Applications of naringenin and naringin as signal pathway inhibitor of transforming growth factor-beta 1

A transforming growth factor and signaling pathway technology, applied in the application field of inhibitors in the pharmaceutical field, can solve problems such as lack of ideal drugs

Active Publication Date: 2008-12-17
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Current treatments targeting the TGF-β signaling pathway include altered immune components, small molecule inhibitors, soluble protein and antisense complex inhibitors, but there is no drug that inte

Method used

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  • Applications of naringenin and naringin as signal pathway inhibitor of transforming growth factor-beta 1
  • Applications of naringenin and naringin as signal pathway inhibitor of transforming growth factor-beta 1
  • Applications of naringenin and naringin as signal pathway inhibitor of transforming growth factor-beta 1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1. Effect of naringenin on the proliferation of rat hepatic stellate cells and the secretion of cell matrix collagen

[0045] Experimental method: Rat hepatic stellate cells (HSC-T6, Hepatic stellate cell, provided by Professor Friedman of Mount Sinai Medical Center, USA) were cultured in a medium containing 10% fetal bovine serum (US PPA company), 100 U / ml of penicillin and streptomycin RPMI1640 medium (Sigma), 5% CO 2 , 37°C (FIL-TER incubator, Thermo Company, Germany). Digest cells with an abundance of 90% with 0.25% trypsin and adjust the number of cells to 5×10 4 / ml, inoculate 100 μl / well in 96-well culture plate, supplement the culture medium containing different concentrations of naringenin 100 μl / well after the cells adhere overnight, 4-6 duplicate wells for each concentration, continue to culture for 48 hours, remove the culture medium Add 0.5 mg / ml MTT (dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (Sigma company) to 100 μl / well of phosphate...

Embodiment 2

[0047] Embodiment 2. Naringenin is to carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice

[0048] Experimental method: Female balb / c mice (provided by Beijing Weitong Lihua Experimental Animal Company) were subcutaneously injected with 10% CCl 4 (carbon tetrachloride), 0.2ml / mouse, 2 times a week, for 4 consecutive weeks to induce liver fibrosis model. From the second week, the treatment group was given naringenin (Nar) high (100mg / kg), medium (50mg / kg) and low (25mg / kg) three doses by intragastric administration (ig), or intravenous injection (iv) 5mg / kg and subcutaneous injection (sc) 20mg / kg for treatment, another group of mice without fibrosis model was set as normal control mice, 10 mice in each group, administered once a day for 3 consecutive weeks. On the 28th day, blood was collected from the orbital vein for blood index detection, and then the mice were sacrificed, and the liver was removed and weighed. In this example, the MDA, CAT and POD kits were pur...

Embodiment 3

[0050] Example 3. Effect of naringenin on the growth of mouse liver cancer H22 subcutaneous tumor

[0051] Experimental method: After making cell suspension with PBS from mouse liver cancer H22 subcutaneous tumor (provided by Institute of Materia Medica, Chinese Academy of Medical Sciences), the number of cells was adjusted to 5×10 6 / ml, inoculated subcutaneously in the forelimb armpit of female balb / c mice with 0.2ml / only. The next day after tumor inoculation, the treatment group was administered with naringenin (Nar) 200mg / kg, 100mg / kg and 50mg / kg orally (ig) 3 doses or intravenously (iv) 20mg / kg, 10mg / kg and 5mg / kg3 Each dose or subcutaneous injection (sc) 40mg / kg, 20mg / kg and 10mg / kg three doses of treatment, 10 mice in each group, administered once a day, for 2 consecutive weeks. After growing out from the tumor, the tumor volume was measured with a vernier caliper every 2 days, expressed as length×width×0.5 width, and the tumor growth curve was drawn.

[0052] Results...

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Abstract

The invention discloses the application of naringenin and aurantiin as the inhibitor of the signal passage of transforming growth factor-Beta1, in particular the application to the treatment or prevention of fibrosis and tumors.

Description

technical field [0001] The present invention relates to the application of naringenin and naringin, especially the application as an inhibitor of transforming growth factor-β1 (transforming growth factor betal, referred to as TGF-β1) signal pathway in the field of pharmacy. Background technique [0002] Fibrosis is the common pathological basis of various chronic diseases and an important intermediate link in tissue and organ sclerosis and even tumorigenesis. The pathological process of abnormal growth and excessive deposition is characterized by a large amount of fibrous tissue proliferation and precipitation, and the collagen content increases by 4 to 7 times [Won-Il Jeong et al,, Hepatology, 44(6):1441-1451, (2006)]. In the process of tissue and organ fibrosis, fibroblasts are the basis of various appearances of regional fibrosis. Activated fibroblasts have a strong ability to produce and recombine collagen, and some cytokines in tissue damage or inflammation, such as cel...

Claims

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Application Information

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IPC IPC(8): A61K31/352A61K31/7048A61P35/00A61P1/16A61P11/00
CPCA61K31/352A61K31/7048A61P1/16A61P11/00A61P35/00A61P35/04A61P43/00
Inventor 梁伟杜钢军张鸿雁金凌涛吕和平王伟刘金平樊振
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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