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Application of saponin compounds capable of reducing PCSK9 secreted by hepatocytes in gynostemma pentaphyllum total glycoside particles

A compound and hepatocyte technology, applied in the field of natural medicinal chemistry, can solve the problems of increasing PCSK9 and reducing lipid-lowering activity, and achieve the effect of enhancing lipid-lowering effect, blood-lipid-lowering activity and drug safety guarantee.

Pending Publication Date: 2022-07-15
湖南华宝通制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In order to solve the problem that the first-line drug for the treatment of hyperlipidemia—statin drugs, the increase of PCSK9 leads to the reduction of lipid-lowering activity, the present invention provides an application of a natural drug that reduces the secretion of PCSK9 by liver cells

Method used

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  • Application of saponin compounds capable of reducing PCSK9 secreted by hepatocytes in gynostemma pentaphyllum total glycoside particles
  • Application of saponin compounds capable of reducing PCSK9 secreted by hepatocytes in gynostemma pentaphyllum total glycoside particles
  • Application of saponin compounds capable of reducing PCSK9 secreted by hepatocytes in gynostemma pentaphyllum total glycoside particles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 The preparation method of monomer compound in Gynostemma pentaphyllum from Hunan origin and Guangxi origin

[0034] The medicinal materials of Gynostemma japonica from the two origins were taken separately, extracted twice by decocting method, extracted with 8 times the amount of water for 2 hours each time, the extracts were combined, filtered and concentrated to obtain the total Gynostemma saponin extract. The total saponin extract of Gynostemma pentaphyllum was taken, and ultrasonically extracted with 8 times the amount of methanol for 5 times for 20 min each time. The filtrates were combined and concentrated under reduced pressure to obtain the methanol-soluble fraction. An appropriate amount of methanol-soluble extract was subjected to deactivated silica gel column chromatography, eluted with a gradient of chloroform-methanol-water (100:0:0→0:100:0), checked by TLC, and 5 fractions were combined. (Fr.a~Fr.i). Then repeat silica gel, ODS, Sephadex LH-2...

Embodiment 2

[0060] Example 2 Some monomeric compounds in Gynostemma pentaphyllum from Hunan origin and Guangxi origin have significant PCSK9 reducing activity on HepG2 cells under the condition of 20 μM drug concentration

[0061] Human hepatoma cells (HepG2) were divided into several groups, each group had three parallel wells, and 1*10 cells were inoculated in each well. 5 Cells were inserted into 12-well plates and cultured in DMEM low-glucose medium containing 10% fetal bovine serum in 5% CO. 2 After inoculating cells, these groups of cells were treated as follows: the first group was a blank group, cultured with DMEM low-glucose medium containing 5% fetal bovine serum (FBS), and the second group was The model group was cultured with DMEM low-glucose medium containing 5% lipoprotein-deficient serum (LPDS), and the subsequent groups were the administration groups of different monomer compounds (20 μM), which were cultured with DMEM low-glucose medium containing 5% LPDS. Culture, the b...

Embodiment 3

[0063] Example 3 Some monomeric compounds in Gynostemma pentaphyllum from Hunan origin and Guangxi origin have significant PCSK9 reducing activity on HepG2 cells under the condition of 10 μM drug concentration and total Gynostemma glycosides

[0064] Human hepatoma cells (HepG2) were divided into several groups, each group had three parallel wells, and 1*105 cells were inoculated into 12-well plates in each well, and cultured in DMEM low-glucose medium containing 10% fetal bovine serum. %CO2 in a 37°C incubator; after inoculation, these groups of cells were treated as follows: the first group was a blank group, cultured with DMEM low-glucose medium containing 5% FBS, and the second group was a model group, Cultured with DMEM low-glucose medium containing 5% LPDS, and then several groups were respectively treated with different monomer compounds (10 μM) or total glycosides (50 μg / mL) were cultured with DMEM low-sugar medium containing 5% LPDS, The blank group was treated for 48...

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Abstract

The invention relates to the technical field of natural medicinal chemistry, in particular to application of saponin compounds capable of reducing PCSK9 secreted by hepatocytes in gypenosides granules. The invention discloses novel application of gynostemma pentaphyllum, and particularly relates to application of monomeric compounds in gynostemma pentaphyllum produced in Hunan and Guangxi to reduction of activity of PCSK9 secreted by hepatocytes. Part of monomeric compounds in gynostemma pentaphyllum produced in Hunan and Guangxi areas have different degrees of inhibitory activity on PCSK9 secreted by hepatocytes, so that the purpose of lowering lipid alone or enhancing the lipid lowering effect by cooperating with statins is achieved.

Description

[0001] This application is a divisional application with an application number of 2020112777401 and an application date of November 16, 2020, and the title of the invention is "Application of saponins in Gynostemma Gynostemma granules to prepare drugs that inhibit PCSK9 from exerting lipid-lowering effect". technical field [0002] The invention relates to the technical field of natural medicinal chemistry, in particular to a dammarane-type triterpenoid saponin compound isolated from Gynostemma pentaphyllum from Hunan and Guangxi and its application in the preparation of a drug for inhibiting PCSK9 and exerting lipid-lowering effect. Background technique [0003] Hypercholesterolemia is a major risk factor for atherosclerosis and heart disease, and low-density lipoprotein cholesterol (LDL-C) has been identified as an independent and most potent modifiable risk factor for the development of cardiovascular disease. [0004] Over the past 20 years, statin use has successfully re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61K45/06A61K31/366A61P3/06
CPCA61P3/06A61K31/7048C07H1/08C07H17/07A61K31/704C07H15/256C07J17/005C07J71/0005
Inventor 姜新宇刘朝辉张增勤
Owner 湖南华宝通制药有限公司
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