CN111012815A

CN111012815A - Application of bighead atractylodes rhizome volatile oil in preparation of medicine for treating acute liver injury

Info

Publication number: CN111012815A
Application number: CN202010004902.8A
Authority: CN
Inventors: 冯海华; 李铮; 王建锋; 赵立磊; 邓旭明; 徐蕾; 邱家章
Original assignee: Jilin University
Current assignee: Jilin University
Priority date: 2020-01-03
Filing date: 2020-01-03
Publication date: 2020-04-17

Abstract

The invention provides application of bighead atractylodes rhizome volatile oil in preparation of a medicine for treating acute liver injury, and experiments on mice acute liver injury by the bighead atractylodes rhizome volatile oil prove that the bighead atractylodes rhizome volatile oil has a better treatment effect on mice acute liver injury caused by acetaminophen. The invention uses the bighead atractylodes rhizome volatile oil to protect mice acute liver injury caused by acetaminophen, has no obvious toxic effect in a test, and has higher cure rate. Therefore, the bighead atractylodes rhizome volatile oil can be used for developing new medicaments and has important significance for confirming medicament targets.

Description

Application of bighead atractylodes rhizome volatile oil in preparation of medicine for treating acute liver injury

Technical Field

The invention relates to application of bighead atractylodes rhizome volatile oil in preparation of a medicine for treating acute liver injury, and belongs to the field of medicines.

Background

The bighead atractylodes rhizome is a common and important bulk Chinese medicinal material and has the functions of tonifying spleen and strengthening stomach, eliminating dampness and promoting diuresis, stopping sweating and preventing miscarriage and the like. The rhizome of Atractylodes macrocephala contains volatile oil, the main components of the oil are atractylone, atractylol, atractylenolide, etc., and the drug has certain curative effect on ascites due to cirrhosis, primary liver cancer, Meniere's syndrome, chronic lumbago, acute enteritis, leukopenia, etc. At present, no report related to preparation of Nrf2 activator of bighead atractylodes rhizome volatile oil is found.

The liver is an important organ of drug metabolism. Most drugs or their active metabolites accumulate in the liver and are easily damaged. Thus, liver damage is one of the most common adverse drug reactions. With the continuous update of clinical drugs and the application of multiple drug combinations, Drug Induced Liver Injury (DILI) has become the most common cause of acute liver injury. Acute liver injury can lead to liver failure and even life-threatening. In mainland china, the incidence of disease is in every one hundred thousand people and is on an increasing trend. This phenomenon may be associated with different regions, ethnicities, population bases, drug classes, unregulated use of drugs, and dietary supplements. Oxidative stress plays an important role in the mechanisms of liver disease. It accelerates the development and progression of liver damage. Almost all liver damage patterns are associated with increased oxidative stress and antioxidant defense systems. Since activation of Nrf2 is associated with enhancement of the endogenous antioxidant system, it may be an ideal target for reducing oxidative stress. The simultaneous use of a natural Nrf2 activator with other pharmacological agents may be a potential method of reducing liver damage. Potential drug candidates include crude herb extracts as well as purified phytochemicals.

Disclosure of Invention

The invention discovers that the volatile oil of the largehead atractylodes rhizome protects the liver injury caused by acute liver injury

The invention discovers that the bighead atractylodes rhizome volatile oil has better treatment effect on mice acute liver injury caused by acetaminophen

The application of the preferred rhizoma atractylodis macrocephalae volatile oil in preparing the medicine for treating acute liver injury in the technical scheme of the invention

The invention can prepare the bighead atractylodes rhizome volatile oil and pharmaceutically acceptable auxiliary materials into various dosage forms

The invention preferably prepares the bighead atractylodes rhizome volatile oil into the dosage forms of injection, capsule and the like

Drawings

FIG. 1 is a graph showing the results of HE staining of mouse livers according to the present invention;

wherein, panel A is blank control group, panel B is model group, panel C is drug control group, and panels D-F are drug treatment group (100mg/kg, 200mg/kg, 300mg/kg)

FIG. 2 is a graph showing the results of AST and ALT measurement in blood of mice of the present invention;

FIG. 3 is a graph showing the results of the expression of the protein for nuclear transport of Nrf2 in the liver of a mouse according to the present invention.

Detailed Description

The present invention is further illustrated by the following examples, which do not limit the present invention in any way, and any modifications or changes that can be easily made by a person skilled in the art to the present invention will fall within the scope of the claims of the present invention without departing from the technical solution of the present invention.

Experimental and therapeutic study on acute liver injury of mice

1. Establishment of mouse acute liver injury model

A male C57BL/6 mouse weighing 18-20g is injected with 200 mu L (500mg/kg) of acetaminophen solution by the abdominal cavity to establish a mouse acute liver injury model.

2. Pathology experiment

C57BL/6 mice with the same body condition were randomly assigned. Administering 200 μ L of Atractylodis rhizoma volatile oil (100mg/kg, 200mg/kg, 300mg/kg) with different concentrations to the drug group by intragastric administration one hour before acetaminophen injection; the model control group was administered 200 μ L of saline solution by gavage at the same time point; the drug control group was also administered 200. mu.L of Atractylodis rhizoma volatile oil (300mg/kg) by gavage at the same time point. After the administration according to the administration scheme, the liver is taken after 6 hours to prepare pathological sections, and the protective effect of the drug on acute liver injury is observed. The results are shown in FIG. 1.

3. Glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase experiments

C57BL/6 mice with the same body condition were randomly assigned. Administering 200 μ L of Atractylodis rhizoma volatile oil (100mg/kg, 200mg/kg, 300mg/kg) with different concentrations to the drug group by intragastric administration one hour before acetaminophen injection; the model control group was administered 200 μ L of saline solution by gavage at the same time point; the drug control group was also administered 200. mu.L of Atractylodis rhizoma volatile oil (300mg/kg) by gavage at the same time point. After the administration of the drug according to the dosing schedule, blood was taken 6 hours later, and the levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were measured. After drug administration, the levels of AST and ALT in the blood were significantly reduced compared to the model group. The results are shown in FIG. 2.

Nrf2 pathway experiments

C57BL/6 mice with the same body condition were randomly assigned. Administering 200 μ L of Atractylodis rhizoma volatile oil (100mg/kg, 200mg/kg, 300mg/kg) with different concentrations to the drug group by intragastric administration one hour before acetaminophen injection; the model control group was administered 200 μ L of saline solution by gavage at the same time point; the drug control group was also administered 200. mu.L of Atractylodis rhizoma volatile oil (300mg/kg) by gavage at the same time point. After dosing according to the dosing schedule, the mouse livers were taken 6 hours later and subjected to western blot experiments. (see FIG. 3 for results). After the protection of the bighead atractylodes rhizome volatile oil, the level of Nrf2 nuclear transport in the liver of a mouse is obviously increased.

5. Test of protective rate

C57BL/6 mice with the same body condition were randomly assigned. Administering 200 μ L of Atractylodis rhizoma volatile oil (300mg/kg) to the medicinal group via intragastric administration one hour before the injection of acetaminophen; the model control group was given 200 μ L of saline solution by gavage at the same time point. 200 μ L of Atractylodis rhizoma volatile oil (300mg/kg) was administered via gavage at the same time point as drug control group. After dosing according to the dosing schedule, the mortality of the mice was recorded over 6, 12, 24 hours, respectively. There were no dead mice within 24 hours in the drug control group and the model control group, and the model group and the drug-treated group are recorded in the table.

TABLE 3 Largehead Atractylodes rhizome volatile oil reduces mortality of mouse acute liver injury caused by acetaminophen

Claims

1. Application of Atractylodis rhizoma volatile oil in preparing medicine for protecting liver injury caused by acute liver injury is provided.

2. The use of claim 1, wherein the acute liver injury is acute liver injury caused by acetaminophen, and wherein the liver injury is acute liver injury caused by acetaminophen.

3. The use as claimed in claim 1, wherein the said medicament is pharmaceutically acceptable carrier, such as injection, capsule, etc.