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Use of PGC-1 alpha activator daucosterol in preparing medicine for preventing and treating blood brain barrier injury

A technology of blood-brain barrier damage and carotene, which is applied in the field of medicine to achieve the effect of protection from damage

Active Publication Date: 2021-08-06
HUAZHONG AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Carotin (structural formula below) activates the transcription of PGC-1α, however, its application in the treatment of blood-brain barrier damage has not been reported

Method used

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  • Use of PGC-1 alpha activator daucosterol in preparing medicine for preventing and treating blood brain barrier injury
  • Use of PGC-1 alpha activator daucosterol in preparing medicine for preventing and treating blood brain barrier injury
  • Use of PGC-1 alpha activator daucosterol in preparing medicine for preventing and treating blood brain barrier injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 Carotin activates the expression of PGC-1α in vivo and in vitro

[0027] 1. Materials and Reagents

[0028] 1.1 Materials

[0029] The cell line used in this experiment is human brain microvascular endothelial cells hBMEC cells. The experimental animals were healthy SPF female Kunming mice purchased from the Experimental Animal Research Center of Huazhong Agricultural University.

[0030] 1.2 Main reagents

[0031] T-2 toxin: CAS No. 21259-20-1, purity 99.9%, purchased from Fermentek, Israel; LPS (Ultrapure, TLR4 activator): Product No. S1735, purchased from Shanghai Biyuntian Biotechnology Co., Ltd.; rabbit anti-β -tubulin polyclonal antibody: Cat. No. #2128, purchased from CST, USA; rabbit anti-PGC-1α polyclonal antibody: Cat. No. NBP1-04676, purchased from Novus, USA; HRP Goat Anti-Rabbit IgG (H+L): Cat. No. AS014 , purchased from Wuhan Aibotec Biotechnology Co., Ltd.

[0032] 2. Test method

[0033] 2.1 Cell culture

[0034] hBMEC cells are human br...

Embodiment 2

[0063] Example 2 Carotin Alleviates the Increase of NaF Content Caused by T-2 Toxin and LPS Toxicity

[0064] 1. Materials and Reagents

[0065] 1.1 Materials

[0066] The cell line used in this experiment is human brain microvascular endothelial cells hBMEC cells. The experimental animals were healthy SPF female Kunming mice purchased from the Experimental Animal Research Center of Huazhong Agricultural University.

[0067] 1.2 Main reagents

[0068] T-2 toxin: CAS No. 21259-20-1, purity 99.9%, purchased from Fermentek, Israel; LPS (Ultrapure, TLR4 activator): Product No. S1735, purchased from Shanghai Beyond Biotechnology Co., Ltd.; sodium fluorescein : Cat. No. F809553, purchased from McLean Biotech.

[0069] 2. Test method

[0070] 2.1 Cell culture

[0071] hBMEC cells are human brain microvascular endothelial cell lines, which grow in the shape of paving stones and adhere to the wall. Use RPMI-1640 complete culture medium (containing 10% FBS, 1% glutamine, 1% doubl...

Embodiment 3

[0090] Example 3 Carotin alleviates the reduction of cell compactness caused by T-2 toxin and LPS toxicity

[0091] 1. Materials and Reagents

[0092] 1.1 Materials

[0093] The cell line used in this experiment is human brain microvascular endothelial cells hBMEC cells.

[0094] 1.2 Main reagents

[0095] T-2 toxin: CAS No. 21259-20-1, purity 99.9%, purchased from Fermentek, Israel; LPS (Ultrapure, TLR4 activator): Product No. S1735, purchased from Shanghai Biyuntian Biotechnology Co., Ltd.; rabbit anti-β -tubulin polyclonal antibody: product number #2128, purchased from CST, USA; rabbit anti-ZO-1 polyclonal antibody: product number A0659, purchased from China Abclonal Company; rabbit anti-CLDN5 polyclonal antibody: product number A10207, purchased from China Abclonal Company; Rabbit anti-occludin polyclonal antibody: product number A2601, purchased from China Abclonal Company; HRP Goat Anti-Rabbit IgG (H+L): product number AS014, purchased from Wuhan Aibtech Biotechnology...

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PUM

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Abstract

The invention discloses use of daucosterol and isomers or pharmaceutically acceptable salts thereof in preparing a medicine for resisting blood brain barrier injury. The daucosterol can increase expression of PGC-1 alpha in vivo and in vitro and relieve transmembrane resistance reduction and cell permeability increase caused by exogenous factors, such that tightness of the blood brain barrier is improved. In-vitro cell test results show that the daucosterol can increase expression of a blood brain barrier tight junction protein, increase close connection between cells and relieve blurred cell membrane and intercellular connection caused by exogenous factors. An animal in-vivo blood brain barrier injury model is constructed, an influence of the daucosterol on in-vivo brain tissue injury is detected, and the result shows that the daucosterol can relieve brain tissue injury caused by exogenous factors, increase expression of the blood brain barrier tight junction protein, reduce expression of brain inflammatory factors, and thus relieve the blood brain barrier injury.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to the application of PGC-1α activator carotin in the preparation of medicines for preventing and treating blood-brain barrier damage. Background technique [0002] PGC-1α, a member of the PGC-1 family, was originally isolated from brown adipose tissue and defined as a protein that interacts with the peroxisome proliferator-activated receptor, a potent mitochondrial Activator of biosynthesis and respiration. PGC-1α is particularly abundant in brain regions such as the cerebral cortex, striatum and globus pallidum, substantia nigra. [0003] PGC-1α has a protective effect in various nervous system injuries. PGC-1α is closely related to brain diseases and plays a protective role in blood-brain barrier damage caused by various diseases. Studies have shown that in the stroke-induced oxygen-glucose deprivation model, PGC-1α together with the up-regulated Sirt3 inhibits the oxidative stress induce...

Claims

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Application Information

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IPC IPC(8): A61K31/704A61P25/00
CPCA61K31/704A61P25/00
Inventor 王旭郭璞陶燕飞谢书宇陈冬梅谢长清
Owner HUAZHONG AGRI UNIV
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