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Application of lobelia alkaloids in the preparation of anti-angiogenic disease drugs

An anti-angiogenesis and angiogenesis technology, applied in the field of medicine, can solve problems such as cytotoxicity, and achieve the effect of inhibiting proliferation and angiogenesis

Active Publication Date: 2018-06-29
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Japanese scholars have found that polyacetylene components have significant cytotoxicity to tumor cells, but so far there has been no report on the inhibition of angiogenesis by lobelia alkaloids, or the study of stabilizing AS plaques by inhibiting angiogenesis

Method used

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  • Application of lobelia alkaloids in the preparation of anti-angiogenic disease drugs
  • Application of lobelia alkaloids in the preparation of anti-angiogenic disease drugs
  • Application of lobelia alkaloids in the preparation of anti-angiogenic disease drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1: the preparation of lobelia alkaloid

[0031] Lobelia traditional Chinese medicine (whole herb with root) is produced in Guangdong Province and purchased from Jinan Jianlian Pharmaceutical Company. This example extracts lobelia alkaloids for experimental research.

[0032] The gauze bag that fills lobelia 3kg is put into extractor, adds 95% ethanol, makes it submerge gauze bag 3cm. Put it in a closed extractor and heat it for 2 hours to make the drug components enter into ethanol to become drug alcohol extract. Heat the drug alcohol extract in the vacuum concentration unit for 2 hours to evaporate the ethanol and concentrate the drug solution. The gaseous ethanol is converted into a liquid state through a low-temperature pipeline and recovered for reuse. The extraction is repeated 3 times. The lobelia extract was placed in a rotary evaporator and heated for 20 minutes to concentrate it into a paste. Add 3% HCl to acidify and dissolve until the pH value i...

Embodiment 2

[0034] Example 2: Effects of lobelia alkaloids on blood lipids and body weight of apoE- / - mice fed with high fat

[0035] 1. Experimental animals: apoE- / - mice fed with high fat

[0036] 2. Materials and samples: The LCLA extracted in Example 1 was first dissolved in DMSO, and then dissolved in PBS to form the corresponding low, medium and high dose groups, which are ready-to-use.

[0037] 3. Experimental method:

[0038] (1) Experimental grouping: ApoE- / - mice were given a high-fat diet and randomly divided into the following groups:

[0039] ①PBS group: PBS 0.5mL was fed by gastric tube every day;

[0040] ②Lobelia alkaloid high-dose group: LCLA 40mg / kg was administered by gastric tube every day;

[0041] ③Lobelia alkaloid medium dose group: LCLA 20mg / kg was administered by gastric tube every day;

[0042] ④Lobelia alkaloid low-dose group: LCLA 10mg / kg per day by gastric tube;

[0043] ⑤Simvastatin group: Simvastatin 50mg / kg was administered by gastric tube every day;

...

Embodiment 3

[0051] Example 3: Effects of lobelia alkaloids on the stability of aortic root plaques in apoE- / - mice fed with high fat

[0052] 1. Experimental animals and experimental groups are the same as in Example 2.

[0053] 2. Experimental method: After 12 weeks of administration, the mice were killed, the chest cavity was quickly opened, the left ventricle was retrogradely perfused with liquid to the aorta, the aorta was bluntly separated, and the root of the aorta was fixed in paraformaldehyde soaking solution for pathological specimens , and the rest of the aorta were preserved at -80°, pending molecular biology testing.

[0054] (1) HE staining: After the aortic root was fixed, the paraformaldehyde was washed away with running water, embedded with OCT, sectioned, and HE stained to observe the shape and size of the plaque, the integrity of the fibrous cap, and the fracture of the elastic fibers of the basement membrane.

[0055] (2) Other special staining: Select adjacent section...

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Abstract

The invention relates to the application of lobelia alkaloids in the preparation of anti-angiogenesis disease drugs. The results of in vivo and in vitro experiments of the present invention show that lobelia alkaloids can inhibit angiogenesis in atherosclerotic plaques to stabilize plaques, can significantly inhibit zebrafish angiogenesis, and can inhibit the proliferation, migration and in vitro formation of vascular endothelial cells. loop, its mechanism may be related to p38MAPK protein. The experimental results show that lobelia alkaloids have anti-angiogenic activity and can be used as an angiogenesis inhibitor, which provides a new therapeutic method for the clinical prevention and treatment of atherosclerotic plaque rupture and other related diseases, and can also be applied to the preparation of tumors, Drugs for angiogenesis-dependent and angiogenesis-related diseases such as arthritis, skin and eye diseases, vascular dementia, and endometriosis.

Description

technical field [0001] The invention relates to the application of lobelia alkaloids in the preparation of anti-angiogenesis disease drugs, belonging to the technical field of medicine. Background technique [0002] Coronary heart disease and stroke caused by atherosclerosis (AS) plaque rupture have surpassed cancer and become the disease with the highest mortality rate in China. Studies have found that angiogenesis in AS plaques is an important factor in determining plaque growth, vulnerability, and rupture. The intima of the blood vessel with atherosclerotic plaque becomes thicker and the distance increases, resulting in local ischemia and hypoxia. Intraplaque angiogenesis stimulates the exudation of inflammatory cells and the expression of adhesion molecules, and is prone to rupture and bleeding, increasing plaque instability. "Angiogenesis" is the process of generating new blood vessels on the basis of the original vascular structure, that is, vascular endothelial cell...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K36/34A61P9/10A61P35/00A61P19/02A61P17/00A61P27/02A61P25/28A61P15/00
CPCA61K36/34A61K2236/333A61K2236/51A61K2236/55
Inventor 王婧婧刘尚明杜占慧张文程
Owner SHANDONG UNIV
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