Application of 15-benzylidene-14-deoxy-11,12-dehydroandrographolide derivatives in anti-fibrosis drugs

A technology of andrographolide and myocardial fibrosis, which is applied in the field of medicine, achieves good application and development prospects, improves the effect of organ fibrosis, and expands the effect of selection

Active Publication Date: 2021-07-02
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Further research on the activity of 15-benzylidene-14-deoxy-11,12-dehydroandrographolide derivatives in the fibrosis of other tissues (organs) except the liver, there is no relevant literature report

Method used

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  • Application of 15-benzylidene-14-deoxy-11,12-dehydroandrographolide derivatives in anti-fibrosis drugs
  • Application of 15-benzylidene-14-deoxy-11,12-dehydroandrographolide derivatives in anti-fibrosis drugs
  • Application of 15-benzylidene-14-deoxy-11,12-dehydroandrographolide derivatives in anti-fibrosis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1 Compounds of the present invention inhibit the mesenchymal transition of human type II alveolar epithelial cells A549

[0064] The type II alveolar epithelial cells existing in the alveoli are stimulated by cytokines such as inflammatory mediators and growth factors, and the cell shape changes from cobblestone-like to spindle-like, completing the process of epithelial-mesenchymal transition (EMT) and having the function of mesenchymal cells. , and then synthesize collagen fibers, and the deposition of a large number of collagen fibers can aggravate the course of pulmonary interstitial fibrosis. Therefore, compared with andrographolide, human type II alveolar epithelial cells A549 were used to evaluate the in vitro anti-pulmonary fibrosis effect of the compounds of the present invention by morphological observation and cell scratch (migration) experiments.

[0065] 1) Cell culture

[0066] A549 cells were cultured in RPMI1640 medium containing 10% (V / V) fetal ...

Embodiment 2

[0076] Example 2 The compounds of the present invention inhibit TGF-β1-induced mesenchymal transition of human renal cortical proximal tubule epithelial cells HK-2

[0077] Early studies found that renal tubular epithelial cells can transdifferentiate into fibroblasts and express their marker protein fibroblast-specific protein 1 (FSP1, fibroblast-specific protein 1). one of the important pathogenic mechanisms of Therefore, compared with andrographolide AD, using human renal cortex proximal tubule epithelial cells HK-2 (provided by the China Center for Type Culture Collection), the compounds of the present invention were studied by morphological observation method and scratch experiment after stimulation by TGF-β1 In vitro anti-renal fibrosis effect.

[0078] 1) Cell culture

[0079] HK-2 cells were cultured in DMEM-F12 medium containing 10% fetal bovine serum (V / V), 100 μg / mL streptomycin, and 100 IU / mL penicillin, and placed in a volume fraction of 5% CO. 2 In an incubato...

Embodiment 3

[0090] Example 3 The compound of the present invention inhibits the proliferation of human primary cardiac fibrosis cells HCFB induced by angiotensin II (Ang II)

[0091] Studies have shown that myocardial fibroblasts are the main effector cells of myocardial fibrosis. After being stimulated by active substances such as Ang II, they will proliferate in number, and their phenotype will be transformed into myofibroblasts with the function of secreting extracellular matrix. Therefore, the anti-cardiac fibrosis effect of the compound H of the present invention was evaluated by detecting the cytostatic effect of Ang II stimulated primary human cardiac fibroblasts HCFB by MTT method.

[0092] 1) Cell culture

[0093] Using primary human cardiac fibroblasts HCFB (provided by Shangcheng Beina Chuanglian Biotechnology Co., Ltd.), compared with andrographolide, the in vitro anti-myocardial fibrosis effect of the compound H of the present invention was studied. The HCFB cells were cultu...

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Abstract

The invention belongs to the technical field of medicine, and discloses the application of 15-benzylidene-14-deoxy-11,12-dehydroandrographolide derivatives in the preparation of drugs for preventing and treating human organ or tissue fibrosis. Experiments have proved that these compounds significantly inhibit TGF-β1-induced mesenchymal transition of human alveolar type II epithelial cells A549; significantly inhibit TGF-β1-induced mesenchymal transition of human renal cortical proximal tubule epithelial cells HK-2; inhibit Angiotensin Ⅱ (Ang Ⅱ)-induced proliferation of human primary cardiac fibrosis cells HCFB. Significantly reduce the degree of bleomycin-induced pulmonary fibrosis in mice, significantly reduce the degree of renal fibrosis in rats induced by unilateral ureteral ligation and the degree of myocardial fibrosis in Kunming mice induced by isoproterenol ISO. Using this type of compound as an active ingredient to prepare anti-fibrosis drugs such as kidney, lung, heart, etc., has high efficiency and low toxicity, and provides a new drug approach for the treatment and prevention of diseases related to fibrosis, thereby expanding the choice of clinical medication range, has a good prospect for application development.

Description

technical field [0001] The invention relates to the application of andrographolide derivatives as anti-fibrotic drugs for human organs or tissues, in particular to 14-deoxy-11,12-dehydroandrographolide C15 substituted derivatives, belonging to the technical field of medicine. Background technique [0002] Tissue fibrosis is a chronic disease that occurs mostly in the liver, lung, heart, kidney and other parts. Tissue fibrosis and resulting organ failure are responsible for 1 / 3 of people worldwide. When tissue is injured, a series of cellular reactions occur at the injury site, resulting in excessive deposition of extracellular matrix and tissue fibrosis. It can eventually lead to organ dysfunction and even death. Cardiovascular fibrosis plays an important role in cardiovascular tissue remodeling caused by hypertension and heart failure, and is also the main cause of atherosclerosis. Cardiac fibrosis is characterized by accumulation of extracellular matrix proteins in the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/365A61P11/00A61P13/12A61P9/00
Inventor 戴桂馥王亚可徐海伟赵安琪赵进张淑秋王丙顺
Owner ZHENGZHOU UNIV
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