Traditional Chinese medicine composition for treating fatty liver diseases related to metabolic dysfunction and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating fatty liver diseases related to metabolic dysfunction. The traditional Chinese medicine composition is prepared from the following raw material medicines: Qu fructus aurantii, lotus leaves, semen cassiae, gynostemma pentaphylla, rhizoma alismatis, rhodiola rosea, radix salviae miltiorrhizae, pseudo-ginseng and rhizoma atractylodis macrocephalae. The traditional Chinese medicine composition and the traditional Chinese medicine compound preparation disclosed by the invention can improve the blood sugar and blood fat levels of fatty liver diseases related to metabolic dysfunction and improve the metabolic level, are remarkable in clinical curative effect, improve the living quality of patients, have the effects of regulating qi, soothing the liver, tonifying the spleen and removing stasis, slow down liver fibrosis by improving blood sugar and blood fat metabolism, and are quick in curative effect and low in price.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine compound research, and particularly relates to a traditional Chinese medicine composition for treating metabolic dysfunction-associated steatotic liver disease and its application. Background Art

[0002] Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) was renamed from Nonalcoholic fatty liver disease (NAFLD) to emphasize the extrahepatic manifestations of the disease and cardiovascular and metabolic risk factors, with blood glucose being the most critical.

[0003] In recent years, the incidence of MASLD has been increasing year by year, becoming one of the most common liver diseases globally. The large MASLD base and related extrahepatic hazards in China have become one of the major public health problems affecting China's social development. The etiology of MASLD is complex, and factors such as obesity, insulin resistance, and high-fat diet are the main risk factors for induction. Single drugs often cannot meet the treatment needs of all symptoms of MASLD. Weight loss, increased physical activity, and improved eating habits can play a role in preventing and improving MASLD, but many patients often lack the motivation to maintain these healthy habits in the long term, resulting in poor treatment compliance and inability to significantly improve the curative effect. Therefore, drug treatment needs to be appropriately given to patients with poor compliance. In 2024, the US Food and Drug Administration (FDA) announced the approval of the oral small molecule drug Rezdiffra (active ingredient resmetirom) for the treatment of metabolic dysfunction-associated steatohepatitis with moderate to advanced liver scarring. This drug has not been approved for marketing in China and is expensive. Traditional Chinese medicine has a definite curative effect on improving the symptoms of MASLD, especially for MASLD patients with abnormal glucose and lipid metabolism. Therefore, there is an urgent need in China to invent a traditional Chinese medicine composition with a similar effect to Rezdiffra and a lower price. Summary of the Invention

[0004] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating metabolic dysfunction-associated steatotic liver disease and related glucose and lipid metabolism disorders, and the formula is named Liqi Tiaozhi Fang, so as to overcome the current situation in the prior art that there is no specific drug for treating MASLD in China.

[0005] The technical solution adopted by the present invention is: A traditional Chinese medicine composition for treating metabolic dysfunction-associated steatotic liver disease, the traditional Chinese medicine composition comprising the following raw drugs: Fructus Aurantii Immaturus, Folium Nelumbinis, Semen Cassiae, Gynostemma Pentaphyllum, Rhizoma Alismatis, Rhodiola Rosea, Radix Salviae Miltiorrhizae, Radix Notoginseng, Rhizoma Atractylodis Macrocephalae.

[0006] Furthermore, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 10-15 parts of Quzhiqiao, 10-15 parts of lotus leaf, 15-20 parts of cassia seed, 10-15 parts of gynostemma pentaphyllum, 6-12 parts of alisma orientale, 6-12 parts of rhodiola rosea, 6-12 parts of salvia miltiorrhiza, 4-8 parts of notoginseng, and 4-8 parts of raw atractylodes macrocephala.

[0007] Preferably, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 10-12 parts of Quzhiqiao, 10-12 parts of lotus leaf, 16-18 parts of cassia seed, 10-12 parts of gynostemma pentaphyllum, 8-9 parts of alisma orientale, 8-9 parts of rhodiola rosea, 8-9 parts of salvia miltiorrhiza, 5-6 parts of notoginseng, and 5-6 parts of raw atractylodes macrocephala.

[0008] More preferably, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 12 parts of Quzhiqiao, 12 parts of lotus leaf, 18 parts of cassia seed, 12 parts of gynostemma pentaphyllum, 9 parts of alisma orientale, 9 parts of rhodiola rosea, 9 parts of salvia miltiorrhiza, 6 parts of notoginseng, and 6 parts of raw atractylodes macrocephala.

[0009] Metabolic dysfunction-associated fatty liver disease belongs to the categories of "Feiqi", "Blood Stasis", "Phlegm Syndrome", "Hypochondriac Pain", "Accumulation Syndrome" in traditional Chinese medicine. The pathogenesis of traditional Chinese medicine lies in the interaction of multiple factors such as "disharmony between the liver and spleen, qi stagnation and blood stasis, and endogenous phlegm dampness". The liver belongs to wood, is in charge of ascending and dispersing, and likes smoothness and hates depression. Stagnation of liver qi blocks the qi mechanism, leading to disorder of transportation and transformation, unsmooth blood circulation, retention of water and dampness, and endogenous phlegm, stasis and turbidity. Phlegm and stasis accumulate in the liver meridian, and combined with the failure of the liver to disperse and dredge, it is unable to assist the spleen, damaging the transportation and transformation of the spleen and stomach and the ascending and descending of clear and turbid qi. The spleen and stomach belong to earth, the foundation of all things, responsible for transporting water and grains. When the qi mechanism in the middle jiao is unsmooth, the transportation and transformation function declines, and the ascending and descending of clear and turbid qi is damaged. The essence of water and grains and remnants of food cannot reach their destinations and accumulate in the liver. This disease is attributed to qi, and phlegm, dampness, turbidity, and stasis are the main pathological products, accumulating in the liver and causing the disease; the coexistence of excessive pathogens and deficiency of healthy qi belongs to the syndrome of intermingled deficiency and excess.

[0010] When studying MASLD, according to clinical application experience, the present invention flexibly combines herbs and innovatively uses Quzhiqiao, an important herb for regulating qi, as the monarch herb in the formula, leading the function of promoting qi circulation and relieving stagnation. The lotus leaf strengthens the spleen and resolves dampness, enters the liver, spleen, and stomach meridians, and promotes the function of ascending yang and resolving dampness; the cassia seed clears the liver heat, belongs to the liver and large intestine meridians, and promotes the function of purging the bowels and descending turbidity. The two are used as ministerial herbs together. The monarch and ministerial herbs assist each other, ascending the clear qi, descending the turbid qi, and regulating the smooth operation of the qi mechanism in the middle jiao. Gynostemma pentaphyllum, rhodiola rosea, and alisma orientale strengthen the spleen and replenish qi, remove dampness and turbidity, and cooperate with salvia miltiorrhiza and notoginseng to remove stasis without damaging healthy qi, and are used as assistant herbs together to assist the monarch and ministerial herbs in smoothing the transportation and transformation in the middle jiao and clearing food accumulation, stasis, and turbidity. Raw atractylodes macrocephala functions mainly to dry dampness and promote diuresis, and harmonize all the herbs, guarding against the greasy effect of replenishing qi; cinnamon twig warms yang and promotes the transformation of qi, preventing cold from damaging the middle jiao. The two are used as envoy herbs in the formula.

[0011] The present invention also provides a traditional Chinese medicine compound preparation for treating metabolic dysfunction-associated fatty liver disease prepared from the traditional Chinese medicine composition for treating metabolic dysfunction-associated fatty liver disease.

[0012] The dosage forms of the traditional Chinese medicine compound preparation for treating metabolic dysfunction-related fatty liver disease include tablets, capsules, powders, pills, fluid extracts or decoctions, etc. Various pharmaceutically acceptable excipients can be added to various dosage forms. Preferably, a decoction is used.

[0013] Furthermore, when the traditional Chinese medicine compound preparation is a decoction, it is prepared by the following method: Take Aurantii Fructus Immaturus, Folium Nelumbinis, Semen Cassiae, Gynostemma Pentaphyllum, Rhizoma Alismatis, Rhodiola Rosea, Radix Salviae Miltiorrhizae, Radix Notoginseng, and Rhizoma Atractylodis Macrocephalae according to the formula, decoct with water three times. For the first time, add water with a mass 3 times that of the raw medicine amount, bring to a boil over high heat and then decoct over low heat for 30 - 40 minutes. For the second time, add water with a mass 2 times that of the raw medicine amount, bring to a boil over high heat and then decoct over low heat for 30 - 40 minutes. For the third time, add water with the same mass as the raw medicine amount, bring to a boil over high heat and then decoct over low heat for 30 - 40 minutes. Combine the medicinal liquids obtained by filtering after the three decoctions and use them as a decoction for later use.

[0014] The present invention also provides the use of the traditional Chinese medicine composition for treating metabolic dysfunction-related fatty liver disease or the traditional Chinese medicine compound preparation for treating metabolic dysfunction-related fatty liver disease in the preparation of a drug for treating metabolic dysfunction-related fatty liver disease.

[0015] The present invention also provides the use of the traditional Chinese medicine composition for treating metabolic dysfunction-related fatty liver disease or the traditional Chinese medicine compound preparation for treating metabolic dysfunction-related fatty liver disease in the preparation of a drug for repairing liver injury, regulating blood lipid disorders, reducing blood glucose levels, alleviating liver inflammation, reducing liver lipid accumulation, and improving liver fibrosis.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The traditional Chinese medicine composition and the traditional Chinese medicine compound preparation provided by the present invention not only have the effect of improving liver lipid accumulation, inflammation and fibrosis in MASLD, but also have a better clinical effect on improving blood glucose and blood lipids. By improving blood glucose and blood lipid metabolism, slowing down liver fibrosis, repairing liver injury, improving the metabolic level and improving the quality of life of patients, they have the medicinal effects of regulating qi and soothing the liver, strengthening the spleen and removing stasis, resolving phlegm and removing dampness, are inexpensive, and have good commercial value and prospects. Description of the Drawings

[0017] Figure 1 It is a graph showing the effects of the traditional Chinese medicine composition on alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in the serum of mice, where, **** p < 0.0001 vs control group; p < 0.001 vs model group; # p < 0.0001 vs model group..

[0018] Figure 2Results of the effects of the traditional Chinese medicine composition on low-density lipoprotein and high-density lipoprotein in mouse serum. In the figure, **** p < 0.0001 vs control group; # p < 0.05 vs model group; ## p < 0.01 vs model group; p < 0.001 vs model group; # p < 0.0001 vs model group.

[0019] Figure 3 Results of the glucose tolerance test in mice. In the figure, **** p < 0.0001 vs control group; p <0.001 vs model group; # p < 0.0001 vs model group.

[0020] Figure 4 HE staining map of the liver of mice in Example 2.

[0021] Figure 5 Oil Red O staining map of the liver of mice in Example 2.

[0022] Figure 6 Masson and Sirius red staining map of the liver of mice in Example 2.

[0023] Figure 7 Results of the effects of the traditional Chinese medicine composition composed of different drugs on alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in mouse serum. Among them, **** p < 0.0001 vs control group; ## p < 0.01 vs model group; p < 0.001 vs model group; # p < 0.0001 vs model group.

[0024] Figure 8 Results of the effects of the traditional Chinese medicine composition composed of different drugs on low-density lipoprotein and high-density lipoprotein in mouse serum. In the figure, **** p < 0.0001 vs control group; p < 0.001 vs model group; # p <0.0001 vs model group.

[0025] Figure 9 HE staining map of the liver of mice in Example 3.

[0026] Figure 10 Oil red O staining map of the liver of the mouse in Example 3.

[0027] Figure 11 Masson and Sirius red staining maps of the liver of the mouse in Example 3. Detailed implementation manners

[0028] To make the objectives, technical solutions and advantages of the present application clearer and more understandable, the technical solutions of the present invention will be described in detail below in conjunction with embodiments, but the protection scope of the present invention is not limited thereto.

[0029] Example 1 Take 12 parts of Aurantii Fructus Immaturus, 12 parts of Folium Nelumbinis, 18 parts of Cassiae Semen, 12 parts of Gynostemmae Herba, 9 parts of Alismatis Rhizoma, 9 parts of Rhodiolae Crenulatae Radix et Rhizoma, 9 parts of Salviae Miltiorrhizae Radix, 6 parts of Notoginseng Radix et Rhizoma, and 6 parts of Atractylodis Macrocephalae Rhizoma. This formula is a qi-regulating and lipid-lowering formula. Add water with a mass 3 times that of the raw drug amount, bring to a boil over high heat and then simmer for 30 minutes to obtain the first decoction (dissolving small molecule water-soluble components such as iridoid glycosides and flavonoid glycosides). Retain the decoction obtained from the first decoction, add water with a mass 2 times that of the raw drug amount again, bring to a boil over high heat and then simmer for 30 minutes, and filter to obtain the second decoction (releasing bound components such as polysaccharides and alkaloids); add water with a mass equal to that of the raw drug amount again, bring to a boil over high heat and then simmer for 30 minutes. Combine the medicinal liquids obtained from the three decoctions and use them as a decoction for later use.

[0030] Concentrate the prepared decoction for mass spectrometry detection and analysis. The main components are shown in Table 1 below: Table 1 Name Classification Relative Concentration in Compound (μg / g) Relative Percentage (%) Quercetin-3-glucuronide Flavonoid 3913.589886 9.9468% Naringin Flavonoid 3369.767571 8.5646% Neohesperidin Cyclobutane Lignan 3103.246782 7.8872% Jaceosidin Flavonoid 1944.740435 4.9427% Citric Acid Carboxylic Acid and Its Derivatives 1758.19676 4.4686% Salidoside Organic Oxygen Compound 1573.757226 3.9999% Hesperidin Flavonoid 1397.86789 3.5528% Narirutin Flavonoid 1138.997008 2.8949% Kaempferol Flavonoid 953.745361 2.4240% Rutin Flavonoid 722.5559405 1.8364% Table 1 shows the top ten active components in terms of concentration in the qi-regulating and lipid-lowering formula. Among them, naringin, neohesperidin, hesperidin, and rutacridone epoxide are all important active components of the monarch drug Aurantii Fructus Immaturus. The mass spectrometry results further suggest the core position of the monarch drug Aurantii Fructus Immaturus in the qi-regulating and lipid-lowering formula.

[0031] Example 2 Animal experiment 1. Establish a mouse model of MASLD induced by a high-fat diet Feed mice with a high-fat diet for 8 weeks to construct a fatty liver disease model. At this stage, obvious liver lipid deposition, inflammation, and cell damage occur. To promote the occurrence of liver fibrosis, while continuing to feed the high-fat diet, starting from the 8th week, inject CCL4 (0.5 μl / g of mouse body weight) intraperitoneally to induce liver fibrosis. A total of 16 weeks are used to establish a mouse model of MASLD induced by a high-fat diet.

[0032] 2. Intervention experiment From the 8th week, CCl4 was administered simultaneously with drug intervention. Intervention was carried out when fibrosis began to form to evaluate the inhibitory and improvement effects of traditional Chinese medicine on the occurrence and development of fibrosis. The equivalent dose for mice was calculated according to the clinical dosage of the Liqi Tiaozhi Prescription. The clinical equivalent dose for mice was 15.99 g / kg, which was set as the medium dose. The low dose was 1 / 2 of the clinical equivalent dose: 8.00 g / kg. The high dose was 2 times the clinical equivalent dose: 31.98 g / kg. Gavage was performed twice a day, morning and evening, for a total of 8 weeks. And a positive drug resmetirom group for MASLD was set up. From the 8th week, mice were gavaged with 3 g / kg resmetirom. By comparing the pharmacodynamic effects with the positive drug resmetirom, the therapeutic effect of the Liqi Tiaozhi Prescription in improving MASLD was visually demonstrated.

[0033] 3. Result Discussion Automatic biochemical analyzer was used to analyze and detect biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the sera of mice in the normal group, treatment group, and model group. The changes in the relevant end-point indexes of the blank group, model group, and treatment group were compared. SPSS 22.0 statistical software was used to process the data. Unpaired t-test was used to calculate the differences between two groups, and one-way ANOVA was used to calculate the differences and statistical significance among multiple groups. Measurement data were expressed as mean ± standard deviation (x±sd). The obtained results were as Figure 1-2 shown.

[0034] The glucose tolerance test (GTT) reflects the body's ability to regulate blood glucose concentration. The experimental method is as follows: At 5 pm the day before the experiment, the mice were transferred to clean cages and fasted for 16 h. During fasting, the mice drank water normally. The next day, the mice were taken out of the cages and gently placed on the iron grid. The end of the mouse's tail was cut off about 1-2 mm with scissors, and the tail was squeezed to obtain the second drop of blood. The fasting blood glucose was measured with a blood glucose meter as the blood glucose value at 0 min. Subsequently, 2 g / kg glucose solution was gavaged. The blood glucose values of the mice were measured at 30 min, 60 min, 90 min, and 120 min respectively. The obtained results were as Figure 3 shown.

[0035] The liver tissues of the mice were paraffin-embedded and stained with HE, Oil Red O, Masson, and Sirius red. The photos were as Figure 4-6 shown, and the magnification was X 200 for all.

[0036] Figure 1The results showed that: obvious liver damage occurred in the mice of the model group, manifested as significantly increased levels of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase compared with those of the control group mice (p < 0.05). After treatment with the Liqi Tiaozhi Formula, the levels of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the mice were improved, and the drug efficacy was positively correlated with the dose. The therapeutic effect of Resmetirom on liver injury in mice was also extremely excellent, similar to that of the high-dose Liqi Tiaozhi Formula. Therefore, Figure 1 It is indicated that this formula can improve liver injury in MASLD mice induced by a high-fat diet, and the drug efficacy of the high dose is similar to that of Resmetirom.

[0037] Figure 2 The results showed that: the Liqi Tiaozhi Formula had a good drug efficacy in improving the blood lipid of mice. After drug treatment, the level of high-density lipoprotein in the mice was significantly improved (p < 0.05), while the low-density lipoprotein was significantly decreased. Therefore, Figure 2 It is indicated that this formula can improve blood lipid disorders in MASLD mice induced by a high-fat diet.

[0038] Figure 3 It was shown that: the fasting blood glucose of the mice in the model group was higher than 10 mmol / l, reaching the threshold for diagnosing type 2 diabetes; after glucose administration, the blood glucose of the mice in the model group increased rapidly and decreased slowly, suggesting impaired islet function. The fasting blood glucose of the mice in the Liqi Tiaozhi Formula treatment group was improved. At the same time, the rising amplitude of blood glucose was significantly lower than that of the mice in the model group and decreased rapidly over time. Comparison with the Resmetirom group showed that the high-dose Liqi Tiaozhi Formula had a better effect on improving blood glucose in mice, highlighting the unique advantage of the Liqi Tiaozhi Formula in improving blood glucose. Therefore, Figure 3 It is indicated that this formula can regulate the blood glucose level of MASLD mice induced by a high-fat diet.

[0039] Figure 4 It was shown that: obvious liver damage and liver inflammation occurred in the mice of the model group, manifested as hepatocyte edema and ballooning degeneration in the liver, and infiltration of inflammatory cells and focal necrosis foci in the portal area; in contrast, the liver tissue structure of the mice in the Liqi Tiaozhi Formula and Resmetirom groups was relatively intact, the hepatic cords were arranged neatly in a radial pattern, the hepatocyte structure was regular, the cell nuclei were clear, and no obvious abnormal changes such as hepatocyte edema or vacuoles were found. The area of ballooning degeneration decreased, and the cell morphology gradually returned to normal; the density of inflammatory cells decreased, and the infiltration area decreased. Therefore, Figure 4 It is indicated that this formula has the effect of improving liver inflammation and injury, but the drug efficacy is slightly inferior to that of Resmetirom.

[0040] Figure 5It was shown that almost no red lipid droplets could be seen in the liver tissues of the mice in the control group, the hepatocytes were arranged neatly, and there was no obvious lipid accumulation. In the hepatocytes of the mice in the model group, there were a large number of large lipid droplets, which even squeezed the cell nucleus, resulting in deformation of the hepatocyte structure. The Liqi Tiaozhi Formula improved the lipid deposition in the livers of mice in a dose-dependent manner. In the mice treated with the high-dose Liqi Tiaozhi Formula, only a small number of small lipid droplets were scattered in the hepatocytes and were sparsely distributed. Therefore, Figure 5 it was shown that this formula had the effect of reducing lipid accumulation in the liver.

[0041] Figure 6 It was shown that obvious collagen fiber deposition appeared in the livers of the mice in the model group, which was mostly concentrated in the portal area and formed a small amount of fibrous septa, but did not completely separate the hepatic lobules, showing moderate fibrosis. The hepatic fibrosis in the mice in the treatment group with the Liqi Tiaozhi Formula was significantly improved, and collagen fibers were only present in the portal area and around blood vessels, and there was no fibrosis in the hepatic lobules. Therefore, Figure 6 it was shown that this formula had the effect of improving liver fibrosis in MASLD.

[0042] Example 3 Animal experiment 1. Establish a mouse model of MASLD induced by a high-fat diet Mice were fed a high-fat diet for 8 weeks to construct a fatty liver disease model. At this stage, obvious lipid deposition, inflammation and cell damage in the liver appeared. To promote the occurrence of liver fibrosis, while continuing to feed the high-fat diet, CCl4 (0.5 μl / g mouse body weight) was intraperitoneally injected from the 8th week to induce liver fibrosis. In total, for 16 weeks, a mouse model of MASLD induced by a high-fat diet was established.

[0043] 2. Intervention experiment From the 8th week, while CCl4 was given, drug intervention was also carried out. The Liqi Tiaozhi Formula of Example 1 was selected, and the dose was the clinical equivalent dose for mice, 15.99 g / kg. At the same time, a group intervened with only the monarch drug Quzhike and a group intervened with the Liqi Tiaozhi Formula without Quzhike (that is, the formula was 12 parts of lotus leaf, 18 parts of cassia seed, 12 parts of gynostemma pentaphyllum, 9 parts of alisma orientale, 9 parts of rhodiola rosea, 9 parts of salvia miltiorrhiza, 6 parts of notoginseng, 6 parts of raw atractylodes macrocephala, prepared according to the method of Example 1) were added, and the doses were both 15.99 g / kg. It was administered by gavage twice a day, morning and evening, for a total of 8 weeks of intervention. Through the comparison of the drug effects, the importance of Quzhike in the composition of the Liqi Tiaozhi Formula and the curative effect of the constructed formula (not only using Quzhike alone) were intuitively demonstrated.

[0044] 3. Result discussion The automatic biochemical analyzer was used to analyze and detect biochemical indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the sera of mice in the normal group, treatment group, and model group. The changes in the relevant endpoint indicators of the blank group, model group, and treatment group were compared. The SPSS 22.0 statistical software was used to process the data. The unpaired t-test was used to calculate the differences between the two groups, and one-way ANOVA was used to calculate the differences and statistical significance among multiple groups. Measurement data were expressed as mean ± standard deviation (x±sd). The results were as Figure 7-8 shown.

[0045] The liver tissues of the mice were paraffin-embedded and stained with HE, Oil Red O, Masson, and Sirius red. The photos were as Figure 9-11 shown, and the magnification was X200 for all.

[0046] Figure 7 The results showed that obvious liver damage occurred in the mice in the model group, manifested as a significant increase in serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase compared with the control group mice (p < 0.05). After treatment with the Liqi Tiaozhi Prescription, the levels of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the mice were improved. The single use of Quzhique and the Liqi Tiaozhi Prescription without Quzhique also had a certain effect on improving liver injury in mice, but the drug effects were inferior to those of the Liqi Tiaozhi Prescription. Therefore, Figure 7 it was shown that the Liqi Tiaozhi Prescription could improve liver injury in MASLD mice induced by a high-fat diet, and its drug effect was better than that of single use of Quzhique or the prescription without Quzhique.

[0047] Figure 8 The results showed that the Liqi Tiaozhi Prescription had a good drug effect on improving the blood lipids of mice. After drug treatment, the high-density lipoprotein level in the mice was significantly improved (p < 0.05), while the low-density lipoprotein was significantly decreased (p < 0.05). The curative effects of Quzhique and the Liqi Tiaozhi Prescription without Quzhique were inferior to those of the Liqi Tiaozhi Prescription. Figure 8 It was shown that the prescription of this formula was reasonable. Quzhique, as the monarch drug, played a great role and was indispensable. At the same time, if only Quzhique was used alone without the assistance of other drugs, the drug effect of improving blood lipid disorders in MASLD mice induced by a high-fat diet could not be achieved as well as that of the complete formula of the Liqi Tiaozhi Prescription.

[0048] Figure 9It was shown that obvious liver injury and liver inflammation occurred in the mice of the model group, manifested as hepatocyte swelling and ballooning degeneration in the liver, and infiltration of inflammatory cells and focal necrosis in the portal area; in contrast, the liver tissue structures of the mice in the Qizhi Tiaozhi Formula group, the Aurantii Fructus Immaturus group, and the Qizhi Tiaozhi Formula without Aurantii Fructus Immaturus group were relatively intact, the ballooning degeneration area decreased, and the cell morphology gradually returned to normal; the infiltration of inflammatory cells decreased. Compared with the Qizhi Tiaozhi Formula group, the improvement of liver inflammation in the Aurantii Fructus Immaturus group and the Qizhi Tiaozhi Formula without Aurantii Fructus Immaturus group was significantly insufficient. Therefore, Figure 9 it was indicated that this formula had the effect of improving liver inflammation and injury, and the efficacy of this formula needed to be achieved by the combination of various traditional Chinese medicines in the formula. Using Aurantii Fructus Immaturus alone or removing Aurantii Fructus Immaturus could not achieve the expected efficacy.

[0049] Figure 10 It was shown that a large amount of lipid droplets accumulated in the hepatocytes of the mice in the model group. Qizhi Tiaozhi Formula, Aurantii Fructus Immaturus, and Qizhi Tiaozhi Formula without Aurantii Fructus Immaturus could all significantly improve liver lipid deposition in mice. Among them, Qizhi Tiaozhi Formula had the best effect. Therefore, Figure 10 this formula had the effect of reducing liver lipid deposition, and the efficacy of this formula needed to be achieved by the combination of various traditional Chinese medicines in the formula. Using Aurantii Fructus Immaturus alone or removing Aurantii Fructus Immaturus could not achieve the efficacy of the complete formula.

[0050] Figure 11 It was shown that obvious collagen fiber deposition occurred in the liver of the mice in the model group. Liver fibrosis in the mice was significantly improved after treatment with Qizhi Tiaozhi Formula. Aurantii Fructus Immaturus and Qizhi Tiaozhi Formula without Aurantii Fructus Immaturus could also significantly improve liver fibrosis in mice, but the efficacy was far less than that of Qizhi Tiaozhi Formula. Therefore, Figure 11 it was indicated that this formula had the effect of improving liver fibrosis, and the efficacy of this formula needed to be achieved by the combination of various traditional Chinese medicines in the formula. Using Aurantii Fructus Immaturus alone or removing Aurantii Fructus Immaturus could not achieve the efficacy of the complete formula.

Claims

1. A Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction, characterized in that The Chinese medicine composition comprises the following raw materials: Citrus aurantium, lotus leaf, cassia seed, Gynostemma pentaphyllum, Alisma orientalis, Rhodiola rosea, Salvia miltiorrhiza, Panax notoginseng, Atractylodes macrocephala.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 10-15 parts of Quzhi Fructus, 10-15 parts of lotus leaves, 15-20 parts of cassia seeds, 10-15 parts of gynostemma pentaphyllum, 6-12 parts of oriental water chestnuts, 6-12 parts of rhodiola rosea, 6-12 parts of salvia miltiorrhiza, 4-8 parts of Panax notoginseng, and 4-8 parts of raw atractylodes macrocephala.

3. The Chinese medicine composition as claimed in claim 2, characterized in that The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 10-12 parts of Quzhi Fructus, 10-12 parts of lotus leaves, 16-18 parts of cassia seeds, 10-12 parts of gynostemma pentaphyllum, 8-9 parts of oriental water plantain, 8-9 parts of rhodiola rosea, 8-9 parts of salvia miltiorrhiza, 5-6 parts of Panax notoginseng, and 5-6 parts of raw Atractylodes macrocephala.

4. The Chinese medicine composition as claimed in claim 3, characterized in that The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 12 parts of Quzhi Fructus, 12 parts of lotus leaves, 18 parts of cassia seeds, 12 parts of gynostemma pentaphyllum, 9 parts of oriental water chestnuts, 9 parts of rhodiola rosea, 9 parts of salvia miltiorrhiza, 6 parts of Panax notoginseng, and 6 parts of raw atractylodes.

5. A Chinese medicine compound preparation for treating fatty liver disease associated with metabolic dysfunction prepared by the Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction according to any one of claims 1 to 4.

6. The Chinese medicinal compound preparation for treating fatty liver disease associated with metabolic dysfunction according to claim 5, characterized in that The dosage form of the Chinese medicinal compound preparation for treating fatty liver disease associated with metabolic dysfunction includes tablets, capsules, powders, pills, fluid extracts or decoctions.

7. Use of the Chinese medicine composition for treating metabolic dysfunction-related fatty liver disease according to any one of claims 1 to 4 or the Chinese medicine compound preparation for treating metabolic dysfunction-related fatty liver disease according to claim 5 or 6 in the preparation of a medicament for treating metabolic dysfunction-related fatty liver disease.

8. Use of the Chinese medicine composition for treating fatty liver disease associated with metabolic dysfunction as described in any one of claims 1 to 4 or the Chinese medicine compound preparation for treating fatty liver disease associated with metabolic dysfunction as described in claim 5 or 6 in the preparation of drugs for repairing liver damage, regulating dyslipidemia, lowering blood sugar levels, alleviating liver inflammation, reducing liver lipid accumulation, and improving liver fibrosis.

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