further confirmed that the QTc interval and PR duration were significantly prolonged in the DOX group mice, suggesting that doxorubicin induced electrophysiological abnormalities. In contrast, the high-dose groups (SST-M, SST-H) of the traditional Chinese medicine composition significantly shortened the QTc interval and PR duration, restoring them to near-normal levels. While the low-dose group (SST-L) showed improvement, the effect was not as significant as the medium- and high-dose groups. The atorvastatin group exhibited similar electrophysiological protective effects (e.g., ...). Figure 3 (As shown).

[0076] 3. Traditional Chinese medicine composition improves myocardial pathological damage in mice with DOX acute cardiotoxicity.

[0077] HE staining results showed that the myocardial tissue structure of mice in the NC group was normal, with neatly arranged cardiomyocytes and intact nuclei and cytoplasm. In contrast, the cardiomyocytes of mice in the DOX group were disordered, with loss of myofibrils and significant vacuolation of both the cytoplasm and nucleus, indicating severe cardiac damage. Compared with the DOX group, the myocardial damage in mice treated with the traditional Chinese medicine combination intervention groups (SST-L, SST-M, SST-H) was significantly reduced, with more intact cardiomyocyte structure and a marked improvement in the degree of damage (e.g., ...). Figure 4 (As shown).

[0078] TUNEL staining results showed that cardiomyocyte apoptosis was significantly increased in the DOX group mice, while apoptotic cells were significantly reduced in the traditional Chinese medicine combination group mice, especially in the SST-M and SST-H groups, where they almost returned to normal levels. Atorvastatin also significantly reduced cardiomyocyte apoptosis (e.g., ...). Figure 5 (As shown).

[0079] WGA staining showed that the DOX group mice had damaged cardiomyocyte membrane structure, increased intercellular spaces, and reduced cell membrane junctions. In contrast, the groups intervened with the traditional Chinese medicine composition, especially the SST-M and SST-H groups, had more intact cell membrane structures, tightly packed cells, and more WGA-positive areas, indicating that the traditional Chinese medicine composition has a positive effect on protecting cardiomyocyte membrane structure (e.g., Figure 6 (As shown).

[0080] 4. Effects of traditional Chinese medicine composition on cardiac inflammatory response in mice with DOX acute cardiotoxicity

[0081] The results are as follows Figure 7 As shown in the HK diagram, ELISA detection revealed significantly elevated levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and CXCL1 in the serum of DOX-treated mice, indicating that DOX induced a severe cardiac inflammatory response. Compared to the DOX group, the traditional Chinese medicine (TCM) composition group (SST group) showed a dose-dependent inhibitory effect on inflammatory cytokines. With increasing dosage of the TCM composition, the levels of TNF-α, IL-6, IL-1β, and CXCL1 gradually decreased, especially in the SST-M and SST-H groups, where inflammatory cytokine levels almost returned to normal. These results indicate that a medium dose of the TCM composition is most effective in inhibiting inflammatory cytokines, significantly alleviating DOX-induced cardiac inflammatory responses and demonstrating a potent protective effect.

[0082] 5. Effects of traditional Chinese medicine composition on NETosis in mice with DOX-induced acute cardiotoxicity

[0083] Observation using H3CIT and MPO dual fluorescence staining showed significantly enhanced NETosis in the myocardial tissue of DOX-group mice, with markedly enhanced H3CIT and MPO fluorescence markings, indicating strong NET formation. Compared with the DOX group, the low-dose group (SST-L) of the traditional Chinese medicine composition showed a certain inhibitory effect on NETosis; the medium-dose group (SST-M) and the high-dose group (SST-H) showed the strongest inhibitory effect, with H3CIT and MPO markings almost returning to normal levels, demonstrating the powerful effect of the traditional Chinese medicine composition in inhibiting NETosis; the atorvastatin group (ATV) also showed similar effects (e.g., Figure 8 (As shown). In summary, the traditional Chinese medicine composition, especially at medium to high doses, can significantly inhibit DOX-induced NETosis, reduce cardiac inflammatory damage, and has potential cardioprotective effects.

[0084] 6. Based on transcriptome analysis, the molecular mechanism by which a traditional Chinese medicine composition improves DOX acute cardiotoxicity in mice was discovered.

[0085] The results are as follows Figure 9As shown by M and N in the figure, by comparing the blank group, the DOX group, and the traditional Chinese medicine group, it was found that DOX significantly aggravated cardiac inflammation by upregulating inflammatory genes and downregulating protective genes (such as...). Figure 9 (As shown in M ​​in the figure). A comparison between the DOX group and the traditional Chinese medicine group revealed that the traditional Chinese medicine group could downregulate NETosis expression (e.g., M in the figure). Figure 9 (As shown in N in the diagram).

[0086] Clinical application cases

[0087] Case 1:

[0088] Patient Wu, female, 22 years old, was diagnosed with anaplastic T-cell lymphoma (ALK-positive stage III) in December 2024. She received chemotherapy with BV (brentuximab vedotin) + CHP (cyclophosphamide, doxorubicin, and dexamethasone) regimen, which included anthracyclines (doxorubicin liposome 40mg). After chemotherapy, she experienced palpitations and chest tightness, and an electrocardiogram showed a short PR interval. Traditional Chinese medicine diagnosed her with Qi deficiency and blood stasis syndrome. She was treated with a decoction prepared from the herbal composition of this invention (red ginseng 20g, danshen 20g), 250ml twice daily, taken warm in the morning and evening, for one week before and after chemotherapy. After treatment, the palpitations and chest tightness significantly decreased, and a follow-up electrocardiogram showed the short PR interval had disappeared. No liver or kidney damage or adverse drug reactions were observed.

[0089] Case 2:

[0090] Patient Zheng, male, 23 years old, was diagnosed with diffuse large B-cell lymphoma (involving the stomach, intestines, and peritoneum, stage IIE). Due to extensive tumor infiltration, surgery was not possible. On November 23, 2024, he received chemotherapy (cyclophosphamide + vincristine) containing anthracyclines (doxorubicin liposome). Pre-chemotherapy electrocardiogram showed incomplete right bundle branch block. From the first day of chemotherapy, he was treated with a traditional Chinese medicine decoction prepared from the herbal composition of this invention (20g red ginseng, 20g danshen), twice daily, 100ml concentrated decoction each time, taken warm in the morning and evening, for the entire chemotherapy cycle (8 days). He did not experience chest tightness, palpitations, or other cardiotoxic symptoms throughout the course of chemotherapy, nor did he develop new arrhythmias or worsen conduction block. He successfully completed the chemotherapy.

[0091] Case 3:

[0092] Patient Yang, female, 40 years old, was diagnosed with acute B-lymphoblastic leukemia. From July to December 2024, she received multiple rounds of intensive chemotherapy containing anthracyclines (daunorubicin, epirubicin) (DVCP / Hyper-CVAD regimen). On January 8, 2025, she developed severe myelosuppression (platelet count 19×10⁻⁶). 9 / L), but the chemotherapy regimen still needs to be continued. To prevent anthracycline cardiotoxicity, the patient was treated with a traditional Chinese medicine decoction prepared from the herbal composition of this invention (20g red ginseng, 20g salvia miltiorrhiza), twice daily, 250ml each time, taken warm in the morning and evening, for 6 consecutive days, starting from January 12, 2025. During the treatment period, no cardiotoxic symptoms such as chest tightness or palpitations occurred, and the platelet count steadily recovered to 56×10. 9 / L (January 18, 2025), to ensure the smooth progress of subsequent chemotherapy.

[0093] In summary, this invention proposes a traditional Chinese medicine composition targeting the immune mechanism of neutrophils for the prevention and treatment of acute cardiotoxicity (AIC) induced by anthracycline drugs such as doxorubicin and epirubicin. The traditional Chinese medicine composition provided by this invention significantly improves the general condition, cardiac function, and myocardial damage in DOX-induced mice; specifically, SST can reduce weight loss, prolong survival, and significantly improve cardiac function in mice. Furthermore, SST improves myocardial structural damage, inhibits cardiomyocyte hypertrophy, and improves cardiomyocyte apoptosis, thereby promoting cardiac repair. Fluorescence staining and transcriptomics analysis revealed that SST significantly inhibits DOX-induced cardiac inflammatory responses by regulating neutrophil NETosis, demonstrating greater safety and efficacy than existing treatment regimens. In clinical applications, the herbal composition of this invention has been successfully applied to multiple cases, such as patients with anaplastic T-cell lymphoma, diffuse large B-cell lymphoma, and acute B-lymphoblastic leukemia. It has significantly reduced cardiotoxicity induced by anthracycline chemotherapy, improved symptoms such as palpitations and chest tightness, restored normal electrocardiogram parameters, and ensured the smooth progress of chemotherapy. These clinical cases fully verify the significant effect of the technical solution of this invention in the prevention and treatment of acute acute leukemia (AIC), providing a novel treatment strategy for the prevention and treatment of AIC.

[0094] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0095] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A traditional Chinese medicine composition for preventing and treating the cardiotoxicity of anthracyclines, characterized in that, The traditional Chinese medicine composition consists of Danshen and Red Ginseng in a weight ratio of 1:

1.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The herbal combination includes the following raw materials in parts by weight: 15-25 parts of Salvia miltiorrhiza and 15-25 parts of red ginseng.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The herbal combination includes the following raw materials in parts by weight: 20 parts of Salvia miltiorrhiza and 20 parts of red ginseng.

4. The method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, include: Take the raw materials of the Chinese herbal medicine composition according to the formula, extract with water, and collect the extract to obtain the final product.

5. The preparation method according to claim 4, characterized in that, The water extraction includes decoction extraction, which is carried out twice. The first decoction is carried out with 8 times the amount of water for 2 hours, and the second decoction is carried out with 6 times the amount of water for 2 hours. The filtrates from the two decoctions are combined.

6. A drug for preventing and treating the cardiotoxicity of anthracyclines, characterized in that, The drug uses the traditional Chinese medicine composition according to any one of claims 1 to 3 as its active ingredient.

7. The drug as described in claim 6, characterized in that, The drug also includes pharmaceutically acceptable excipients.

8. The drug as described in claim 6, characterized in that, The dosage form of the drug is decoction, granules, pills, capsules, tablets, powders, or oral liquid.

9. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for the prevention or treatment of anthracycline-induced cardiotoxicity.

10. The application as described in claim 9, characterized in that, The cardiotoxicity is acute cardiotoxicity, the symptoms of which include one or more of myocardial damage, decreased cardiac function, arrhythmia or neutrophil extracellular trap formation; the anthracycline drug is doxorubicin, epirubicin or daunorubicin.

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