Application of ginsenoside Rg3 in preparation of medicine for preventing, treating and / or improving alcoholic fatty liver

Abstract

The invention provides application of ginsenoside Rg3 in preparation of a medicine for preventing, treating and / or improving alcoholic fatty liver, and belongs to the technical field of biological medicine. The invention provides application of ginsenoside Rg3 in preparation of a medicine for preventing, treating and / or improving alcoholic fatty liver. Ginsenoside Rg3 can accelerate alcohol metabolism, reduce accumulation of ethanol and acetaldehyde in a body and inhibit alcohol-induced lipid accumulation, oxidative stress and inflammatory response, so that the alcoholic fatty liver is effectively prevented, treated and improved.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to the use of ginsenoside Rg3 in preparing a medicament for preventing, treating and / or improving alcoholic fatty liver. Background Art

[0002] Alcoholic fatty liver is a liver disease caused by long-term and heavy drinking. It is mainly manifested by excessive accumulation of fat in liver cells, which affects liver health.

[0003] Currently, the most effective means of preventing and treating alcoholic fatty liver is still to quit drinking, and the clinically available drugs are very limited. Summary of the Invention

[0004] The purpose of the present invention is to provide the use of ginsenoside Rg3 in the preparation of a medicament for preventing, treating and / or improving alcoholic fatty liver, thereby providing a new treatment for alcoholic fatty liver.

[0005] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for preventing, treating and / or improving alcoholic fatty liver.

[0006] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for accelerating alcohol metabolism.

[0007] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for reducing the accumulation of ethanol and acetaldehyde in the body.

[0008] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for inhibiting alcohol-induced lipid accumulation, oxidative stress and / or inflammatory response.

[0009] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for protecting alcoholic liver damage.

[0010] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for alleviating alcohol-induced weight loss.

[0011] Preferably, the dosage form of the drug is an injection.

[0012] Preferably, the injection is an intraperitoneal injection.

[0013] Preferably, the drug is a unit-dose preparation; the content of ginsenoside Rg3 in the unit-dose preparation is 2.5 to 10 mg.

[0014] Preferably, based on administration to mice, the dosage of ginsenoside Rg3 is 2.5-10 mg / kg.

[0015] The present invention provides the use of ginsenoside Rg3 in the preparation of a medicament for preventing, treating, and / or ameliorating alcoholic fatty liver disease. Ginsenoside Rg3 accelerates alcohol metabolism, reduces the accumulation of ethanol and acetaldehyde in the body, and inhibits alcohol-induced lipid accumulation, oxidative stress, and inflammatory responses, thereby effectively preventing, treating, and ameliorating alcoholic fatty liver disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0017] Figure 1 The weight changes of mice in each group;

[0018] Figure 2 The appearance of liver tissues of mice in each group;

[0019] Figure 3 The lipid accumulation of mice in each group;

[0020] Figure 4 The liver damage of mice in each group;

[0021] Figure 5 Western blot results of mice in each group;

[0022] Figure 6 is the strip grayscale analysis result;

[0023] Figure 7 The immunohistochemical staining results of CYP2E1;

[0024] Figure 8 Inflammation status of mice in each group;

[0025] Figure 9 The oxidative stress status of mice in each group. DETAILED DESCRIPTION

[0026] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for preventing, treating and / or improving alcoholic fatty liver.

[0027] Ginsenoside Rg3 has no significant toxic side effects, and has not been found to be mutagenic, embryotoxic, or teratogenic. Furthermore, ginsenoside Rg3 has passed Phase IV clinical trials and is available as a prescription drug.

[0028] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for accelerating alcohol metabolism.

[0029] In the present invention, the acceleration of alcohol metabolism includes achieving it by promoting the expression of enzymes related to ethanol metabolism; the enzymes related to ethanol metabolism include at least one of ADH1, CYP2E1 and ALDH2.

[0030] Ginsenoside Rg3 can significantly regulate the expression of ethanol metabolism-related enzymes ADH1, CYP2E1 and ALDH2, and promote ethanol oxidative metabolism.

[0031] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for reducing the accumulation of ethanol and acetaldehyde in the body.

[0032] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for inhibiting alcohol-induced lipid accumulation, oxidative stress and / or inflammatory response.

[0033] As an embodiment, the inhibition of alcohol-induced inflammatory response includes reducing serum and / or liver tissue inflammation levels; the reduction of serum and / or liver tissue inflammation levels is achieved by downregulating the pro-inflammatory response of TNF-α and IL-6 and / or increasing the expression of IL-10 anti-inflammatory factor.

[0034] As an embodiment, the inhibition of alcohol-induced oxidative stress is achieved by reducing MDA content and increasing SOD and / or GSH levels.

[0035] In the present invention, ginsenoside Rg3 can effectively alleviate alcohol-induced liver fat deposition and has a good protective effect on lipid metabolism. In addition, ginsenoside Rg3 can effectively alleviate alcohol-induced fatty liver hepatitis in mice, and exert anti-inflammatory and liver protective effects by improving liver tissue morphology, reducing NAS scores and liver enzyme levels. In addition, ginsenoside Rg3 can effectively regulate the abnormal expression of inflammatory factors induced by alcohol, which is manifested by downregulating the pro-inflammatory response of TNF-α and IL-6, while significantly increasing the expression of IL-10 anti-inflammatory factors. This effect is reflected in both serum and liver tissue. Rg3 shows potential immunomodulatory function in alleviating inflammatory responses associated with alcoholic fatty liver disease. Ginsenoside Rg3 can effectively improve the oxidative stress state of mouse liver tissue induced by ethanol.

[0036] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for protecting alcoholic liver damage.

[0037] In the present invention, ginsenoside Rg3 can improve alcohol-induced hepatic steatosis.

[0038] The present invention provides the use of ginsenoside Rg3 in preparing a medicine for alleviating alcohol-induced weight loss.

[0039] Ginsenoside Rg3 can alleviate alcohol-induced weight loss and has the potential to improve the signs of alcoholic steatohepatitis.

[0040] As an embodiment, the dosage form of the drug is an injection.

[0041] As an embodiment, the injection is an intraperitoneal injection.

[0042] As an embodiment, the drug is a unit-dose preparation; the content of ginsenoside Rg3 in the unit-dose preparation is 2.5 to 10 mg.

[0043] As an embodiment, based on administration to mice, the dosage of ginsenoside Rg3 is 2.5 to 10 mg / kg.

[0044] As an embodiment, the ginsenoside Rg3 has a purity greater than or equal to 98%, is commercially available, is dissolved in distilled water, and is administered to mice by intraperitoneal injection.

[0045] To further illustrate the present invention, the application of ginsenoside Rg3 provided by the present invention in the preparation of a medicament for preventing, treating and / or improving alcoholic fatty liver disease is described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0046] Test Example 1

[0047] 1. Animal efficacy test:

[0048] Mouse model of chronic alcohol feeding plus acute alcohol gavage:

[0049] Forty male C57BL / 6 mice were acclimated to a control Lieber-DeCarli diet for 5 days after a one-week acclimation period. The mice were then acclimated to a liquid diet and tube feeding. The mice were then divided into the following groups: a pair-fed control group, a NIAAA (mouse model of chronic and binge ethanol feeding) group (EtOH), a low-dose Rg3 group (Rg3_L, 2.5 mg / kg), a high-dose Rg3 group (Rg3_H, 10 mg / kg), and a positive drug group (Silyb, silybin 25 mg / kg), with 8 mice in each group.

[0050] The EtOH group was fed with an EthanolLieber-DeCarli alcohol diet (containing 5% (vol / vol) ethanol) ad libitum for 10 days. On the 11th day, they were gavaged with a large dose of 31.5% (vol / vol) ethanol aqueous solution (5 g / kg) in the early morning.

[0051] The pair-fed group was fed a control diet (equicaloric to the EthanolLieber-DeCarli alcohol diet) for 10 days and, on the 11th day, was gavaged with maltodextrin (equicaloric to a large dose of ethanol) in the early morning;

[0052] The Rg3_L group was treated with EtOH, and Rg3 was intraperitoneally injected on the first day of alcohol feeding, once a day, with an injection dose of 2.5 mg / kg;

[0053] The Rg3_H group was treated with EtOH, and Rg3 was intraperitoneally injected on the first day of alcohol feeding, once a day, with an injection dose of 10 mg / kg;

[0054] The Silyb group was treated with the EtOH group. Starting from the first day of alcohol feeding, the mice were intraperitoneally injected with Silyb once a day at a dose of 25 mg / kg.

[0055] The weight changes of mice in each group were dynamically monitored during the modeling period. Figure 1 As shown, the control group (pair-fed) gradually gained weight, showing a normal physiological fluctuation. In the model group (EtOH), after a brief initial increase in weight following alcohol feeding, the weight decreased significantly and then remained at a low level, suggesting a weight-suppressing effect of alcohol intervention. In contrast, treatment with ginsenoside Rg3 significantly alleviated the weight loss trend in both the low-dose (Rg3_L) and high-dose (Rg3_H) groups, particularly between days 10 and 14, when weight recovery was evident. Silybin (Silyb), a positive control group, also exhibited some weight-protective effects, but this was slightly less pronounced than in the Rg3_H group. These results indicate that continuous alcohol feeding significantly inhibited weight gain in mice, successfully inducing an alcoholic steatohepatitis phenotype. Ginsenoside Rg3 alleviated weight loss in a dose-dependent manner, with the high-dose group exhibiting a more pronounced effect, approaching that of the positive control group, Silybin, suggesting its potential to improve the signs of alcoholic steatohepatitis.

[0056] Nine hours after gavage with a high-dose of ethanol or isocaloric maltodextrin, mice in each group were euthanized, and blood and organs were collected for analysis of liver tissue appearance, lipid accumulation, liver damage, alcohol metabolism enzymes, inflammation, and oxidative stress.

[0057] The appearance of the liver tissue of mice in each group can be found in Figure 2Macroscopic observation revealed that the livers of the control group (Pair-fed) were normal in size, firm in texture, and dark red in color. The livers of the model group (EtOH) were significantly enlarged, soft, and light yellow in texture, indicating severe fatty degeneration. The livers of the low-dose group (Rg3_L) showed improved appearance compared to the EtOH group, with a slightly smaller size and slightly darker color. The livers of the high-dose group (Rg3_H) showed near-normal morphology, with significant restoration of color and texture, suggesting that high-dose ginsenoside Rg3 intervention was more effective. The results indicate that ginsenoside Rg3 can improve alcohol-induced hepatic fatty degeneration in mice in a dose-dependent manner.

[0058] The lipid accumulation of mice in each group can be found in Figure 3 As shown in Table 1, Oil Red O staining showed that compared with the control group (Pair-fed), the model group (EtOH) mice had a large accumulation of lipid droplets in the liver tissue, and the red-stained area was significantly increased, indicating that alcohol intake induced significant hepatic steatosis. Compared with the EtOH group, the lipid droplet accumulation in the low-dose group (Rg3_L) and the high-dose group (Rg3_H) was significantly reduced, especially in the high-dose group, which was closer to the Pair-fed group. Quantitative results further confirmed that Rg3 intervention significantly reduced triglyceride (TG) lipid content in liver tissue and serum in a dose-dependent manner; and the Rg3 treatment effect in serum indicators was comparable to that of the positive control group silybin. The results showed that ginsenoside Rg3 can effectively alleviate alcohol-induced hepatic fat deposition and has a good dose-dependent lipid metabolism protective effect.

[0059] Table 1 Lipid accumulation in mice in each group

[0060] Group Relative area of lipid droplets Serum TG (mmol / L) Liver TG (mmol / gprot) Pair-fed 1.00±0.79 0.73±0.20 0.09±0.01 EtOH 17.22±5.90 1.36±0.26 0.36±0.05 Rg3_L 9.89±2.17 0.87±0.22 0.24±0.06 Rg3_H 7.14±2.71 0.81±0.26 0.23±0.04 Silyb —— 0.65±0.25 ——

[0061] The liver damage of mice in each group can be found in Figure 4 As shown in Table 2, HE staining results showed that the liver tissue of mice in the model group (EtOH) showed obvious fatty degeneration and inflammatory cell infiltration. Compared with the blank control group (Pair-fed), the NAS score was significantly increased, and the serum ALT and AST levels were significantly increased, indicating that the alcoholic steatohepatitis model was successfully established. Compared with the EtOH group, the low-dose Rg3 group (Rg3_L) partially alleviated liver tissue damage, while the high-dose group (Rg3_H) significantly improved liver tissue structure, reduced NAS scores and ALT and AST levels, showing a dose-dependent protective effect. These results indicate that ginsenoside Rg3 can effectively alleviate alcohol-induced steatohepatitis in mice, exerting anti-inflammatory and liver-protective effects by improving liver tissue morphology, reducing NAS scores and liver enzyme levels.

[0062] Table 2 Protective effect on the liver of mice in each group

[0063] Group Nonalcoholic fatty liver disease score Serum ALT (U / L) Serum AST (U / L) Pair-fed 0.56±0.53 21.03±0.96 108.72±3.72 EtOH 3.67±0.87 91.25±8.77 208.85±11.11 Rg3_L 2.56±0.53 51.15±13.67 162.65±25.51 Rg3_H 2.00±0.50 34.18±5.04 129.52±12.58 Silyb —— 38.75±7.27 160.68±27.14

[0064] The results of alcohol metabolism enzyme detection in each group of mice are shown in Figures 5 to 7 And Table 3. In the process of ethanol metabolism, ADH1 is the main metabolic enzyme, catalyzing the oxidation of ethanol to acetaldehyde. CYP2E1 serves as an auxiliary pathway for ethanol metabolism. Its expression is significantly upregulated under conditions of chronic or high-dose ethanol exposure. It participates in the oxidative metabolism of ethanol and also produces acetaldehyde. ALDH2 catalyzes the further conversion of acetaldehyde into acetic acid and participates in the detoxification process of ethanol metabolism. The above three enzymes play a key role in the occurrence and development of alcoholic fatty liver disease. The disorder of their expression levels is one of the important mechanisms that cause abnormal liver function, inflammatory response and cell damage. Figure 5 As shown in the figure, the results of Western blot showed that compared with the control group (Pair-fed), the expressions of ADH1, CYP2E1 and ALDH2 proteins in the liver tissues of the model group (EtOH) and the Rg3-treated group were upregulated to varying degrees. Figure 6 The results of band grayscale analysis showed that the expression levels of ADH1, CYP2E1 and ALDH2 proteins showed an increasing trend in the EtOH group, and were further upregulated in a dose-dependent manner after Rg3 intervention. Compared with the model group (EtOH), the protein expression level in the high-dose group (Rg3_H) showed an increase, suggesting that ginsenoside Rg3 can further enhance the expression of liver ethanol metabolism-related enzymes. Figure 7 Immunohistochemical staining of CYP2E1 revealed enhanced CYP2E1 expression in the model group (EtOH), primarily distributed in the hepatocyte cytoplasm. CYP2E1 staining intensity in the low-dose group (Rg3_L) was further enhanced compared to the EtOH group, with the Rg3_H group displaying the strongest positive expression and a more widespread distribution. This confirmed the Western blot results, indicating that Rg3 can promote CYP2E1 protein expression. The results showed that ginsenoside Rg3 significantly modulated the expression of enzymes involved in ethanol metabolism, promoting the expression of ADH1, CYP2E1, and ALDH2 in a mouse model of alcoholic steatohepatitis in a dose-dependent manner. CYP2E1 immunohistochemical results also showed the strongest positive expression in the high-dose Rg3 group, further confirming Rg3's potential to promote ethanol oxidative metabolism. These results suggest that ginsenoside Rg3 alleviates alcohol-induced liver damage by enhancing ethanol metabolic pathways.

[0065] Table 3 Alcohol metabolizing enzymes in each group of mice

[0066] Group ADH1 CYP2E1 ALDH2 Pair-fed 1.00±0.19 1.00±0.23 1.00±0.16 EtOH 1.21±0.27 3.16±0.66 2.28±0.27 Rg3_L 1.52±0.28 3.83±0.59 2.58±0.32 Rg3_H 2.25±0.18 4.92±0.45 3.53±0.22

[0067] The inflammation status of mice in each group can be found in Figure 8, Table 4 and Table 5. The results showed that compared with the control group (Pair-fed), the levels of TNF-α and IL-6 in the serum and liver tissue of the model group (EtOH) mice were significantly increased, and the level of IL-10 was significantly decreased, indicating that alcohol induced a significant pro-inflammatory response and inhibition of anti-inflammatory ability. After intervention with ginsenoside Rg3, the low-dose group (Rg3_L) showed a downward trend in the expression of TNF-α and IL-6, and the level of IL-10 increased slightly, while the high-dose group (Rg3_H) showed more significant improvements in the above indicators, showing a dose-dependent regulation trend. The results showed that ginsenoside Rg3 can effectively regulate the abnormal expression of inflammatory factors induced by ethanol, manifested as downregulating the pro-inflammatory response of TNF-α and IL-6, while significantly increasing the expression of IL-10 anti-inflammatory factors. This effect was reflected in both serum and liver tissue. Rg3 shows potential immunomodulatory function in alleviating the inflammatory response associated with alcoholic fatty liver disease.

[0068] Table 4 Serum inflammatory indicators of mice in each group

[0069] Group IL-6 TNF-α IL-10 Pair-fed 5.96±2.42 9.16±1.02 22.17±2.20 EtOH 94.38±39.89 25.70±7.24 28.16±3.58 Rg3_L 35.28±28.79 14.31±4.48 32.60±6.68 Rg3_H 18.00±12.35 11.59±2.13 37.76±6.98

[0070] Table 5 Liver inflammation indicators of mice in each group

[0071] Group IL-6 TNF-α IL-10 Pair-fed 4.11±1.02 4.63±0.42 37.77±12.27 EtOH 8.21±2.39 26.19±8.06 17.86±3.98 Rg3_L 5.10±1.00 13.84±9.69 23.94±7.66 Rg3_H 4.48±0.56 8.54±5.95 30.98±8.84

[0072] The oxidative stress of mice in each group can be found in Figure 9 and Table 6. As shown in the figure, MDA content in the liver tissue of mice in the model group (EtOH) was significantly increased, while SOD and GSH levels were significantly decreased, indicating that ethanol intake caused significant oxidative stress damage. After intervention with ginsenoside Rg3, oxidative stress indicators in the low-dose Rg3 group (Rg3_L) improved compared with the model group. The high-dose group (Rg3_H) showed a more significant regulatory effect, with a significant decrease in MDA content and a significant increase in SOD and GSH levels, showing a dose-dependent trend. These results indicate that ginsenoside Rg3 can effectively improve ethanol-induced oxidative stress in mouse liver tissue.

[0073] Table 6 Oxidative stress in mice in each group

[0074] Group GSH T-SOD MDA Pair-fed 11.68±2.98 336.23±26.97 0.40±0.06 EtOH 2.97±1.87 194.02±28.44 0.72±0.14 Rg3_L 8.52±0.86 268.92±18.06 0.53±0.09 Rg3_H 9.43±4.78 362.85±68.17 0.46±0.09

[0075] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. Use of ginsenoside Rg3 in the preparation of a medicament for preventing, treating and / or improving alcoholic fatty liver.

2. Application of ginsenoside Rg3 in the preparation of drugs for accelerating alcohol metabolism.

3. Application of ginsenoside Rg3 in the preparation of drugs for reducing the accumulation of ethanol and acetaldehyde in the body.

4. Use of ginsenoside Rg3 in the preparation of drugs for inhibiting alcohol-induced lipid accumulation, oxidative stress and / or inflammatory response.

5. Application of ginsenoside Rg3 in the preparation of drugs for protecting alcoholic liver damage.

6. Application of ginsenoside Rg3 in the preparation of a drug for alleviating alcohol-induced weight loss.

7. The use according to any one of claims 1 to 6, characterized in that: The dosage form of the medicine is injection.

8. The use according to claim 7, characterized in that The injection is an intraperitoneal injection.

9. The use according to any one of claims 1 to 6, characterized in that: The medicine is a unit-dose preparation; the content of ginsenoside Rg3 in the unit-dose preparation is 2.5 to 10 mg.

10. The use according to any one of claims 1 to 6, characterized in that: Based on administration to mice, the dosage of ginsenoside Rg3 is 2.5-10 mg / kg.

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