Traditional Chinese medicine composition for preventing and treating alcoholic liver disease

Abstract

The traditional Chinese medicine composition is prepared from the following components in parts by mass: 4 to 8 parts of anoectochilus roxburghii, 8 to 12 parts of flos puerariae, 4 to 8 parts of semen hoveniae, 8 to 12 parts of poria cocos and 4 to 8 parts of pericarpium citri reticulatae. According to the traditional Chinese medicine composition, through a TLR4 / NF-kappa B signal channel, liver tissue pathological damage is effectively reduced, the liver function is improved, oxidative stress is reduced, and inflammation is adjusted, so that the protection effect on alcoholic liver injury is achieved.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine composition for preventing and treating alcoholic liver disease. Background Art

[0002] Alcohol-associated liver disease (ALD) is a liver disease caused by long-term heavy drinking. With the surge in global alcohol consumption and the prevalence of alcohol culture, the incidence of ALD is increasing, becoming one of the main liver diseases that endanger the health of the Chinese people, and also a public health issue that has attracted much attention worldwide. According to statistics, the prevalence of ALD in my country is as high as 5.15%, and it is on the rise. Among the ALD population, 10% to 20% of patients eventually progress to cirrhosis, which brings great burdens to individuals and society. At present, there is a lack of effective treatment for ALD, especially severe alcoholic hepatitis, which has always been a difficulty in the treatment of ALD. At present, hormone therapy is recommended for patients with severe alcoholic hepatitis in domestic and foreign ALD guidelines.

[0003] Currently, there is a lack of effective treatment for ALD. Domestic and international guidelines recommend hormone therapy for severe alcoholic hepatitis, but hormones have many adverse reactions, including inducing and aggravating infection, causing increased blood sugar and blood pressure, causing gastrointestinal ulcers, affecting bone metabolism, etc. There are disputes about the indications and long-term benefits of hormone therapy. Therefore, there is an urgent need to find a safe and effective alternative therapy.

[0004] Traditional Chinese medicine has a long history of treating ALD. The Treatise on the Causes and Symptoms of Various Diseases mentions: "Alcohol is toxic and very hot. Drinking too much will cause toxic heat to overflow the meridians and internal organs, causing various diseases." According to Chinese medicine, alcoholic liver disease is caused by long-term and heavy drinking. The alcoholic dampness and heat damage the liver and spleen, causing the liver to fail to dredge and the spleen to fail to function properly. Qi and blood are not in harmony, phlegm and dampness are generated internally, and phlegm, dampness and heat are intertwined, eventually leading to the formation of a syndrome of deficiency in the main and excess in the superficial, or a mixture of deficiency and excess. In terms of treatment, according to the syndrome differentiation, the main treatment is to soothe the liver and regulate qi, clear away heat and detoxify. Traditional Chinese medicine has a definite therapeutic effect in the treatment of alcoholic liver disease, and at the same time has good safety, showing unique advantages. Summary of the invention

[0005] The main purpose of the present invention is to provide a Chinese medicine composition for preventing and treating alcoholic liver disease.

[0006] The technical solution adopted by the present invention to solve its technical problem is:

[0007] A traditional Chinese medicine composition for preventing and treating alcoholic liver disease comprises, by weight, 4-8 parts of anoectochilus roxburghii, 8-12 parts of kudzu flower, 4-8 parts of Hovenia dulcis, 8-12 parts of Poria cocos and 4-8 parts of dried tangerine peel.

[0008] Furthermore, the Chinese medicine composition for preventing and treating alcoholic liver disease comprises, by mass, 6 parts of Anoectochilus roxburghii, 10 parts of Pueraria lobata flower, 6 parts of Hovenia dulcis fruit, 10 parts of Poria cocos and 6 parts of dried tangerine peel.

[0009] The method for preparing the Chinese medicine composition for preventing and treating alcoholic liver disease comprises the following steps:

[0010] Weigh each component according to the above-mentioned mass proportion, and boil the above-mentioned traditional Chinese medicine composition with water to obtain a primary decoction liquid; separate the remaining part after the primary decoction liquid, including the remaining medicinal residue and the residual medicinal liquid, and boil it again with water to obtain a secondary decoction liquid; combine the primary decoction liquid and the secondary decoction liquid to obtain.

[0011] Furthermore, the volume of water added in the first decoction and the second decoction is 5-15 times the volume of the raw material, respectively.

[0012] Furthermore, the above-mentioned Chinese medicine composition is boiled over high heat and then decocted over low heat for 25-35 minutes.

[0013] Furthermore, each dose of the Chinese medicine composition is equivalent to 30-50g of the raw material medicine.

[0014] Furthermore, the volume of the combined decoction is 160 to 240 mL per dose.

[0015] The present invention also provides use of the traditional Chinese medicine composition in preparing medicine for treating alcoholic liver disease.

[0016] Furthermore, the dosage form of the drug is an oral preparation.

[0017] Furthermore, the oral preparation includes a mixture, granules, tablets, pills or capsules.

[0018] Compared with the background technology, this technical solution has the following advantages:

[0019] The Chinese medicine composition of the present invention effectively reduces liver tissue pathological damage, improves liver function, reduces oxidative stress and regulates inflammation through the TLR4 / NF-κB signaling pathway, thereby playing a protective role against alcoholic liver damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0021] Figure 1 Pathological sections of liver tissue (H&E staining ×400). (A) Control group (B) Model group (C) Low-dose Jinge Fang group (D) High-dose Jinge Fang group.

[0022] Figure 2.Effects of JGF on liver function of ALD mice. (A) ALT in serum. (B) AST in serum. All data are expressed as mean ± standard deviation. Note: **p<0.01, ****p<0.0001 compared with the control group, #p<0.05, ##p<0.01 compared with the model group.

[0023] Figure 3 Comparison of oxidative stress levels in liver tissue and serum of rats in each groupComparison with the control group*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; compared with the model group#P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0024] Figure 4 Comparison of inflammatory cytokine levels in liver tissue and serum of rats in each group compared with those in the control group *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; compared with those in the model group #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001.

[0025] Figure 5 Effect of JGF on the expression of TLR4, NF-κB p65, and p-NF-κB p65 proteins in the liver of ALD mice (A) Expression levels of TLR4, NF-κB p65, and p-NF-κB p65. (B) Relative expression of TLR4. (C) Relative expression of NF-κB p65. (D) Relative expression of p-NF-κB p65. All data are expressed as mean ± standard deviation. Note: *p<0.05, ***p<0.001, compared with the control group ****p<0.0001, ###p<0.001, compared with the model group ####p<0.0001. DETAILED DESCRIPTION

[0026] Example 1

[0027] A Chinese medicine composition for preventing and treating alcoholic liver disease (hereinafter referred to as Jinge Fang or JGF), comprising the following raw materials by weight: 6g of Anoectochilus roxburghii, 10g of Pueraria lobata flower, 6g of Hovenia dulcis fruit, 10g of Poria cocos and 6g of dried tangerine peel.

[0028] The specific steps of the preparation method are as follows:

[0029] Soak the weighed medicinal materials in water for 30 minutes. For the first extraction, add 10 times the volume of water, boil over high heat, then simmer for 0.5 hours, and filter. For the second extraction of the residue, add 8 times the volume of water, boil over high heat, then simmer for 0.5 hours. Filter the mixture, mix the filtrate, and concentrate to the desired drug concentration level.

[0030] In a specific example, the concentration was about 0.21 g of API / ml in the low-dose group and 0.42 g of API / ml in the high-dose group.

[0031] Example 2

[0032] A traditional Chinese medicine composition for preventing and treating alcoholic liver disease comprises the following raw materials by weight: 4g of anoectochilus roxburghii, 12g of kudzu flower, 4g of Hovenia dulcis fruit, 12g of Poria cocos and 4g of dried tangerine peel.

[0033] The specific steps of the preparation method are as follows:

[0034] Soak the weighed medicinal materials in water for 30 minutes. For the first extraction, add 10 times the volume of water, boil over high heat, then simmer for 0.5 hours, and filter. For the second extraction of the residue, add 8 times the volume of water, boil over high heat, then simmer for 0.5 hours. Filter the mixture, mix the filtrate, and concentrate to the desired drug concentration level.

[0035] Example 3

[0036] A traditional Chinese medicine composition for preventing and treating alcoholic liver disease comprises the following raw materials by weight: 8g of anoectochilus roxburghii, 8g of kudzu flower, 4g of Hovenia dulcis fruit, 8g of Poria cocos and 4g of dried tangerine peel.

[0037] The specific steps of the preparation method are as follows:

[0038] Soak the weighed medicinal materials in water for 30 minutes. For the first extraction, add 10 times the volume of water, boil over high heat, then simmer for 0.5 hours, and filter. For the second extraction of the residue, add 8 times the volume of water, boil over high heat, then simmer for 0.5 hours. Filter the mixture, mix the filtrate, and concentrate to the desired drug concentration level.

[0039] Effect Experiment

[0040] 1. Research Methods

[0041] (1) Experimental animals, model preparation, and grouping

[0042] Forty male SD rats (200±20g) were randomly divided into 4 groups, with 10 rats in each group. The groups were control group, model group, low-dose Jinge Fang group (2.1g / kg), and high-dose Jinge Fang group (4.2g / kg). The model was prepared by feeding with Liber-DeCarli alcohol liquid feed. Each rat was gavaged with a dose of 10ml / kg of the specified solution once a day for 8 weeks. The control group and the model group were gavaged with an equal amount of distilled water.

[0043] (2) Specimen collection and processing

[0044] Blood: 24 hours after the last treatment, blood was collected from the rats in each group through the heart, centrifuged, and the supernatant was collected and stored in a -80°C refrigerator for later use.

[0045] Liver tissue: 24 hours after the last treatment, rats in each group were anesthetized with 2% sodium pentobarbital and then laparotomized on a sterile operating table to remove the complete liver. A portion was cut for pathological observation, and the rest was prepared into tissue homogenate, centrifuged, and the supernatant was taken and stored in a -80℃ refrigerator for later use.

[0046] (3) Detection indicators and methods

[0047] A. HE staining was used to observe the pathological changes of liver tissue under an optical microscope.

[0048] B. Biochemical analysis was used to determine the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats.

[0049] C. ELISA was used to detect the oxidative stress indicators of rats, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); ELISA was used to detect the levels of inflammatory cytokines in rats, including tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and IL-1β.

[0050] D. Western blot was used to detect the expression of TLR4, NF-κB p65 and p-NF-κB p65 proteins.

[0051] 2. Experimental results

[0052] 2.1 Pathological results

[0053] Figure 1 The results showed that the liver of the control group had no obvious fatty degeneration and showed a typical lobular structure, with hepatocyte cords radiating around the central vein. However, in the model group, the liver showed extensive fatty degeneration and the cells were balloon-like. In the low-dose and high-dose groups, the liver tissue also did not show obvious fatty degeneration and retained the normal lobular structure.

[0054] 2.2 Liver function results

[0055] The experimental results are as follows Figure 2The results showed that the ALT and AST levels in the model group were significantly higher than those in the control group (P<0.0001, P<0.01). The ALT level in the low-dose group was significantly lower than that in the model group (P<0.05). The AST level only decreased slightly, and the difference was not statistically significant (P<0.05). The ALT and AST levels in the high-dose group were significantly lower than those in the control group (P<0.01). These results indicate that JGF has a significant therapeutic effect on ALD.

[0056] 2.3 Oxidative stress results

[0057] like Figure 3 As shown in the results, compared with the control group, the MDA levels in the plasma and liver tissue of the rats in the model group were significantly increased (P<0.001, P<0.0001), and the SOD and GSH-Px levels were significantly decreased (P<0.01, P<0.001, P<0.0001, P<0.0001). Compared with the model group, the MDA levels in the plasma and liver tissue of the rats in the low-dose and high-dose drug groups were significantly decreased (P<0.001, P<0.001, P<0.0001, P<0.0001). The SOD and GSH-Px levels in the plasma and liver tissue of the rats in each group were significantly increased (P<0.05, P<0.05, P<0.05, P<0.05, P<0.05, P<0.0001, P<0.0001, P<0.05, P<0.01). This suggests that JGF can improve the oxidative stress level in rats with alcoholic liver injury.

[0058] 2.4 Inflammatory cytokine results

[0059] Figure 4 The results showed that compared with the control group, the levels of TNF-α, IL-1β, and IL-6 in plasma and liver tissue of rats in the model group were significantly increased (P<0.05, P<0.01, P<0.001, P<0.001, P<0.0001, P<0.001). The levels of TNF-α, IL-1β, and IL-6 in serum of rats in the low- and high-dose drug groups were significantly lower than those in the model group (P<0.01, P<0.01, P<0.05, P<0.01, P<0.01, P<0.01, P<0.05, P<0.01, P<0.05, P<0.05, P<0.05, P<0.05, P<0.01).

[0060] 2.5 Effect of Jinge Fang on TLR4 / NF-κB signaling pathway

[0061] like Figure 5The results showed that the expression levels of TLR4, NF-κB p65, and P-NF-κB p65 proteins in the liver tissue of the rats in the model group were significantly higher than those in the control group (P<0.0001, P<0.05, P<0.001). Compared with the model group, the expression levels of TLR4, NF-κB p65, and P-NF-κB p65 in the liver tissue of the rats in the low-dose and high-dose groups were significantly decreased (P<0.0001, P<0.0001, P<0.001, P<0.0001, P<0.001, P<0.001).

[0062] In summary, the Jinge prescription of the present invention effectively reduces liver tissue pathological damage, improves liver function, reduces oxidative stress and regulates inflammation through the TLR4 / NF-κB signaling pathway, thereby playing a protective role against alcoholic liver damage.

[0063] The above description is only a preferred embodiment of the present invention, and therefore cannot be used to limit the scope of the present invention. That is, equivalent changes and modifications made according to the patent scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A Chinese medicine composition for preventing and treating alcoholic liver disease, characterized in that: The ingredients include 4-8 parts of anoectochilus roxburghii, 8-12 parts of kudzu vine flowers, 4-8 parts of Hovenia dulcis seeds, 8-12 parts of Poria cocos and 4-8 parts of dried tangerine peel, by weight.

2. A Chinese medicine composition for preventing and treating alcoholic liver disease according to claim 1, characterized in that: The ingredients include 6 parts of Anoectochilus roxburghii, 10 parts of Pueraria lobata flower, 6 parts of Hovenia dulcis fruit, 10 parts of Poria cocos and 6 parts of dried orange peel, by weight.

3. A method for preparing a Chinese medicine composition for preventing and treating alcoholic liver disease according to claim 1 or 2, comprising the following steps: weighing each component according to a ratio, decocting the Chinese medicine composition with water to obtain a primary decoction; separating the remaining part of the primary decoction, including the remaining drug residue and the residual drug liquid, decocting again with water to obtain a secondary decoction; combining the primary decoction and the secondary decoction to obtain.

4. The method for preparing the Chinese medicine composition according to claim 3, characterized in that: The Chinese medicine composition is boiled over high heat and then decocted over low heat for 25-35 minutes.

5. The method for preparing the Chinese medicine composition according to claim 3, characterized in that: The volume of water added in the first decoction and the second decoction is 5-15 times the volume of the raw material respectively.

6. A Chinese medicine composition for preventing and treating alcoholic liver disease according to claim 3, characterized in that: Each dose of the Chinese medicine composition is equivalent to 30-50g of the raw material medicine.

7. The method for preparing the Chinese medicine composition according to claim 6, characterized in that: The volume of the combined decoction is 160-240 mL per dose.

8. Use of the Chinese medicine composition according to any one of claims 1 or 2 in the preparation of a medicament for treating alcoholic liver disease.

9. The use according to claim 8, characterized in that: The dosage form of the drug is an oral preparation.

10. The use according to claim 9, characterized in that: The oral preparations include mixtures, granules, tablets, pills or capsules.

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