Application of mogroside V in acetaminophen-induced liver injury

Abstract

The invention relates to application of mogroside V in acetaminophen-induced liver injury, in particular to application of mogroside V in preparation of drugs for treating or preventing acetaminophen-induced liver injury. Research finds that mogroside V can obviously inhibit acetaminophen-induced liver injury, including reduction of liver necrosis area, reduction of serum glutamic-pyruvic transaminase and glutamic oxalacetic transaminase activity, and reduction of macrophage cell and inflammatory cell infiltration. Therefore, the ingestion of mogroside V is a medicine for effectively treating or preventing liver injury caused by excessive taking of acetaminophen.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to application of mogroside V in acetaminophen-induced liver damage. Background Art

[0002] Acetaminophen (APAP) is one of the most common cold medicines, but its overdose can cause severe liver damage or even liver failure. Currently, the only drug for treating acetaminophen-induced liver damage is N-acetylcysteine, but its effective time window is narrow and is only effective within 8 hours of overdose.

[0003] Monk fruit is the fruit of the plant Momordica grosvenori of the Cucurbitaceae family and is a famous Chinese medicinal material for both medicine and food. Mogroside is a unique chemical component of Momordica grosvenori, among which Mogroside V has the highest content; it has been proven that Momordica grosvenori has the pharmacological effects of clearing away heat and detoxification, relieving sore throat and reducing phlegm, and antibacterial and anti-inflammatory.

[0004] In view of this, the present invention provides the use of mogroside V in acetaminophen-induced liver injury. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide application of mogroside V in acetaminophen-induced liver damage.

[0006] The technical solution of the present invention to solve the above technical problems is as follows:

[0007] Firstly, the use of mogroside V in the preparation of a drug for treating or preventing acetaminophen-induced liver injury.

[0008] Mogroside V (MV) is an extract of Momordica grosvenori and a Chinese medicine monomer. Its molecular formula is C 60 H 102 O 29 , the structural formula is as follows:

[0009] Furthermore, the mogroside V treats acetaminophen-induced liver damage by reducing the area of ​​liver necrosis caused by acetaminophen.

[0010] Furthermore, the mogroside V treats acetaminophen-induced liver damage by reducing the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by acetaminophen.

[0011] Furthermore, the mogroside V treats acetaminophen-induced liver injury by reducing the increase of macrophages in the liver necrosis area caused by acetaminophen.

[0012] Furthermore, the mogroside V treats acetaminophen-induced liver injury by reducing the increase of S100A9-positive inflammatory cells in the liver necrosis area caused by acetaminophen.

[0013] In a second aspect, a drug for treating acetaminophen-induced liver damage comprises mogroside V.

[0014] The actual dosage of the active ingredient (mogroside V of the present invention) in the drug should be determined according to a variety of relevant factors, including the severity of the disease to be treated, the route of administration, the patient's age, gender, and weight. Therefore, the above dosage should not limit the scope of protection of the present invention in any way.

[0015] Furthermore, pharmaceutically acceptable excipients are also included.

[0016] Furthermore, the auxiliary materials include any one of lubricants, fillers, binders, disintegrants, solubilizers, and stabilizers, or a combination of at least two of them.

[0017] Furthermore, a pharmaceutically acceptable carrier is also included.

[0018] Furthermore, the dosage form of the drug is tablets, capsules, pills, granules, syrups, suspensions, creams or ointments.

[0019] The drug may be in any pharmaceutically acceptable dosage form. The suitable dosage of the drug may be prescribed in a variety of ways depending on factors such as the formulation method, administration method, patient's age, weight, sex, morbidity, diet, administration time, administration route, and reaction sensitivity. A skilled doctor can usually easily determine the prescription and the dosage that is effective for the desired treatment.

[0020] The beneficial effects of the present invention are as follows: the present invention has found that mogroside V can significantly inhibit liver damage induced by acetaminophen, including: reducing the area of ​​liver necrosis, reducing serum alanine aminotransferase and aspartate aminotransferase activities, and reducing macrophage and inflammatory cell infiltration. Therefore, taking mogroside V is an effective drug for preventing liver damage caused by excessive acetaminophen. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a picture of liver necrosis area detected by HE staining of the present invention;

[0022] Figure 2 This is a statistical diagram of the area of ​​liver necrosis detected by HE staining of the present invention;

[0023] Figure 3 The results of the ALT and AST activity tests of the present invention are shown in the figure below. The left figure shows the ALT activity results, and the right figure shows the AST activity results.

[0024] Figure 4 This is a graph showing the number of CD68 positive macrophages detected by immunohistochemistry of the present invention;

[0025] Figure 5 This is a statistical result diagram of the number of CD68 positive macrophages detected by immunohistochemistry of the present invention;

[0026] Figure 6 This is a graph showing the number of S100A9 positive inflammatory cells detected by immunohistochemistry of the present invention;

[0027] Figure 7 This is a statistical result diagram of the number of S100A9 positive inflammatory cells detected by immunohistochemistry of the present invention. DETAILED DESCRIPTION

[0028] The principles and features of the present invention are described below, and the examples are only used to explain the present invention and are not used to limit the scope of the present invention. If no specific technology or conditions are specified in the embodiments, the technology or conditions described in the literature in this field or the product instructions are used. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased through regular channels.

[0029] Sources of materials and reagents:

[0030] In the following examples, mogroside V is abbreviated as MV and is sourced from Solebao Company; acetaminophen is abbreviated as APAP and is sourced from MedChemExpress; and C57 mice are sourced from Jiangsu Huachuang Xinnuo Pharmaceutical Technology Co., Ltd.

[0031] Example 1: Mogroside V can reduce the area of ​​liver necrosis caused by APAP.

[0032] 21-23g C57 mice were fasted for 15 hours and divided into three groups, with 6 mice in each group: (1) control mice, intraperitoneal injection of normal saline; (2) APAP group, intraperitoneal injection of normal saline first, and APAP (300mg / kg) intraperitoneal injection 1 hour later; (3) MV+APAP group, intraperitoneal injection of MV (10mg / kg mouse) first, and APAP (300mg / kg) intraperitoneal injection 1 hour later. After 24 hours, the mouse livers were taken and the area of ​​liver necrosis was detected by HE staining. The results showed that APAP can cause liver necrosis, but MV can significantly reduce the area of ​​liver necrosis ( Figure 1 and 2 ).

[0033] Example 2: Mogroside V can reduce the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice induced by APAP.

[0034] 21-23g C57 mice were fasted for 15 hours and divided into three groups, with 6 mice in each group: (1) control mice, intraperitoneal injection of normal saline; (2) APAP group, intraperitoneal injection of normal saline first, and APAP (300mg / kg) intraperitoneal injection 1h later; (3) MV+APAP group, intraperitoneal injection of MV (10mg / kg mouse) first, and APAP (300mg / kg) intraperitoneal injection 1h later. After 24 hours, the mouse serum was collected to detect ALT and AST activities. The results showed that APAP could lead to increased serum ALT and AST levels, but MV could significantly reduce the increase in both levels ( Figure 3 ).

[0035] Example 3: Mogroside V can reduce the increase of macrophages in the liver necrosis area of ​​mice induced by APAP.

[0036] 21-23g C57 mice were fasted for 15 hours and divided into three groups, with 6 mice in each group: (1) control mice, intraperitoneal injection of normal saline; (2) APAP group, intraperitoneal injection of normal saline first, and APAP (300mg / kg) intraperitoneal injection 1h later; (3) MV+APAP group, intraperitoneal injection of MV (10mg / kg mouse) first, and APAP (300mg / kg) intraperitoneal injection 1h later. 24 hours later, the mouse livers were obtained and the number of CD68-positive macrophages was detected by immunohistochemistry. The results showed that APAP could cause a significant increase in the number of CD68-positive macrophages in the necrotic area of ​​the liver, but MV could significantly reduce the number of CD68-positive macrophages in the necrotic area ( Figure 4 and 5 ).

[0037] Example 4: Mogroside V can reduce the increase of S100A9-positive inflammatory cells in the liver necrosis area of ​​mice induced by APAP.

[0038] 21-23g C57 mice were fasted for 15 hours and divided into three groups, with 6 mice in each group: (1) control mice, intraperitoneal injection of normal saline; (2) APAP group, intraperitoneal injection of normal saline first, and APAP (300mg / kg) intraperitoneal injection 1h later; (3) MV+APAP group, intraperitoneal injection of MV (10mg / kg mouse) first, and APAP (300mg / kg) intraperitoneal injection 1h later. After 24 hours, the mouse livers were obtained and the number of S100A9-positive inflammatory cells was detected by immunohistochemistry. The results showed that APAP could cause a significant increase in the number of S100A9-positive inflammatory cells in the necrotic area of ​​the liver, but MV could significantly reduce the number of S100A9-positive inflammatory cells in the necrotic area ( Figure 6 and 7 ).

[0039] In summary, mogroside V can significantly inhibit acetaminophen-induced liver damage, including reducing the area of ​​liver necrosis, reducing serum alanine aminotransferase and aspartate aminotransferase activities, and reducing macrophage and inflammatory cell infiltration. Therefore, taking mogroside V is an effective drug to prevent liver damage caused by acetaminophen overdose.

[0040] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. Application of mogroside V in the preparation of drugs for treating or preventing acetaminophen-induced liver injury.

2. The use according to claim 1, characterized in that: The mogroside V treats acetaminophen-induced liver damage by reducing the area of ​​liver necrosis caused by acetaminophen.

3. The use according to claim 1, characterized in that: The mogroside V treats acetaminophen-induced liver damage by reducing the serum alanine aminotransferase and aspartate aminotransferase levels caused by acetaminophen.

4. The use according to claim 1, characterized in that: The mogroside V treats acetaminophen-induced liver injury by reducing the increase of macrophages in the liver necrosis area caused by acetaminophen.

5. The use according to claim 1, characterized in that: The mogroside V treats acetaminophen-induced liver injury by reducing the increase of S100A9-positive inflammatory cells in the liver necrosis area caused by acetaminophen.

6. A drug for treating acetaminophen-induced liver damage, characterized in that: The medicine includes mogroside V.

7. A drug for treating acetaminophen-induced liver damage according to claim 6, characterized in that: Pharmaceutically acceptable excipients are also included.

8. A drug for treating acetaminophen-induced liver damage according to claim 7, characterized in that: The auxiliary materials include any one of lubricants, fillers, binders, disintegrants, solubilizers, and stabilizers, or a combination of at least two of them.

9. A drug for treating acetaminophen-induced liver damage according to claim 6, characterized in that: Also included are pharmaceutically acceptable carriers.

10. A drug for treating acetaminophen-induced liver damage according to claim 6, characterized in that: The dosage form of the medicine is tablet, capsule, pill, granule, syrup, suspension, cream or ointment.

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