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Application of 15-benzyl subunit-14-deoxy-11, 12-dehydroandrographolide derivative in anti-fibrosis medicines

A technology of andrographolide and benzylidene, applied in the field of medicine

Active Publication Date: 2019-05-10
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-benzyl subunit-14-deoxy-11, 12-dehydroandrographolide derivative in anti-fibrosis medicines
  • Application of 15-benzyl subunit-14-deoxy-11, 12-dehydroandrographolide derivative in anti-fibrosis medicines
  • Application of 15-benzyl subunit-14-deoxy-11, 12-dehydroandrographolide derivative in anti-fibrosis medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0064] The type II alveolar epithelial cells present in the alveoli are stimulated by cytokines such as inflammatory mediators and growth factors, and the cell shape changes from pebble-like to spindle-like, completing the epithelial-mesenchymal transition (EMT) and possessing the function of mesenchymal cells , and then synthesize collagen fibers, a large amount of collagen fiber deposition can aggravate the course of pulmonary interstitial fibrosis. Therefore, compared with andrographolide, human type II alveolar epithelial cells A549 were used to evaluate the anti-pulmonary fibrosis effect of the compound of the present invention in vitro 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 bovine serum, 100 μg / mL strepto...

Embodiment 2

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

[0077] Early studies have found that renal tubular epithelial cells can transdifferentiate into fibroblasts and express their marker protein fibroblast-specific protein 1 (FSP1, fibroblast-specific protein 1), renal tubular epithelial cells-mesenchymal cell transdifferentiation is the key factor for renal interstitial fibers One of the important pathogenesis of cancer. Therefore, compare with andrographolide AD, utilize human renal cortex proximal tubule epithelial cell HK-2 (provided by China Center for Type Culture Collection), adopt TGF-β1 stimulated morphological observation method and scratch experiment to study the compound of the present invention 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 ...

Embodiment 3

[0090] Example 3 Compounds of the present invention inhibit 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 transform into myofibroblasts with the function of secreting extracellular matrix. Therefore, MTT method was used to detect the inhibitory effect of Ang II on the stimulation of primary human cardiac fibroblasts HCFB to evaluate the anti-myocardial fibrosis effect of the compound H of the present invention.

[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 compound H of the present invention was studied. HCFB cells were culture...

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Abstract

The invention belongs to the technical field of medicines, and discloses application of a 15-benzyl subunit-14-deoxy-11, 12-dehydroandrographolide derivative in preparing medicines for preventing andtreating fibrosis in human organs or tissues. Experiments prove that the compound can obviously inhibit epithelial-mesenchymal transition of human alveolar II epithelial cells A549 induced by TGF-beta1 and epithelial-mesenchymal transition of human renal cortical proximal tubular epithelial cells HK-2 induced by TGF-beta1, inhibit the proliferation of human primary myocardial fibrosis cells HCFB induced by angiotensin II (AngII), and obviously reduce the degree of pulmonary fibrosis induced by bleomycin in mice, the degree of renal fibrosis induced by unilateral ureteral ligation in mice and the degree of myocardial fibrosis caused by isoproterenol ISO in Kunming mice. The compound is used as an active ingredient for preparing anti-fibrosis medicines for organs such as kidney, lung, heartand the like, has high efficiency and low toxicity, provides a new medicine way for treating and preventing fibrosis-related diseases, thereby enlarging the selection range of clinical medication andhaving good application and development prospects.

Description

technical field [0001] The invention relates to the application of andrographolide derivatives as medicines against human organ or tissue fibrosis, 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, mainly in the liver, lung, heart, kidney and other parts. One-third of people worldwide die from tissue fibrosis and the resulting organ failure. When the tissue is damaged, a series of cellular reactions occur at the damaged site, leading to excessive deposition of extracellular matrix and tissue fibrosis. Ultimately, organ dysfunction and even death can result. Cardiovascular tissue 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 the accumulation of extracellular matrix proteins in the ...

Claims

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Application Information

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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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