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Application of withanolide compound in preparation of drug or healthcare product for treating or preventing tumors and neurodegenerative diseases

An ester compound, neurodegenerative technology, used in nervous system diseases, anti-tumor drugs, applications, etc., can solve problems such as the development of ashanolide compounds that have not been seen

Inactive Publication Date: 2013-12-11
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, in many literature reports, there is no report of this type of compound activating the Nrf2 signaling pathway, and no withanide compounds have been developed as chemopreventive agents (drugs) and used for the prevention and treatment of tumors and neurodegenerative diseases report

Method used

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  • Application of withanolide compound in preparation of drug or healthcare product for treating or preventing tumors and neurodegenerative diseases
  • Application of withanolide compound in preparation of drug or healthcare product for treating or preventing tumors and neurodegenerative diseases
  • Application of withanolide compound in preparation of drug or healthcare product for treating or preventing tumors and neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1: 4β-hydroxywithaferin E enhances antioxidative response element (ARE)-dependent luciferase reporter gene expression

[0036] Methods: (1) Construction and culture of human breast cancer cell line MDA-MB-231-Luc

[0037] Human breast cancer cell line MDA-MB-231 was purchased from the American Type Culture Collection (ATCC), using MEM medium containing 10% fetal bovine serum (FBS), 2 mM HEPES and 6 ng / mL insulin, placed at 37 ° C, 5 %CO 2 cultured in an incubator. A 39bp sequence containing an antioxidant response element (ARE) from the upstream of the human NQO1 gene was inserted into the cloning site of the luciferase plasmid (pGL4.22[luc2CP / Puro]). The ARE luciferase plasmid was transfected into MDA-MB-231 cells using the transfection reagent Lipofectamine Plus. After 48 hours, the successfully transfected cells were screened with a medium containing puromycin, and the MDA-MB-231-Luc cell line stably expressing ARE luciferase was constructed.

[0038] (2)...

Embodiment 2

[0041] Example 2: 4β-hydroxy withaferin E enhances antioxidant response element (ARE) dependent dual luciferase reporter gene expression method: dual luciferase reporter gene detection test

[0042] The constructed ARE-dependent luciferase expression plasmid (pGL4.22[luc2CP / Puro]) and Renilla luciferase expression vector [pGL4.74[hRluc / TK] were simultaneously transfected into MDA- MB-231 cells. After 24 hours, different concentrations of test compounds were added and treated for 16 hours, and the activities of firefly luciferase and renilla luciferase were detected by Promega’s dual-luciferase reporter gene detection system, and the activity of renilla luciferase was used as an internal reference.

[0043] Results: The activity of Renilla luciferase was used as an internal reference in the dual luciferase reporter gene detection test, and the results were as follows: figure 2 As shown, 4β-hydroxy withaferin E can dose-dependently induce the expression of ARE-dependent dual l...

Embodiment 3

[0044] Example 3: 4β-hydroxy withaferin E up-regulates the protein expression of Nrf2 and its downstream genes

[0045] Method: Western blot analysis (Western blot) to detect changes in protein levels in cells

[0046] MDA-MB-231 cells were inoculated in a 35 mm diameter petri dish, cultured until the density reached 70% to 80%, and treated with different concentrations of compounds to be tested for 16 hours, washed twice with PBS, added cell lysate (50 μg / ml pH Peptidase, 0.5mM phenylmethylsulfonyl fluoride, 1mM sodium orthovanadate, 10mM sodium fluoride, 10mM β-glycerol phosphate), the protein was collected and the protein concentration was determined by Bradford method. Each sample protein (100 μg) was loaded on the sample, and the protein components were separated by SDS-PAGE, and the protein bands were transferred to the nitrocellulose membrane by electrotransfer method. After the film was sealed with 5% skimmed milk powder solution prepared in TBS at room temperature fo...

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PUM

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Abstract

The invention discloses application of a withanolide compound in preparation of a drug or a healthcare product for treating or preventing tumors and neurodegenerative diseases. The withanolide compound has structural formulas as shown in formula I and optical isomers thereof. The research indicates that the withanolide compounds can be used for activating an Nrf2 signal channel, up regulating expression of NrF2 and downstream antioxidant and II-phase detoxifying enzymes thereof, strengthening the level of glutathione in cells, increasing reducing capacity in cells, promoting elimination of active carbon, restraining lipid peroxidation and lowering cytotoxicity caused by cancerogen arsenic and nerve cell toxicity induced by active oxygen H2O2 to show good chemical prevention effect. And therefore, the withanolide compound and nightshade extract including the withanolide compound have the potential of becoming a chemical prophylactic drug and the healthcare product, and can be used for preparing the corresponding oral preparation and injection by being used as the main ingredient, and also can be used for preventing and treating tumors and neurodegenerative diseases.

Description

technical field [0001] The present invention relates to new uses of withanolides compounds, in particular to the use of such compounds and Solanaceae plant extracts containing such compounds in the preparation of medicines or health products for treating or preventing tumors and neurodegenerative diseases application. Background technique [0002] With the development of society, the improvement of human living standards and the improvement of medical conditions, human life expectancy has been significantly extended, but at the same time, the incidence of malignant tumors and neurodegenerative diseases has also increased year by year, which seriously threatens human health. and a heavy burden on society. On the premise that there is no effective drug to achieve effective treatment of the above diseases, preventing the occurrence of diseases has become an effective coping strategy. [0003] Chemoprevention refers to the use of asymptomatic drugs, nutrients (including inorga...

Claims

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Application Information

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IPC IPC(8): A61K31/585A61P35/00A61P25/28A23L1/29A23L33/00
Inventor 沈涛张唐娜任冬梅
Owner SHANDONG UNIV
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