Use of isosakuranin in preparation of liver injury drugs

Abstract

The application belongs to the technical field of medicine, and particularly relates to application of isosalicine in preparation of liver injury drugs. 13 H 18 O7; molecular weight is 286.28, hereinafter referred to as IS), the drug IS does not show toxicity in the investigated concentration range (6.25-100 muM), can significantly improve the cell survival rate of liver parenchymal cells AML-12 induced by acetaminophen, has a significant liver protection effect, and has a good application prospect in preparation of drugs for preventing and treating liver injury.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, and particularly relates to application of isosalicine in preparation of liver injury drugs. BACKGROUND

[0002] The liver is the largest parenchymal organ in the human body, and bears key functions such as metabolism, immune regulation and detoxification. Viral hepatitis, alcohol and drug toxic liver disease, liver damage of systemic diseases and the resulting liver fibrosis, liver cirrhosis, liver failure and the like have become common diseases that seriously endanger human health. Chemical liver injury refers to liver injury induced by various chemical substances (including drugs) and their metabolites, and is one of the main causes of acute liver injury. At present, more than 1100 marketed drugs known worldwide have potential hepatotoxicity. In China, the most common liver injury drugs are antipyretic analgesics paracetamol (APAP) and antituberculosis drugs (isoniazid, rifampicin). At present, there is a lack of specific treatment for chemical liver injury in clinical practice, and the treatment principle is to protect liver function, and prevention is the focus. Therefore, finding drugs with liver protection for the prevention and treatment of liver injury is of great significance for controlling the development of liver diseases.

[0003] Isosalicine belongs to phenolic glycosides, and is widely present in natural medicines. Its isomer salicin has the effects of anti-inflammatory, anti-tumor, anti-coagulation and anti-platelet aggregation, and becomes a natural substitute for aspirin; in the cosmetic industry, salicin is used for soothing skin irritation, reducing swelling, promoting the exfoliation of dead skin cells and inhibiting the formation of acne; in the field of food health care, salicin can also be used as a natural dietary supplement. However, the activity of isosalicine is rarely reported, and there is no report on using isosalicine as a drug for preventing and treating liver injury. SUMMARY

[0004] The application provides application of isosalicine in preparation of liver injury drugs to solve the above problems.

[0005] Specifically, the application is achieved by the following technical solutions.

[0006] The application relates to application of isosalicine (Isosalicin, hereinafter referred to as IS) in preparation of liver injury drugs, wherein the molecular formula of the isosalicine is C 13 H 18 O7, and the molecular weight is 286.28. The structural formula of the isosalicine is as follows:

[0007]

[0008] A drug for preventing and treating liver injury contains isosalicine.

[0009] Further, the liver injury drug is a drug for preventing and treating liver injury.

[0010] The medications for treating liver injury mentioned above include oral or injectable formulations. The oral formulations may be any one or more of granules, capsules, tablets, powders, pellets, and sustained-release formulations.

[0011] The IS used in this invention can be extracted from plants (such as Pedicularis macrocarpa) or chemically synthesized. The prepared drug may contain other drugs for the prevention and treatment of liver injury, as well as drug excipients or carriers. The drug can be prepared into any pharmaceutical formulation suitable for clinical use, mainly including liquid formulations, granules, tablets, powders, capsules, pellets, drop pills, sustained-release formulations, or injections. The administration methods of the formulation mainly include oral administration or injection administration.

[0012] The chemical name of IS described in this invention is isosalicylic acid (2-hydroxybenzylβ-D-glucopyranoside), with the molecular formula C. 13 H 18 O7, with a molecular weight of 286.28; scientific name Isosalicin, structural formula as follows: Figure 1 .

[0013] The beneficial effects of this invention are as follows: This invention provides for the first time the application of isosalicin in the preparation of drugs for liver injury. Isosalicin (molecular formula C...) 13 H 18 O7 (molecular weight 286.28, hereinafter referred to as IS), the drug IS did not show toxicity in the investigated concentration range (6.25-100 μM), and at the investigated concentrations of 6.25-25 μM, it could significantly improve the cell survival rate of AML-12 hepatocytes induced by acetaminophen, and had a significant hepatoprotective effect, and has good application prospects in the preparation of drugs for the prevention and treatment of liver injury. Attached Figure Description

[0014] Figure 1 It is the chemical structure of IS.

[0015] Figure 2 This is a graph showing the effect of different concentrations of IS on the survival rate of normal AML-12 hepatocytes. Data is presented in... It represents (n=3).

[0016] Figure 3 This figure shows the effect of different concentrations of IS on the survival rate of AML-12 hepatocytes induced by acetaminophen. Data are presented in... This represents (n=3). Compared with the control group, ### P<0.001; compared with the model group, **P<0.01. Detailed Implementation

[0017] The specific embodiments of the present application will be further described in detail below, but the present application is not limited to these embodiments, any improvement or replacement in the basic spirit of the present embodiments still belongs to the scope of protection claimed by the present application.

[0018] Example 1 demonstrates the toxic effect of IS on normal hepatocytes AML-12

[0019] Experimental method: CCK-8 method for detecting cell survival rate

[0020] The AML-12 cells were cultured in high glucose medium DMEM containing 10% fetal bovine serum, 100 kU / L penicillin and 100 mg / L streptomycin, 1% insulin transferrin selenium (ITS), 40 ng / mL dexamethasone (DXMS) at 37°C, 5% CO2 incubator. The AML-12 cells in logarithmic growth phase were digested with 0.25% trypsin, and then the cell density was adjusted to 3×10 4 4 / mL with medium (10% FBS + 1% double antibody + 1% ITS + 40 ng / mL DXMS), and then the cells were divided into control group (CON) and drug administration group (6.25, 12.5, 25, 50, 100 μM). Each group had 3 replicates, each well contained 100 μL cell suspension, and a blank group without cells and only with medium was set. After 24 h of culture at 37°C, 5% CO2 saturated humidity, the corresponding concentration of drug was added for a total of 24 h of incubation. Then, 10 μL CCK-8 was added to each well, and the incubation was continued for 1 h under the same culture conditions. The absorbance (A) at 450 nm of each well was determined by a microplate reader, and the cell survival rate was calculated according to the following formula:

[0021]

[0022] The experimental results Figure 2 ) can be obtained that IS has no effect on the survival rate of normal hepatocytes AML-12 at a concentration of 6.25-100 μM. This indicates that IS has no cytotoxicity on AML-12 cells at a concentration of 6.25-100 μM.

[0023] Example 2 demonstrates that IS protects normal hepatocytes from liver damage caused by acetaminophen

[0024] Experimental method: CCK-8 method for detecting cell survival rate

[0025] The culture conditions were the same as in Experiment 1. Cells were divided into a control group (CON), a model group (APAP, 10 mM), and drug-treated groups (6.25, 12.5, 25 μM). Each group had three replicates, with 100 μL of cell suspension in each well. A blank group containing only culture medium and no cells was also included. After culturing at 37℃ and 5% CO2 saturated humidity for 24 h, except for the control group, each well of the other groups was incubated with serum-free APAP culture medium at a final concentration of 10 mM for 24 h. The drug-treated groups were simultaneously incubated with the corresponding concentration of the drug. Subsequently, 10 μL of CCK-8 was added to each well, and the cells were cultured for another 1 h under the same conditions. The absorbance (A) at 450 nm was measured using a microplate reader, and cell viability was calculated using the following formula:

[0026]

[0027] Experimental results ( Figure 3 It can be concluded that IS significantly improves the survival rate of AML-12 hepatocytes induced by acetaminophen within the concentration range of 6.25–25 μM in a concentration-dependent manner. This indicates that IS has a good hepatoprotective effect and has good application prospects in the preparation of drugs for the prevention and treatment of liver injury. In summary, this invention provides for the first time the application of IS in the preparation of drugs for the prevention and treatment of liver injury.

[0028] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the equivalent meaning and scope of the claims be included within the protection scope of the present invention.

Claims

1. Use of isosyringin in the manufacture of a medicament for the prevention and treatment of liver injury caused by acetaminophen, characterized in that, The isosyringin has a molecular formula of C 13 H 18 O7; and a molecular weight of 286.28, and a specific structural formula as follows: 。

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