Application of luteolin in prevention of bone marrow type radiation sickness

By using luteolin for administration before irradiation, the problem of the lack of effective myeloid radiation sickness protection drugs in the existing technology is solved, and the effect of slowing down the damage to the hematopoietic system caused by ionizing radiation is achieved.

CN119326750APending Publication Date: 2025-01-21NANTONG UNIV +1

Patent Information

Application Number
CN202411497144.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-25
Publication Date
2025-01-21

AI Technical Summary

Technical Problem

There is a lack of effective medicines in the prior art for the prevention or treatment of bone marrow-type radiation diseases, especially in the radiation protection of the bone marrow hematopoietic system.

Method used

Luteolin is used as a pharmaceutical ingredient to prepare drugs for preventing or treating myeloid radiation sickness, and can slow down the damage to the hematopoietic system caused by ionizing radiation by administering it before irradiation.

Benefits of technology

Before irradiation, the administration can significantly slow down the hematopoietic system damage caused by ionizing radiation, manifested as the elevation of peripheral blood and slowing bone marrow damage.

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Abstract

The invention provides application of luteolin in prevention of bone marrow-type radiation sickness, relates to the technical field of biomedicine, and provides application of luteolin in preparation of drugs for prevention and treatment of bone marrow-type radiation sickness. The invention discloses an application of luteolin in prevention or treatment of bone marrow type radiation sickness and radioactive hematopoietic system injury, and finds that the hematopoietic system injury caused by ionizing radiation can be slowed down by administration of luteolin before irradiation, specifically, peripheral hemogram is increased, and bone marrow injury is slowed down.
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Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to application of luteolin in protecting against bone marrow radiation sickness. Background Art

[0002] Hematopoietic tissue is one of the most sensitive tissues to ionizing radiation. Within a certain dose range, the speed and degree of its change are positively correlated with the radiation dose received by the body. Therefore, research on protective drugs against radiation-induced damage to the hematopoietic system has great clinical and strategic significance.

[0003] Among the current radiation protection drugs, granulocyte colony stimulating factor (G-CSF), polyethylene glycol modified G-CSF (PEG-G-CSF) and recombinant granulocyte macrophage colony stimulating factor (GM-CSF) are mainly used for treatment and relief after exposure. Although amifostine can be used as a radiation prevention drug, its side effects cannot be ignored. Therefore, there is currently no good drug choice for radiation protection agents used in the bone marrow hematopoietic system. Summary of the invention

[0004] The purpose of the present invention is to solve the technical problem of the lack of radiation protection agent applied to the bone marrow hematopoietic system in the prior art.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] Application of luteolin in the preparation of drugs for preventing or treating bone marrow radiation sickness.

[0007] Preferably, the bone marrow radiation sickness refers to damage to the hematopoietic system caused by radiation.

[0008] Preferably, the bone marrow radiation sickness includes acute bone marrow radiation sickness, subacute bone marrow radiation sickness and chronic bone marrow radiation sickness.

[0009] Preferably, the radiation is gamma ray or X-ray radiation.

[0010] The present application also provides a drug for preventing or treating bone marrow radiation sickness, comprising luteolin.

[0011] Preferably, the dosage form of the drug is any one of a solvent, a solid, a suspension, a sustained-release agent or a common preparation.

[0012] Preferably, the dosage of luteolin is 10 mg / kg or 30 mg / kg.

[0013] The application of luteolin in the prevention or treatment of bone marrow radiation sickness provided in the present application has been proved through specific verification experiments that the administration of luteolin before irradiation can slow down the damage to the hematopoietic system caused by ionizing radiation, which is specifically manifested in the increase of peripheral blood count and the slowing of bone marrow damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is a bar graph comparing the cell survival rates of each group in Example 1 of the present invention;

[0015] Figure 2 The peripheral blood results of each group of mice in Example 2 of the present invention, wherein A represents the peripheral blood leukocyte count of mice, B represents the peripheral blood platelet count of mice, C represents the peripheral blood erythrocyte count of mice, D represents the peripheral blood hemoglobin count of mice, E represents the peripheral blood neutrophil count of mice, and F represents the peripheral blood lymphocyte count of mice;

[0016] Figure 3 This is a comparison chart of the bone marrow HE staining results of each group of mice in Example 2 of the present invention. DETAILED DESCRIPTION

[0017] The present invention is further described in detail below in conjunction with specific embodiments.

[0018] The use of luteolin in the preparation of drugs for preventing or treating bone marrow radiation sickness, wherein the bone marrow radiation sickness refers to damage to the hematopoietic system caused by radiation. In one embodiment, the bone marrow radiation sickness includes acute bone marrow radiation sickness, subacute bone marrow radiation sickness and chronic bone marrow radiation sickness.

[0019] The bone marrow radiation sickness refers to a disease caused by radiation that results in bone marrow damage, peripheral blood cell reduction, and decreased survival rate.

[0020] In one embodiment, the radiation is gamma radiation or X-ray radiation.

[0021] The present application also provides a drug for preventing or treating bone marrow radiation sickness, comprising luteolin, wherein the drug dosage form is any one of a solvent, a solid, a suspension, a sustained-release agent or a common preparation.

[0022] The dosage of luteolin is 10 mg / kg or 30 mg / kg.

[0023] The above contents are described below in conjunction with specific embodiments:

[0024] Example 1: In vitro experiments show that luteolin alleviates HUVEC cell death induced by X-ray irradiation

[0025] (1) Cell plating: HUVEC cells were grown to a density of about 80%, digested with trypsin, and 7,000 cells per well were plated in a 96-well plate.

[0026] (2) Cell administration: 1 h before irradiation, different concentrations of luteolin (0, 1.25, 2.5, 5, 10, 20, 40, 80 μM) were added, with 3 replicates per group.

[0027] (3) Cell irradiation: HUVEC cells were irradiated with 6 Gy (dose rate 1.0 Gy / min) of X-rays and cultured for 24 h after irradiation.

[0028] (4) Cell CCK-8 detection: The culture medium was discarded, and DMEM high-glucose culture medium containing 10% CCK-8 was added and incubated for 1 hour. The absorbance value was detected at 450 nm, and the cell survival rate was calculated and statistically analyzed.

[0029] The results are as follows Figure 1 As shown, luteolin can significantly slow down radiation-induced HUVEC cell death, indicating that luteolin can alleviate radiation-induced hematopoietic damage in vitro.

[0030] To further prove the radiation-induced hematopoietic protective effect of luteolin, we verified its protective effect in vivo through animal experiments.

[0031] Example 2: Prophylactic injection of luteolin can alleviate hematopoietic damage in mice with bone marrow radiation sickness

[0032] Specific steps: 20 C57BL / 6J male mice were randomly divided into four groups: normal control group, irradiation control group, luteolin 10 mg / kg group and luteolin 30 mg / kg group, with 5 mice in each group.

[0033] The 10 mg / kg and 30 mg / kg luteolin groups were intraperitoneally injected with corresponding doses of luteolin 3 days and 1 hour before irradiation, respectively, and the control group was injected with solvent, which was specifically 4% DMSO + 2% Tween 80 + 94% saline in volume ratio.

[0034] Then, the mice were irradiated with 6Gy (dose rate 1.0Gy / min) X-rays, and blood was collected from the tail vein of the mice 14 days after irradiation for blood cell analysis. The femurs of the mice were routinely fixed, dehydrated, paraffin-embedded, sectioned, and HE-stained.

[0035] Peripheral blood test results Figure 2As shown in the results, radiation exposure significantly reduced the amount of white blood cells, platelets, red blood cells, hemoglobin, neutrophils and lymphocyte ratio in the peripheral blood of mice, while the values ​​of the luteolin group increased significantly, and the difference was statistically significant. This shows that luteolin can significantly alleviate the damage to the hematopoietic system caused by ionizing radiation and reduce the symptoms of bone marrow radiation sickness.

[0036] Bone marrow HE staining results Figure 3 As shown in the figure, compared with the normal control group, the bone marrow cavity of the irradiated control group was significantly empty, the number of bone marrow nucleated cells decreased sharply, and the number of cavities increased. Injection of luteolin can increase the number of bone marrow nucleated cells, reduce the number of cavities in the bone marrow cavity, and reduce bone marrow damage. This shows that luteolin significantly improves bone marrow damage caused by ionizing radiation.

[0037] In summary, the application of luteolin in the prevention or treatment of bone marrow radiation sickness provided in this application has been proved through specific verification experiments that the administration of luteolin before irradiation can slow down the damage to the hematopoietic system caused by ionizing radiation, which is specifically manifested in increasing peripheral blood count and slowing down bone marrow damage.

Claims

1. Application of luteolin in the preparation of drugs for preventing or treating bone marrow radiation sickness.

2. The use of luteolin according to claim 1 in the preparation of a drug for preventing or treating bone marrow radiation sickness, characterized in that: The bone marrow radiation sickness refers to the damage to the hematopoietic system caused by radiation.

3. The use of luteolin according to claim 2 in the preparation of a drug for preventing or treating bone marrow radiation sickness, characterized in that: The bone marrow radiation sickness includes acute bone marrow radiation sickness, subacute bone marrow radiation sickness and chronic bone marrow radiation sickness.

4. The use of luteolin in the preparation of a drug for preventing or treating bone marrow radiation sickness according to claim 1, characterized in that: The radiation refers to gamma rays or X-ray radiation.

5. A drug for preventing or treating bone marrow radiation sickness, characterized in that: Including luteolin.

6. The drug for preventing or treating bone marrow radiation sickness according to claim 5, characterized in that: The dosage form of the drug is any one of solvent, solid, suspension, sustained-release agent or common preparation.

7. The drug for preventing or treating bone marrow radiation sickness according to claim 5, characterized in that: The dosage of luteolin is 10 mg / kg or 30 mg / kg.

Citation Information

Patent Citations

  • Novel compounds with radioprotective effects and preparation method and pharmaceutical use thereof

    CN107021961A

  • Application of luteolin to preparation of medicine for treating oxidative stress injury of testicular tissue

    CN107198684A

  • Application of luteolin in preventing radiation damage and preparing medicine for preventing radiation damage

    CN117679407A

  • Compositions and methods for treating or preventing radiation injury

    US20120029071A1

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