Application of evodiamine in preparation of anti-osteoporosis drug and anti-osteoporosis drug

An anti-osteoporosis and evodiamine technology, applied in the field of biomedicine, can solve problems such as adverse reactions and increased risk of breast cancer, and achieve the effects of inhibiting bone resorption, alleviating adverse reactions, and promoting bone formation.

Inactive Publication Date: 2018-01-12
CHINA ACAD OF SCI NORTHWEST HIGHLAND BIOLOGY INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, studies have found that hormone replacement therapy increases the risk of breast cancer in women, and phosphate preparations that inhibit bone resorption have relatively large adverse reactions in clinical applications

Method used

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  • Application of evodiamine in preparation of anti-osteoporosis drug and anti-osteoporosis drug
  • Application of evodiamine in preparation of anti-osteoporosis drug and anti-osteoporosis drug
  • Application of evodiamine in preparation of anti-osteoporosis drug and anti-osteoporosis drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1 evodiamine ( figure 1 ) toxicity to mouse bone marrow macrophages

[0048] In order to show that the inhibitory effect of evodiamine on osteoclast differentiation of the present invention is not caused by the cytotoxicity of evodiamine, the MTT test is carried out on mouse bone marrow macrophages with evodiamine, and the apoptosis of cells is tested by flow cytometry. Mortality.

[0049] 1. MTT test (thiazolium blue colorimetric method):

[0050] Mouse bone marrow macrophages were cultured using conventional experimental methods, and then the mouse bone marrow macrophages were cultured at 1×10 4 Each cell / cell was seeded in a 96-well plate, and the medium was discarded after the cells were overgrown, and evodiamine was added to each fresh medium at a final concentration of 0 (Control), 10 μg / mL, 20 μg / mL and 30 μg / mL, respectively. Then add to the 96-well plate, then, use the MTT assay method to evaluate the inhibitory effect of evodiamine on the prolife...

Embodiment 2

[0053] Example 2 Evodiamine can inhibit the differentiation of hematopoietic stem cells into osteoclasts

[0054] According to research findings, mouse bone marrow macrophages can differentiate into osteoclasts under the stimulation of nuclear factor receptor activator ligand RANKL and human macrophage colony-stimulating factor. Osteoporosis is often caused by excessive bone resorption as a result of overactivation of osteoclasts.

[0055] Therefore, mouse bone marrow macrophages are selected as the cell model to study the effect of evodiamine on RANKL-induced osteoclastogenesis is very suitable. To observe whether evodiamine can inhibit the expression of specific genes related to osteoclasts and its effect on the osteophagy ability of osteoclasts, so as to illustrate the application and mechanism of evodiamine in the preparation of drugs for preventing and treating osteoporosis.

[0056] In order to show that evodiamine of the present invention can inhibit the differentiatio...

Embodiment 3

[0059] Example 3 Evodiamine can inhibit the expression of osteoclast formation transcription factors

[0060] In order to show that evodiamine can effectively inhibit the expression of transcription factors c-FOS and NFATc1 in osteoclast formation, mouse bone marrow macrophages were injected at 1×10 4 Each cell / cell was seeded in a 96-well plate, and the medium was discarded after the cells were overgrown, and evodiamine with a final concentration of 0 μg / mL, 5 μg / mL, 10 μg / mL and 15 μg / mL was added to each fresh medium, and then Added to the 96-well plate, while RANKL (75ng / mL) induced mouse bone marrow macrophages to differentiate into osteoclasts. Subsequently, the expression of the transcription factors c-FOS and NFATc1 of osteoclast formation was analyzed by electrophoresis ( Figure 8 ), GAPDH (glyceraldehyde-3-phosphate dehydrogenase) was used as a control group. Experiments showed that with the increase of evodiamine concentration, its inhibitory effect on the expres...

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Abstract

The invention provides application of evodiamine in preparation of an anti-osteoporosis drug and the anti-osteoporosis drug and relates to the technical field of biological medicine. The evodiamine can inhibit activation of protein kinase in an RANKL-induced osteoclast differentiation and maturation RANKL-ERK-NFAT signal channel in effective dose, further bone phagocytosis capability of RANKL-induced osteoclast is inhibited, expression of osteoclast differentiation specific genes such as c-Fos and NFATc1 is obviously reduced, bone absorption is inhibited, bone formation is promoted, and finally the effect of preventing osteoporosis is achieved. The application of the evodiamine in preparation of the anti-osteoporosis drug has the characteristics of definite curative effect and small side effect, and the problem that an existing medicine used for treating bone loss disease has serious adverse reaction in clinical application is relieved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of evodiamine in the preparation of anti-osteoporosis medicine and the medicine thereof. Background technique [0002] Osteoclasts are a kind of bone tissue components and are the only cells with bone resorption function in the human body. Excessive production of osteoclasts leads to enhanced bone resorption, which in turn causes osteoporosis, rheumatoid arthritis, Prosthetic aseptic looseness, multiple myeloma and metastatic bone tumors and other diseases, therefore, the research on osteoclasts is the key to the treatment of the above diseases including osteoporosis. [0003] Existing studies have found that osteoclasts originate from bone marrow mononuclear-macrophage lineage cells, and must rely on some incentives to induce differentiation and development into multinucleated mature osteoclasts in vivo, and finally be activated. At present, it is believed t...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61P19/10
Inventor 江磊陶燕铎邵赟
Owner CHINA ACAD OF SCI NORTHWEST HIGHLAND BIOLOGY INST
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