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Use of 23-hydroxy betulic acid in inhibiting blood vessel formation

An angiogenesis and betulinic acid technology, applied in cardiovascular system diseases, organic active ingredients, non-central analgesics, etc., can solve the problems of unclear anti-cancer mechanism and limited anti-cancer effect, and achieve drug resistance, The effect of high efficacy and small dose

Inactive Publication Date: 2005-10-19
JIANGSU INST OF NUCLEAR MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the unclear mechanism of its anticancer action, its anticancer effect is limited.

Method used

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  • Use of 23-hydroxy betulic acid in inhibiting blood vessel formation
  • Use of 23-hydroxy betulic acid in inhibiting blood vessel formation
  • Use of 23-hydroxy betulic acid in inhibiting blood vessel formation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1: The inhibitory effect of 23-hydroxybetulinic acid on the proliferation of human vascular endothelial cells.

[0018] 1.1 In vitro proliferation test of 23-hydroxybetulinic acid (23-HBA) on human vascular endothelial cells (HMEC)

[0019] Place human vascular endothelial cells (HMEC, a gift from the French National Institutes of Health and Medical Research) in MCDB containing 1 mmol-glutamine, 1 μg / mL hydrocortisone, 10 ng / mL epidermal growth factor (EGF) and 15% calf serum Cultured in -131 medium (37°C, 5% CO 2 , 95% humidity). Take the cells in the logarithmic growth phase, and take 10 5 cell / mL cells were seeded in a 96-well plate, 100 μL / well, with 4 parallel wells for each group, and placed at 37°C, 5% humidified CO 2 incubator overnight. Add 23-HBA at different concentrations (10-100 μg / mL), and use the solvent dimethyl sulfoxide (DMSO) as a negative control. After culturing for 48 hours, remove the supernatant, and gently add 100 μL of 10% trichloro...

Embodiment 2

[0024] Example 2: Inhibitory effect of 23-hydroxybetulinic acid on tube formation ability of human vascular endothelial cells.

[0025] 2.1 In vitro tubule formation test

[0026] Add 50 μL growth-reduced Matrigel to the bottom of the 96-well culture plate at 4°C, and incubate in the incubator at 37°C for 4 hours after paving, mix 23-HBA with 15% calf serum MCDB-131 culture medium and HMEC cells (4×10 4 cells / well, the volume of each well is 0.25ml) and then added to the culture plate after mixing. The final concentration of 23-HBA is 1-60 μg / mL, and the vehicle is used as a negative control. 37°C, 5% humidified CO 2After culturing for 24 hours, use an inverted microscope to observe the effect of 23-HBA on the construction of blood vessels by endothelial cells in vitro. The results showed that 23-HBA significantly inhibited the formation of Matrigel tubules in HMEC cells in vitro. When the concentration of 23-HBA is 1 μg / mL, it has a significant effect on the tubule formati...

Embodiment 3

[0031] Example 3: Inhibitory effect of 23-hydroxybetulinic acid on the migration ability of human vascular endothelial cells.

[0032] 3.1 Inhibition of vascular endothelial cell migration test

[0033] Tilt the 24-well plate at 60°, add 1% agarose to the bottom 1 / 2 of each well, wash it with medium after solidification, add HMEC cells to the side without agarose, 10 per well 5 cells. After the cells adhered to the wall, negative control and 23-HBA of different concentrations (1-60 μg / ml) were added, and the number of endothelial cells migrating to the other half of each group was recorded with an inverted microscope after 72 hours. The results showed that the number of cells migrating in the group without 23-HBA intervention was higher, and the inhibition rate of cell migration was concentration-dependent. 23-HBA may inhibit the formation of new blood vessels by inhibiting the migration of vascular endothelial cells (Table 2).

[0034] Drug concentration (μg / mL)

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Abstract

The present invention relates to the application of 23-hyroxy betulic acid in inhibiting vascularization, and relates to Chinese medicine application technology. The present invention discloses the new use of 23-hyroxy betulic acid in inhibiting vascularization, and research shows that 23-hyroxy betulic acid has vascularization inhibiting effect. The effective dosage of 23-hyroxy betulic acid in preventing and treating medicine for inhibiting vascularization is 3-50 mg each kg of body weight each day. The present invention adopts vascularization as disease treating target, and has the advantages of specificity; direct action of medicine to blood vessel endothelial cell resulting in small dosage, high curative effect and less side effect; and less drug resistance.

Description

technical field [0001] The application of 23-hydroxy betulinic acid in inhibiting angiogenesis relates to the technical field of application of traditional Chinese medicines, especially the new application of 23-hydroxy betulinic acid. Background technique [0002] The growth and metastasis of primary tumors depend on the generation of new blood vessels from pre-existing blood vessels, a process called angiogenesis. Tumors can not only obtain nutrients and oxygen from the host through tumor blood vessels, but also continuously transport metastatic cells to the host through tumor blood vessels, and continue to grow and induce blood vessel formation in other parts of the body, leading to tumor metastasis. If there is no angiogenesis, the growth of the primary tumor will not exceed 1-2mm, and there will be no invasion and metastasis. Inhibiting tumor angiogenesis is closely related to blocking tumor occurrence, development, invasion and metastasis, and can prevent the malignan...

Claims

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Application Information

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IPC IPC(8): A61K31/56A61P9/10A61P17/06A61P19/02A61P27/02A61P29/00A61P35/00
Inventor 杨敏蒋孟军张荣军周尧远曹国宪项景德王广基叶文才
Owner JIANGSU INST OF NUCLEAR MEDICINE
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