Use of nobiletin in treatment of calcific aortic valvular disease

A technology of tangerine peel and calcification, which can be used in medical preparations containing active ingredients, cardiovascular system diseases, organic active ingredients, etc. It can achieve the effect of inhibiting valve thickening, inhibiting the proliferation of valve interstitial cells, and delaying valve calcification.

Active Publication Date: 2019-03-15
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, surgery will inevitably bring higher risks to patients, such as high perioperative mortality rate, poor long-term effect, and will also increase the economic burden of patients' families

Method used

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  • Use of nobiletin in treatment of calcific aortic valvular disease
  • Use of nobiletin in treatment of calcific aortic valvular disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1, Construction of TNF-α-induced calcification model of human valve interstitial cells

[0033] Take valvular interstitial cells with a culture density close to 80%, starve them overnight in 2% FBS+DMEM high-sugar culture medium, add 30ng / μl final concentration of TNF-α to the newly prepared osteogenic induction medium to prepare calcification induction medium for culture Starved valve interstitial cells. For the method of TNF-α-induced calcification of human valvular interstitial cells, please refer to the following literature: Yu, Z, Seya, K, Daitoku, K, Motomura, S, Fukuda, I, Furukawa, K.2011.Tumor necrosis factor-alpha Accelerates the calcification of human aortic valve interstitial cells obtained from patients with calcific aortic valve stenosis via the BMP2-Dlx5 pathway. The Journal of pharmacology and experimental therapeutics 337(1):16-23., which is hereby incorporated by reference in its entirety.

Embodiment 2

[0034] Example 2, Nobiletin inhibits human valve interstitial cell proliferation

[0035] The human valve interstitial cell calcification model constructed as in Example 1 above was used, and the human valve interstitial cells were divided into 5 groups, and DMSO, DMSO+TNF-α, DMSO+TNF-α+10μM nobiletin, DMSO were used respectively +TNF-α+20μM nobiletin, DMSO+TNF-α+50μM nobiletin (nobiletin was purchased from Selleck company (https: / / www.selleck.cn / ), catalog number: S233; the concentration is the final concentration in the culture medium) was treated for 48 hours, and the proliferation status of the five groups of cells was investigated by flow cytometry and cell proliferation (EdU) experiments after the treatment.

[0036] Depend on figure 1 a and 1b, it can be seen that the use of DMSO+TNF-α to treat human valve interstitial cells slightly inhibits the proliferation of cells. After adding 10 μM, 20 μM and 50 μM nobiletin, the results of flow cytometry show that the cell prol...

Embodiment 3

[0037] Example 3. Nobiletin inhibits calcification of human valve interstitial cells

[0038] The human valve interstitial cell calcification model constructed as in Example 1 above was used, and the human valve interstitial cells were divided into 4 groups, and DMSO, DMSO+TNF-α, DMSO+TNF-α+10μM nobiletin, DMSO were used respectively +TNF-α+20μM nobiletin for treatment. Quantitative PCR analysis of osteogenic marker genes was performed on the cells of each group treated for 24 hours and 48 hours. After 18 days of treatment, the cells of each group were analyzed by Alizarin red staining.

[0039] Alizarin red S staining was positive after human valve interstitial cells were treated with DMSO+30ng / ml TNF-α for 18 days, showing a significant difference compared with the control (DMSO only) group (*p figure 2 a and 2b). The addition of nobiletin at concentrations of 10 μM and 20 μM to the TNF-α-conditioned medium resulted in a dose-dependent decrease in the positive staining of ...

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Abstract

The invention relates to the field of prevention and/or treatment of calcific aortic valvular disease. The inventors research and find that nobiletin can effectively down-regulate expression of osteogenic differentiation marker genes BMP2 and RUNX2 in valvular interstitial cells, and inhibit calcification of the valvular interstitial cells, thereby inhibiting or delaying valvular calcification, and further provide use of the nobiletin in preparing medicines for prevention and/or treatment of individual calcific aortic valvular disease. The invention provides a new option for non-surgical treatment of the calcific aortic valvular disease.

Description

technical field [0001] The invention relates to the field of prevention and / or treatment of aortic valve calcification, in particular to the use of nobiletin in the prevention and / or treatment of aortic valve calcification. Background technique [0002] Nobiletin is a substance widely distributed in citrus fruits. It is a common food additive with certain anti-inflammatory, anti-oxidant, anti-allergic and anti-tumor effects. In addition, there are only limited reports about nobiletin and vascular diseases, such as: 1. Nobiletin may inhibit the formation of atherosclerotic plaques by inhibiting the proliferation and migration of vascular smooth muscle cells in vitro; 2. Rats with carotid artery balloon injury were administered nobiletin (25mg / kg / d) by intragastric administration, which was confirmed to reduce serum TNF-α and IL-6 levels by regulating the ROS-driven NF-κB pathway, and significantly reduced neonatal Intimal hyperplasia. However, there is no report on the rel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P9/00
CPCA61K31/352A61P9/00
Inventor 许康董念国朱鹏史嘉玮
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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