CN116270682A - Ginsenoside Rg 1 Application of medicine in preparation of medicine for treating alcoholic liver injury - Google Patents

Ginsenoside Rg 1 Application of medicine in preparation of medicine for treating alcoholic liver injury Download PDF

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Publication number
CN116270682A
CN116270682A CN202310299683.4A CN202310299683A CN116270682A CN 116270682 A CN116270682 A CN 116270682A CN 202310299683 A CN202310299683 A CN 202310299683A CN 116270682 A CN116270682 A CN 116270682A
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Prior art keywords
ginsenoside
liver injury
alcoholic liver
treating alcoholic
medicine
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CN202310299683.4A
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Chinese (zh)
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李志满
孙印石
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Institute Special Animal and Plant Sciences CAAS
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Institute Special Animal and Plant Sciences CAAS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention discloses a ginsenoside Rg 1 An application in preparing a medicament for treating alcoholic liver injury belongs to the field of medicaments. The invention uses ginsenoside Rg 1 For treating alcoholic liver injury, specifically ginsenoside Rg 1 Use of ginsenoside Rg for improving alcoholic liver injury by inhibiting NLRP3 inflammatory body/caspase-1 signaling pathway 1 After administration, the fatty degeneration of the liver of the organism is reduced, and the contents of transaminase indexes AST, ALT and TG in serum are obviously reduced, which indicates that ginsenoside Rg1 can improve alcoholic liver injury.

Description

Ginsenoside Rg 1 Application of medicine in preparation of medicine for treating alcoholic liver injury
Technical Field
The invention relates to a ginsenoside Rg 1 An application in preparing a medicament for treating alcoholic liver injury belongs to the field of medicaments.
Background
Alcoholic liver injury is a common liver disease, a complex pro-inflammatory process that can lead to steatosis, alcoholic hepatitis, fibrosis, and ultimately cirrhosis. About up to 90% of severe drinkers (ethanol consumption >60 g/day) experience steatosis, with about 35% experiencing more severe alcoholic liver disease. Alcoholic fatty liver is generally asymptomatic and has long been considered benign because it may reverse completely after about 4-6 weeks. However, some studies indicate that 5-15% of alcoholic fatty liver patients will continue to progress from steatosis to fibrosis and cirrhosis. Alcoholic hepatitis is characterized by inflammatory cell infiltration into the liver and hepatic cell injury, which occurs in patients with fatty liver degeneration, often associated with progressive fibrosis. Alcoholic cirrhosis is the end stage of alcoholic liver injury, endangering the life safety of the patient. The deleterious effects of ethanol on the liver have been studied for about 60 years and alcoholic liver injury is now widely recognized as a multifactorial disease, with parenchymal and non-parenchymal cells in the liver and other types of liver cells involved in the pathogenesis of alcoholic liver injury. Although treatments for alcoholic liver injury are under development, their efficacy and safety issues are limited. Therefore, the development of safe and effective drugs and foods for resisting alcoholic liver injury has important significance.
Ginseng (Panax ginseng c.a. mey.) is a dried root and rhizome of ginseng, a perennial herb of the araliaceae family, and is a valuable edible and medicinal plant. Ginsenoside is one of the main pharmacological active ingredients of Ginseng radix, wherein ginsenoside Rg 1 (Ginsenoside Rg 1 ) Is a key bioactive component. Ginsenoside Rg 1 Has various biological activities such as anti-inflammatory, antioxidant, antihypoxic, antiaging, immunity enhancing, and memory improving effects. There is also an increasing number of studies demonstrating its effective role in a variety of liver diseases.
Disclosure of Invention
One of the purposes of the present invention is to provide ginsenoside Rg 1 Application in preparing medicine for treating alcoholic liver injury is provided.
Another object of the present invention is ginsenoside Rg 1 Application in preparing medicine for treating alcoholic fatty liver.
The technical scheme of the invention is as follows:
ginsenoside Rg 1 Application in preparing medicine for treating alcoholic liver injury is provided.
Further defined, alcoholic liver injury includes acute or chronic liver injury caused by alcohol.
Further defined, the agent for treating alcoholic liver injury refers to inhibiting NLRP3 inflammatory corpuscle or caspase-1 signaling pathway.
The invention also provides a pharmaceutical composition for treating alcoholic liver injury, and the pharmaceutical composition specifically comprises ginsenoside Rg1 as an active ingredient and a pharmaceutically acceptable carrier.
Further defined, the molecular structure of ginsenoside Rg1 is as follows:
Figure BDA0004144606360000021
further defined, the pharmaceutical composition is in the form of a tablet capsule, pill, granule, powder, paste, mixture, suspension or liquid formulation.
The invention also provides a food for relieving liver injury caused by alcohol, and the food specifically contains ginsenoside Rg1.
The invention also provides a pharmaceutical compound for treating alcoholic liver injury.
The invention also provides a health care product for assisting in relieving liver injury caused by alcohol, and the health care product specifically contains ginsenoside Rg 1
The invention has the following beneficial effects: the invention uses ginsenoside Rg 1 For treating alcoholic liver injury, specifically ginsenoside Rg 1 Use of ginsenoside Rg for improving alcoholic liver injury by inhibiting NLRP3 inflammatory body/caspase-1 signaling pathway 1 After administration, the fatty degeneration of the organism liver is reduced, and the contents of transaminase indexes AST, ALT and TG in serum are obviously reduced, which indicates that ginsenoside Rg 1 Can be used for improving alcoholic liver injury.
Drawings
FIG. 1 shows the ginsenoside Rg at different doses 1 Influence on pathological changes of liver tissues of mice with acute alcoholic liver injury;
FIG. 2 shows the ginsenoside Rg at different doses 1 Effect on acute alcoholic liver injury mice NLRP3 inflammatory body/caspase-1 protein.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, methods and apparatus used, without any particular description, are those conventional in the art and are commercially available to those skilled in the art.
Example 1: the invention will be further described with reference to the accompanying drawings and specific experiments.
1. Experimental materials
1.1 laboratory animals
ICR mice were purchased from the company, inc. SCXK (Liao) 2020-0001.
1.2 drugs and Agents
Alanine aminotransferase (alanine aminotransferase, ALT), aspartate Aminotransferase (AST) and Triglyceride (TG) kits were purchased from the institute of bioengineering, build-up bioengineering, south kyo; the BCA method total protein quantitative assay kit was purchased from the bio-tech company of bi yun.
2. Experimental method
2.1 establishment of acute alcohol model
ICR mice were randomized to normal groups, alcohol group (i.e., model group), low dose group (5 mg/kg), medium dose group (10 mg/kg), high dose group (20 mg/kg) of ginsenoside Rg1, 8 per group after one week adaptation. Each treatment group was given a corresponding therapeutic drug for 7 consecutive days, 1 time per day, and normal and model groups were perfused with an equal volume of physiological saline. After 7 days, except for the normal group, the stomach is irrigated with 50% ethanol (6 g/kg) by volume fraction, and a model of acute alcoholic liver injury of the once-through fulminant mice is established. The last 1 day of administration was fasted for 12h, after 12h, the eyeballs were taken for blood collection after anesthesia with diethyl ether, and the livers were isolated and stored in a refrigerator at-80 ℃.
2.2 detection of Biochemical indicators
The serum of the mice was tested for glutamic-oxaloacetic transaminase (aspartate aminotransferase, AST), glutamic-pyruvic transaminase (alanine aminotransferase, ALT), triglyceride (TG) content.
2.3 protein imprinting method to detect the expression of proteins in liver tissue
The protein concentration of cells is measured by BCA method, SDS-PAGE (10% -12%) separation gel is used for separating the same amount of protein samples, the protein samples are transferred to PVDF membrane, the protein samples are blocked for 1h, incubated by primary antibody, and then placed overnight at 4 ℃ and incubated for 1h at room temperature by using enzyme-labeled secondary antibody. And (3) mixing the reagent A and the reagent B in equal volumes, fully contacting the PVDF film with the mixed solution, and exposing in a full-function imaging system.
2.4 statistical analysis
Data were processed using statistical analysis, experimental results
Figure BDA0004144606360000031
Data analysis was performed using Graphpad Prism5 (Graphpad software, inc, san Diego, USA) software, and data were compared using One-way anova (One-way anova) and Turkey's multifactor t-test.
3. Experimental results
3.1 Effect of ginsenoside Rg1 on alcoholic liver injury mice AST, ALT and TG
ALT and AST are main functional enzymes in liver cells, are signals of liver cell injury, and another concurrent symptom possibly caused by alcohol entering the body is lipid metabolism abnormality, so that the detection of the activity of ALT and AST and the TG content in serum can accurately reflect the degree of early alcoholic liver injury.
The results are shown in table 1 below, and the activity of ALT, AST and TG in the serum of mice in the model group were significantly increased (P <0.01, P < 0.001) compared to the normal group, indicating primarily that acute alcohol was able to induce liver injury. The ginsenoside Rg1 can obviously reduce the contents of ALT, AST and TG in serum of mice (P is less than 0.01, P is less than 0.05), which indicates that the ginsenoside Rg1 can inhibit alcoholic liver injury and reduce TG accumulation in liver.
TABLE 1 Effect of ginsenoside Rg1 on mice with acute alcoholic liver injury
Figure BDA0004144606360000041
Note that: in comparison with the normal group, ## P<0.001, compared to the model set, ** P<0.01, * P<0.05
3.2 Effect of ginsenoside Rg1 on pathological changes of liver tissue of mice with acute alcoholic liver injury
The results are shown in FIG. 1, and H & E staining results show that the normal group mice have regular arrangement of hepatic cell lines and normal morphology (normal group in FIG. 1); the presence of large numbers of white lipid droplets, fatty vacuolation, and inflammatory cell infiltration in cells in liver tissue of the ETOH group mice; the mouse liver cell lipid drop number in Rg1 group gradually decreased, and the inflammatory infiltration degree was reduced.
3.3 Effect of ginsenoside Rg1 on acute alcoholic liver injury mice NLRP3 inflammatory body/caspase-1 protein
The expression levels of NLRP3 and caspase-1 proteins are detected by adopting Westernblot, as shown in figure 1, compared with a normal group, the expression levels of NLRP3 and caspase-1 in the ETOH group are obviously increased; compared with the ETOH group, the expression level of NLRP3 and caspase-1 in liver tissues of mice in low, medium and high administration groups of Rg1 is obviously reduced, and the dosage dependency is certain.
In conclusion, ginsenoside Rg1 improves alcoholic liver injury by inhibiting NLRP3 inflammatory corpuscle/caspase-1 signal path, fatty degeneration of organism liver is reduced after ginsenoside Rg1 is dosed, and transaminase indexes AST, ALT and TG content in serum are obviously reduced, which indicates that ginsenoside Rg1 can improve alcoholic liver injury.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.

Claims (9)

1. Ginsenoside Rg 1 Application in preparing medicine for treating alcoholic liver injury is provided.
2. Ginsenoside Rg of claim 1 1 The application of the medicine for treating alcoholic liver injury is characterized in that the alcoholic liver injury comprises acute or chronic liver injury caused by alcohol.
3. Ginsenoside Rg of claim 1 1 The application of the drug for treating alcoholic liver injury in preparation of the drug for treating alcoholic liver injury is characterized in that the drug for treating alcoholic liver injury is used for inhibiting NLRP3 inflammatory corpuscle or caspase-1 signal path.
4. A pharmaceutical composition for treating alcoholic liver injury, characterized in that the pharmaceutical composition comprises ginsenoside Rg as an active ingredient 1 And a pharmaceutically acceptable carrier.
5. The pharmaceutical composition according to claim 4, wherein ginsenoside Rg 1 The molecular structure of (2) is as follows:
Figure FDA0004144606350000011
6. the pharmaceutical composition of claim 4, wherein the pharmaceutical composition is in the form of a tablet capsule, pill, granule, powder, paste, mixture, suspension, or liquid formulation.
7. A food for alleviating liver injury caused by alcohol is characterized by comprising ginsenoside Rg 1
8. Pharmaceutical compound for treating alcoholic liver injuryCharacterized in that the active ingredient of the compound has ginsenoside Rg 1 The molecular structure includes, but is not limited to, a pharmaceutically acceptable salt, ester, prodrug, solvate, polymorph, hydrate or derivative.
9. A health product for assisting in relieving liver injury caused by alcohol is characterized by comprising ginsenoside Rg 1
CN202310299683.4A 2023-03-25 2023-03-25 Ginsenoside Rg 1 Application of medicine in preparation of medicine for treating alcoholic liver injury Pending CN116270682A (en)

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