Application of a kind of compound jujube vinegar of codonopsis lanceolata in the preparation of drugs for preventing and treating acute liver injury

Abstract

The application provides application of a Codonopsis lanceolata composite fruit vinegar in preparation of a drug for preventing and treating acute liver injury, and belongs to the technical field of medicines.The Codonopsis lanceolata composite fruit vinegar is prepared from Codonopsis lanceolata as raw material and a composite fermentation fruit vinegar prepared from Pueraria lobata and Hovenia dulcis as research object, an acute alcoholic liver injury model of mice is established, the activities of ALT and AST in serum of the mice and the contents of TC, TG, LDL-C and HDL-C in serum of the mice and the contents of SOD, MDA and GSH in liver tissue of the mice are determined, and pathological sections of the livers of the mice are used as evaluation indexes, and it is found that the Codonopsis lanceolata composite fruit vinegar has a remarkable prevention and treatment effect on acute alcoholic liver injury.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to the application of a compound fruit vinegar of Codonopsis pilosula in the preparation of drugs for the prevention and treatment of acute liver injury. Background Technology

[0002] Acute alcoholic liver damage refers to a condition caused by excessive alcohol consumption within a short period, leading to acute liver injury. The main process involves alcohol metabolism via the liver, skin, and respiratory system, with the liver being the most crucial, metabolizing over 90% of alcohol. Under normal conditions, alcohol is primarily converted to acetaldehyde by alcohol dehydrogenases. Acetaldehyde then undergoes oxidation by dehydrogenases, converting back to acetic acid. Acetic acid enters the tricarboxylic acid cycle, ultimately producing CO2 and H2O, which is excreted from the body. However, with excessive alcohol consumption, the dehydrogenase system alone cannot complete the metabolism of all alcohol. The body also needs the assistance of mitochondrial enzymes such as alcohol oxidase and catalase to oxidize the unmetabolized alcohol back to acetaldehyde. This acetaldehyde is then converted to acetic acid by ALDH in the tricarboxylic acid cycle. When the amount of alcohol entering the body exceeds its metabolic capacity, the unmetabolized alcohol accumulates. Excessive alcohol accumulation damages liver cells and organelles, leading to the formation of highly toxic and reactive acetaldehyde. In addition, alcohol produces acetaldehyde compounds that are toxic to body tissues and cells, leading to the inactivation of proteases in liver cells, impaired DNA repair, metabolic disorders, and a series of problems such as inducing liver fibrosis and cirrhosis. Furthermore, ethanol metabolism generates reactive oxygen species and reactive nitrogen species. Alcohol-mediated oxidative stress can inhibit fatty acid β-oxidation-related enzymes and impair electron transfer in the mitochondrial respiratory chain, resulting in the breakdown of triglycerides in liver cells. The accumulation of large amounts of lipids causes lipid peroxidation, further damaging liver cells. The oxidation and antioxidant systems in a normal human body maintain a dynamic balance. However, excessive alcohol severely affects the production and clearance of reactive molecules such as oxygen and nitrogen, leading to oxidative stress, immune disorders, and cytokine imbalances, further damaging liver function. In recent years, the incidence of acute alcoholic liver injury in my country has been rising annually, posing a significant threat to the health of the Chinese population. Therefore, it is necessary to further explore the protective effects of traditional Chinese medicine against acute alcoholic liver injury and discover more drugs with interventional and therapeutic effects on acute alcoholic liver injury, which is of great significance for the clinical treatment of acute alcoholic liver injury.

[0003] Codonopsis lanceolata, a perennial herb belonging to the Campanulaceae family and the Codonopsis genus, is also known as Yangru, Siyeshen, and Shandigua. It is a valuable traditional Chinese medicine and edible plant in the Changbai Mountain region, primarily growing in humid forests. Codonopsis lanceolata contains abundant active ingredients with antioxidant, anti-inflammatory, anti-cancer, lipid-lowering, immune-regulating, and liver-protective effects. Studies have shown that Codonopsis lanceolata extract can prevent lipid peroxidation and inflammation in patients with prehypertension. Currently, the main products developed using Codonopsis lanceolata include low-salt foods, Codonopsis lanceolata chips, and fermented beverages. Fermented Codonopsis lanceolata can enhance its ability to scavenge oxygen free radicals. In recent years, with the rapid development of biotechnology, in-depth research has been conducted on various chemical substances and physiological functions of Codonopsis lanceolata, leading to the discovery of many new active ingredients and pharmacological effects. Kudzu root (Pueraria lobata) is the dried root of a wild legume and a traditional Chinese medicinal herb used in both food and medicine. It is known for its effects in treating wounds, relieving fever and promoting body fluid production, and invigorating yang and stopping diarrhea. It is recorded in the *Shennong Bencao Jing*, *Bencao Shiyi*, and the *Chinese Pharmacopoeia*. Kudzu root contains many pharmacologically active components, such as isoflavones, saponins, and polysaccharides. Puerarin, a pharmacologically active isoflavone, possesses antioxidant, anticancer, anti-inflammatory, neuroprotective, alcohol-controlling, cardioprotective, and insulin-resistance-reducing properties. Furthermore, kudzu root can be used as a common hangover remedy; the isoflavones it contains are the main active ingredients, effectively relieving hangovers and preventing intoxication, and have a good liver-protective effect. Fermented kudzu root may also enhance its medicinal value; Zhao et al. found that fermented kudzu root liquid promotes the growth of antioxidant genes. The rapid development of kudzu has made people aware of its importance, thus promoting its development and utilization. It has been widely studied and applied in modern soil and plant research, further broadening its development in medicine and food. Hovenia acerba Lindl., belonging to the Rhamnaceae family and the Hovenia genus, is also known as jujube. Studies have shown that Hovenia acerba contains flavonoids, alkaloids, saponins, glycosides, and other effective substances, possessing hepatoprotective, anti-inflammatory, anti-cancer, and anti-lipid peroxidation effects.

[0004] Fruit vinegar is an acidic beverage and condiment. Its rich nutrients and unique flavor give it the dual benefits of both fruit and vinegar. Fruit vinegar contains bioactive components such as flavonoids and polyphenols, and possesses significant antioxidant capabilities. In addition to these, fruits and fruit processing byproducts also contain abundant polyphenols, flavonoids, anthocyanins, and vitamins, among other bioactive substances. Furthermore, the efficacy of vinegar stems from its inherent bioactive components, including acetic acid, catechins, gallic acid, chlorogenic acid, caffeic acid, and coumaric acid, which possess antibacterial, antioxidant, antihypertensive, anti-obesity, and cholesterol-lowering effects.

[0005] However, there are currently no reports on the application of combining traditional Chinese medicine compatibility theory with fruit vinegar preparation in the treatment of acute alcoholic liver injury. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides an application of Codonopsis pilosula compound fruit vinegar in the preparation of drugs for the prevention and treatment of acute liver injury. This invention uses Codonopsis pilosula as the raw material, along with Pueraria lobata and Hovenia dulcis, to create a compound fermented fruit vinegar. An acute alcoholic liver injury model was established in mice. The activities of ALT and AST, and the contents of TC, TG, LDL-C, and HDL-C in mouse serum, as well as the contents of SOD, MDA, and GSH in mouse liver tissue, were measured. Mouse liver pathological sections were used as evaluation indicators. The results showed that the Codonopsis pilosula compound fruit vinegar has a significant preventive and therapeutic effect on acute alcoholic liver injury.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] This invention provides an application of Codonopsis pilosula compound fruit vinegar in the preparation of drugs for the prevention and treatment of acute liver injury. The Codonopsis pilosula compound fruit vinegar is first prepared by a compound liquid consisting of 20-30% by weight Codonopsis pilosula extract, 15-25% by weight Pueraria lobata extract, 5-15% by weight Hovenia dulcis extract, and 40-50% by weight apple extract. Then, the mixture is fermented with alcohol and acetic acid to obtain a fermentation liquid, and finally clarified with pectinase solvent to obtain the final product.

[0009] Furthermore, the Codonopsis pilosula extract is prepared by soaking Codonopsis pilosula slices in 5-7 times their weight of water for 5-7 hours, then juicing, pulping, and filtering; the Pueraria lobata extract is prepared by adding 14-16 times their weight of water to Pueraria lobata, water bathing at 75-85℃ for 25-35 minutes, cooling to room temperature, juicing, pulping, and filtering at a weight ratio of raw material:water = 1:(14-16); the Hovenia dulcis extract is prepared by adding 9-11 times their weight of water to crushed Hovenia dulcis, water bathing at 75-85℃ for 25-35 minutes, cooling to room temperature, juicing, pulping, and filtering at a weight ratio of raw material:water = 1:(9-11); and the apple extract is prepared by peeling apples, adding 4-6 times their weight of water, and juicing.

[0010] Furthermore, the mixed mass percentages of the Codonopsis pilosula extract, the Pueraria lobata extract, the Hovenia dulcis extract, and the apple extract are 25%, 20%, 10%, and 45%, respectively.

[0011] The apples used are fresh weight, which has a high moisture content, while the Codonopsis pilosula, Hovenia dulcis, and Pueraria lobata are dry weight, which have a low moisture content. Therefore, more apples are added in the ingredient ratio.

[0012] Furthermore, the alcoholic fermentation process is as follows: yeast is added to a sucrose solution with a mass percentage of 4-6% for activation. After activation, it is mixed evenly with the compound liquid and fermented for 6-8 days. The yeast inoculation amount is 0.6-1.0%. The fermentation temperature is 28-32℃. The apparent sugar content is 16-20%. The initial pH value is 2.5-3.5.

[0013] Furthermore, the yeast inoculation amount is 1.0%; the fermentation temperature is 30°C; the apparent sugar content is 20%; and the initial pH value is 3.0.

[0014] Furthermore, the acetic acid fermentation process is as follows: after the alcoholic fermentation is completed, acetic acid bacteria are poured into the fermentation broth and cultured in a constant temperature shaking incubator for 6-8 days; wherein the inoculation amount of acetic acid bacteria is 0.6-1.2%; the fermentation temperature is 28-32℃; the rotation speed of the constant temperature shaking incubator is 110-130 r / min; and the initial pH value is 4.5-5.5.

[0015] Furthermore, the inoculum amount of acetic acid bacteria is 0.9%; the fermentation temperature is 30℃; the rotation speed of the constant temperature shaking incubator is 120r / min; and the initial pH value is 4.5.

[0016] Furthermore, the pectinase solvent is prepared by mixing pectinase and water at a weight ratio of 1:(8-12); the method of using the pectinase solvent is as follows: add 0.8-1.2 mL of the pectinase solvent to every 4.5-5.5 L of the fermentation broth.

[0017] Furthermore, the pectinase solvent is prepared by mixing pectinase and water at a weight ratio of 1:10; the method of using the pectinase solvent is as follows: add 1 mL of the pectinase solvent to every 5 L of the fermentation broth.

[0018] Compared with the prior art, the present invention has the following technical effects:

[0019] The experiments of this invention revealed that the liver index of mice in the blank control group was significantly lower than that in the model group (P<0.01), while the liver index in the Codonopsis pilosula compound fruit vinegar intervention group was higher than that in the blank control group. Compared with the blank control group, the serum ALT and AST activities, as well as TG, TC, LDL-C, and liver tissue MDA content in the model group mice were significantly increased (P<0.01), while the HDL-C, GSH, and SOD contents were significantly decreased (P<0.01). In addition, when performing liver tissue sections, disordered liver tissue structure was observed in the model group. Compared with the model group, the intervention group of Codonopsis pilosula compound fruit vinegar showed significantly decreased serum ALT and AST activities, TG, TC, and LDL-C levels (P<0.05 or P<0.01), and increased HDL-C levels (P<0.05 or P<0.01); decreased MDA levels in liver tissue (P<0.01), and significantly increased GSH and SOD levels (P<0.05 or P<0.01); HE staining of liver tissue showed a reduction in lipid droplets in mouse liver. This indicates that the Codonopsis pilosula compound fruit vinegar of this invention has a good preventive and protective effect against acute alcohol-induced liver injury in mice. Attached Figure Description

[0020] Figure 1 This is a graph showing the effects of each treatment group on liver function in mice in Example 1 of the present invention;

[0021] Figure 2 This is a graph showing the effect of each treatment group on the serum TC content of mice in Example 1 of the present invention;

[0022] Figure 3 This is a graph showing the effect of each treatment group on the serum TG level of mice in Example 1 of the present invention;

[0023] Figure 4 This is a graph showing the effect of each treatment group on the serum HDL-C content of mice in Example 1 of the present invention;

[0024] Figure 5 This is a graph showing the effect of each treatment group on the serum LDL-C content of mice in Example 1 of the present invention;

[0025] Figure 6 This is a graph showing the effect of each treatment group on the MDA content in mouse liver tissue in Example 1 of the present invention;

[0026] Figure 7 This is a graph showing the effect of each treatment group on the SOD content in mouse liver in Example 1 of the present invention;

[0027] Figure 8 This is a graph showing the effect of each treatment group on the GSH content in mouse liver in Example 1 of the present invention;

[0028] Figure 9This is a diagram showing the effects of each treatment group on mouse liver tissue pathological sections in Example 1 of the present invention. Detailed Implementation

[0029] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the invention. Any modifications or substitutions made to the methods, steps, conditions, instruments, or reagents of the present invention without departing from the spirit and essence of the invention are within the scope of the invention.

[0030] The technical solution of the present invention will be further described in detail below with reference to the embodiments.

[0031] Example 1

[0032] 1. The main experimental supplies are listed in Table 1, the main reagents are listed in Table 2, and the main instruments are listed in Table 3.

[0033] Table 1 Main Experimental Supplies

[0034]

[0035]

[0036] Table 2 Main Reagents

[0037]

[0038] Table 3 Main Instruments

[0039]

[0040]

[0041] 2 Experimental Methods

[0042] Codonopsis pilosula, Hovenia dulcis, and Pueraria lobata were processed separately and mixed with apple juice. A liquid fermentation method was used. In the first stage, Saccharomyces cerevisiae was used to ferment the above raw materials into a Codonopsis pilosula compound fruit wine. In the second stage, Acetic Acid Bacillus was used to ferment the Codonopsis pilosula compound fruit wine into a Codonopsis pilosula compound fruit vinegar. The alcoholic fermentation conditions for the first stage were: temperature 30℃, apparent sugar content 20%, Saccharomyces cerevisiae inoculum 1.0%, initial pH 3.0, ultimately yielding a Codonopsis pilosula compound fruit wine with an alcohol content of 19.5%. The acetic acid fermentation conditions for the second stage were: pH 4.5, Acetic Acid Bacillus inoculum 0.9%, fermentation temperature 32℃, and fermentation speed 120 r / min. The final product was a Codonopsis pilosula compound fruit vinegar with an acidity of 2.15 g / 100 mL.

[0043] Clarification: Prepare pectinase solvent (pectinase:water = 1:10), add 1 mL of solvent to 5 L of fermentation broth.

[0044] 3. Animal grouping and model establishment

[0045] Forty experimental mice were randomly divided into five groups of eight each: 1. Blank control group (CON); 2. Model group (EtOH); 3. Low-dose group of Codonopsis pilosula compound fruit vinegar (CFV-L 0.15 g / mL); 4. Medium-dose group of Codonopsis pilosula compound fruit vinegar (CFV-M 0.30 g / mL); 5. High-dose group of Codonopsis pilosula compound fruit vinegar (CFV-H 0.45 g / mL). The Codonopsis pilosula compound fruit vinegar groups were administered the drug via gavage at a dose of 0.1 mL / 10 g, while the blank control group and model group were administered the same amount of distilled water. Normal drinking water and feed were provided throughout the experiment. Codonopsis pilosula compound fruit vinegar was administered continuously for 7 days. Twelve hours after the last gavage, except for the blank control group, the other four groups were administered 50% alcohol via gavage at a dose of 0.1 mL / 10 g. Food and water were restricted. Blood and liver samples were collected 12 hours later.

[0046] 3.1 Liver index measurement

[0047] The animal liver was rinsed in physiological saline at 4°C, and the dried liver weight was measured after absorbing the water.

[0048] Liver index (%) = Liver weight (g) / Mouse body weight (g) × 100%.

[0049] 3.2 Liver tissue preparation

[0050] Blood was collected from mouse eyeballs and centrifuged at 4°C to prepare serum (3000 rpm, 20 min).

[0051] The left lobe of the mouse liver was placed in a tissue staining and fixation box and soaked in 4% paraformaldehyde for at least 72 hours. The remaining liver tissue was aliquoted into cryovials and stored at -80°C.

[0052] 3.3 Hematoxylin and eosin stained sections

[0053] Mouse liver tissue was fixed in paraffin, sectioned, dewaxed, stained, dehydrated, and finally mounted with neutral resin for microscopic observation.

[0054] 3.4 Determination of Biochemical Indicators

[0055] The levels of SOD, GSH, and MDA in liver tissue, as well as the activities of ALT and AST, and the levels of TG, TC, LDL-C, and HDL-C in serum were determined according to the kit instructions.

[0056] 4. Data Analysis

[0057] All data are expressed as mean ± standard deviation and statistical analysis was performed using Prism 7.0. One-way ANOVA and Newman-Keuls multiple comparison analysis were used for statistical analysis (P < 0.05 was considered statistically significant).

[0058] 5 Results and Analysis

[0059] 5.1 Effects of Codonopsis pilosula compound fruit vinegar on liver index in mice

[0060] The effects of each treatment group on the liver index in mice are shown in Table 4.

[0061] Table 4 Liver index of five groups of mice

[0062]

[0063] Note: * P < 0.05 versus CON; ** P < 0.01 versus CON; # P < 0.05 versus EtOH; ## P < 0.01 versus EtOH.

[0064] Liver index is a crucial clinical indicator, commonly used to reflect the physiological and pathological condition of the liver. After ethanol enters the liver, it is metabolized into toxic substances, leading to fat accumulation and inducing hepatocytes to secrete large amounts of inflammatory mediators. Therefore, early-stage alcoholic liver disease presents with obvious fatty liver and inflammatory symptoms, causing liver edema and enlargement. Table 4 shows that compared with the blank control group, the liver index of mice in the model group and each dose group of Codonopsis pilosula compound fruit vinegar was increased. The liver index in the model group increased by 33.92%, a significant difference (P<0.01). Compared with the model group, the liver index in the medium and high dose groups of Codonopsis pilosula compound fruit vinegar decreased by 17.96% and 17.77%, respectively, with significant differences (P<0.01, P<0.05), while the liver index in the low dose group decreased by 7.45%, with no significant difference (P>0.05). These results indicate that alcohol causes fat accumulation in liver tissue, leading to liver enlargement in mice. The compound fruit vinegar of Codonopsis pilosula and Codonopsis pilosula in each intervention group could effectively alleviate alcoholic fatty liver, inhibit liver lesions, and significantly change the effect of alcohol on liver weight in mice.

[0065] 5.2 Effects of Codonopsis pilosula compound fruit vinegar on liver function in mice

[0066] Serum ALT and AST activities can reflect the state of liver function and indicate the degree of liver dysfunction. To observe the effects of Codonopsis pilosula compound fruit vinegar on liver function in mice, we measured ALT and AST activities. The results are as follows: Figure 1 As shown.

[0067] The results showed that compared with the blank control group, the model group had significantly higher ALT and AST levels, with ALT increasing by 125.65% and AST increasing by 147.79% (P<0.01), indicating that alcohol caused liver damage in mice. The serum ALT and AST levels in the low, medium, and high dose groups of the Codonopsis pilosula compound fruit vinegar were all lower than those in the model group, with ALT levels decreasing by 35.42%, 40.17%, and 46.03%, respectively, and AST levels decreasing by 31.26%, 46.64%, and 51.65%, respectively. The ALT and AST levels in the low, medium, and high dose groups were significantly different from those in the model group (P<0.01), indicating that the Codonopsis pilosula compound fruit vinegar alleviated alcohol-induced liver damage in mice and had a good protective effect.

[0068] 5.3 Effects of Codonopsis pilosula compound fruit vinegar on serum lipid metabolism in mice

[0069] Blood lipids refer to the total amount of neutral fats and lipids in blood plasma. A major complication of alcoholic liver injury is abnormal lipid metabolism. Monitoring changes in serum TC, TG, LDL-C, and HDL-C is one of the standards for diagnosing abnormalities in lipid synthesis and metabolism pathways in the body. The detection results of TC, TG, LDL-C, and HDL-C in each treatment group are as follows: Figures 2-5 As shown.

[0070] Figure 2 The results showed that the TC content in the model group increased by 34.27% compared with the blank control group, which was statistically significant (P<0.01). Compared with the model group, the TC content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar decreased by 4.75%, 11.50%, and 22.00%, respectively. The medium and high dose groups of Codonopsis pilosula compound fruit vinegar showed significant differences compared with the model group (P<0.05, P<0.01). The TC content in the low and medium dose groups of Codonopsis pilosula compound fruit vinegar was significantly different from that in the blank control group (P>0.01). The TC content in the high dose group of Codonopsis pilosula compound fruit vinegar was higher than that in the blank control group, but the difference was not statistically significant (P>0.05).

[0071] Figure 3 The results showed that the TG content in the model group increased by 54.49% compared with the blank control group, with a significant difference (P<0.01). Compared with the model group, the TG content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar all decreased, by 10.59%, 17.94%, and 29.05%, respectively, all with significant differences (P<0.05, P<0.01, P<0.01). The TG content in the low-dose and medium-dose groups of Codonopsis pilosula compound fruit vinegar was significantly higher than that in the blank control group (P<0.01), while the TG level in the high-dose group of compound fruit vinegar also increased, but the difference was not significant (P>0.05).

[0072] Figure 4 The results showed that compared with the blank control group, the HDL-C content in the model group mice (0.294 mmol / L) decreased by 32.27%, with a statistically significant difference (P<0.01). Compared with the model group, the HDL-C content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar all showed an increasing trend, increasing by 29.46%, 52.74%, and 23.11%, respectively. There was no significant difference in the low dose group (P>0.05), while the medium and high dose groups showed significant differences (P<0.01, P<0.05). Compared with the blank control group, there was no significant difference in HDL-C levels between the low and medium dose groups of Codonopsis pilosula compound fruit vinegar (P>0.05). The HDL-C level in the high dose group was significantly different from that in the blank control group (P<0.05).

[0073] Figure 5 The results showed that, compared with the blank control group, the serum LDL-C level in the model group mice (0.749 mmol / L) increased by 45.09%, which was statistically significant (P<0.01). Compared with the model group, the LDL-C content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar all showed a decreasing trend, decreasing by 28.42%, 24.67%, and 25.82%, respectively, all with statistically significant differences (P<0.01). There were no statistically significant differences in LDL-C content (0.536 mmol / L, 0.564 mmol / L, and 0.555 mmol / L) between the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar and the blank control group (P>0.05).

[0074] 5.4 Effects of Codonopsis pilosula compound fruit vinegar on the antioxidant capacity of mouse liver tissue

[0075] During alcohol metabolism in the liver, a large number of free radicals (such as reactive oxygen species) are produced. Excessive ROS can induce the formation of lipid peroxidation product MDA, reducing antioxidant levels and causing an imbalance in redox balance. SOD and GSH are important substances for maintaining the body's oxidative balance, but alcohol intake increases reactive oxygen species levels, affecting antioxidant enzyme levels and thus causing liver damage. The detection results of MDA, SOD, and GSH in each treatment group are as follows: Figures 6-8 As shown.

[0076] Figure 6The results showed that the MDA level in the liver tissue of the model group mice was 73.83% higher than that in the blank control group, with a significant difference (P<0.01). Compared with the model group, the MDA content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar all showed a decreasing trend, decreasing by 43.41%, 52.14%, and 28.78%, respectively, with significant differences (P<0.01). The MDA content in the low and medium dose groups of Codonopsis pilosula compound fruit vinegar (1.871 nmol / mgprot, 1.583 nmol / mgprot) was not significantly different from that in the blank control group (P>0.05), while the MDA content in the high dose group (2.355 nmol / mgprot) was 23.80% higher than that in the blank control group, with a significant difference (P<0.01).

[0077] Figure 7 The results showed that, compared with the blank control group, the SOD content in the liver tissue of the model group mice (14.711 U / mg prot) decreased by 52.29%, significantly lower than that in the blank control group (P<0.01). Compared with the model group, the SOD content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar all showed an increasing trend, increasing by 37.11%, 61.88%, and 80.19%, respectively, all with significant differences (P<0.05, P<0.01, P<0.01). Compared with the blank control group, the SOD content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar (20.169 U / mg prot, 23.813 U / mg prot, 26.508 U / mg prot) decreased by 34.59%, 22.78%, and 14.04%, respectively, all with significant differences (P<0.01, P<0.01, P<0.05).

[0078] Figure 8 The results showed that the GSH level in the model group of mouse liver tissue was 23.29% lower than that in the control group, with a significant difference (P<0.01). Compared with the model group, the GSH content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar all showed an increasing trend, increasing by 22.84%, 15.18%, and 25.02%, respectively, with significant differences (P<0.01, P<0.05, P<0.01). Compared with the blank control group, the GSH content in the low, medium, and high dose groups of Codonopsis pilosula compound fruit vinegar (10.716 U / mgprot, 10.047 U / mgprot, and 10.906 U / mgprot) was not significantly different from that in the blank control group (P>0.05).

[0079] 5.5 Effects of Codonopsis pilosula compound fruit vinegar on pathological changes in mouse liver tissue

[0080] The effects of each treatment group on pathological changes in mouse liver tissue are as follows: Figure 9 As shown.

[0081] Figure 9 The results showed that the blank control group had normal morphology and structure, while the model group exhibited liver tissue damage and structural disorder, indicating that alcohol-induced lipid metabolism abnormalities in hepatocytes. The liver tissue damage in mice was improved in each dose group of the Codonopsis pilosula compound fruit vinegar. The experimental results indicate that Codonopsis pilosula compound fruit vinegar can alleviate liver damage induced by short-term alcohol intake in mice and has a preventive effect.

[0082] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. The use of a Codonopsis lanceolata composite fruit vinegar in the preparation of a drug for the prevention and treatment of acute liver injury, characterized in that, The Codonopsis pilosula compound fruit vinegar is first prepared by a compound liquid consisting of 20-30% by weight Codonopsis pilosula extract, 15-25% by weight Pueraria lobata extract, 5-15% by weight Hovenia dulcis extract and 40-50% by weight apple juice. Then, it is fermented by alcohol and acetic acid to obtain a fermentation liquid, and finally clarified by pectinase solvent. The extract of Codonopsis pilosula is prepared by soaking Codonopsis pilosula slices in 5-7 times their weight of water for 5-7 hours, then juicing, pulping, and filtering. The extract of Pueraria lobata is prepared by adding 14-16 times their weight of water to Pueraria lobata, water bathing at 75-85℃ for 25-35 minutes, cooling to room temperature, juicing, pulping, and filtering at a weight ratio of raw material:water = 1:(14-16). The extract of Hovenia dulcis is prepared by adding 9-11 times their weight of water to crushed Hovenia dulcis, water bathing at 75-85℃ for 25-35 minutes, cooling to room temperature, juicing, pulping, and filtering at a weight ratio of raw material:water = 1:(9-11). The apple extract is prepared by peeling apples, adding 4-6 times their weight of water, and juicing. The alcoholic fermentation process is as follows: yeast is added to a sucrose solution with a mass percentage of 4-6% for activation. After activation, it is mixed evenly with the compound solution and fermented for 6-8 days. The yeast inoculum amount is 0.6-1.0%; the fermentation temperature is 28-32℃; the apparent sugar content is 16-20%; and the initial pH value is 2.5-3.

5. The acetic acid fermentation process is as follows: after the alcoholic fermentation is completed, acetic acid bacteria are poured into the fermentation broth and cultured in a constant temperature shaking incubator for 6-8 days; wherein the inoculation amount of acetic acid bacteria is 0.6-1.2%; the fermentation temperature is 28-32℃; the rotation speed of the constant temperature shaking incubator is 110-130 r / min; and the initial pH value is 4.5-5.

5. The pectinase solvent is prepared by mixing pectinase and water in a weight ratio of 1:(8~12); the method of using the pectinase solvent is to add 0.8~1.2mL of the pectinase solvent to every 4.5~5.5L of the fermentation broth.

2. Use according to claim 1, characterized in that, The mixed mass percentages of the Codonopsis pilosula extract, the Pueraria lobata extract, the Hovenia dulcis extract, and the apple extract are 25%, 20%, 10%, and 45%, respectively.

3. Use according to claim 2, characterized in that, The yeast inoculum was 1.0%; the fermentation temperature was 30℃; the apparent sugar content was 20%; and the initial pH was 3.

0.

4. Use according to claim 3, characterized in that, The inoculum size of the acetic acid bacteria was 0.9%; the fermentation temperature was 30℃; the rotation speed of the constant temperature shaking incubator was 120 r / min; and the initial pH value was 4.

5.

5. Use according to claim 4, characterized in that, The pectinase solvent is prepared by mixing pectinase and water at a weight ratio of 1:10; the method of using the pectinase solvent is as follows: add 1 mL of the pectinase solvent to every 5 L of the fermentation broth.

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