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Application of cocoa extract in preparation of medicine for resisting aging and inhibiting tumors

A kind of extraction and aging technology, applied in the field of biomedicine, can solve the problem that human lung fibroblasts are less effective

Active Publication Date: 2021-06-01
徐州奇诺医疗科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, in human lung fibroblasts, navitoclax was able to target and kill senescent cells in the culture-adapted IMR90 lung fibroblast-like cell line, but was less effective in senescent primary human lung fibroblasts

Method used

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  • Application of cocoa extract in preparation of medicine for resisting aging and inhibiting tumors
  • Application of cocoa extract in preparation of medicine for resisting aging and inhibiting tumors
  • Application of cocoa extract in preparation of medicine for resisting aging and inhibiting tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0196] Example 1, CCE can effectively inhibit the expression of SASP when used at a low concentration

[0197] To identify novel compounds that can effectively modulate the phenotype of senescent cells, the inventors performed an unbiased screen using a natural raw material drug library consisting of 68 plant derivatives. In order to test the efficacy and potential biological value of these drugs, the primary normal human prostate stromal cell line, PSC27, was chosen as an in vitro cell model. Composed primarily of fibroblasts, with non-fibroblastic cell lines (including endothelial cells and smooth muscle cells) also present, but in smaller proportions, PSC27 is a primary stromal cell line of human origin in nature and responds after exposure to genotoxic chemotherapy or Typical SASP is formed after stress factors such as ionizing radiation. These cells were treated with a specific dose of bleomycin (BLEO) in the optimized way in the preliminary experiment, and the positive ...

Embodiment 2

[0200] Example 2. CCE is a new type of senolytics when used in high concentrations

[0201] Given the remarkable efficacy of CCE in controlling SASP expression, it is necessary to next explore the potential of this natural product to kill senescent cells at higher concentrations. To this end, the present inventors determined the survival percentage of PSC27 senescent cells treated under in vitro conditions (50 μg / ml BLEO treatment induced cell senescence) with increasing CCE concentration. SA-β-GAL staining data indicated that senescent cells were not eliminated until the CCE concentration reached 200 μM ( Figure 12 ). As the concentration increases, the killing effect of CCE on senescent cells (80% staining positive) is further enhanced, and when CCE reaches the threshold at 800 μM (20% of senescent cells remain at this time); when its concentration increases to 1000 μM, CCE The killing effect of the is not further enhanced ( Figure 12 ; Figure 13 ).

[0202] In order...

Embodiment 3

[0207] Example 3. Using CCE to therapeutically target senescent cells can promote tumor regression and effectively reduce chemotherapy resistance

[0208] In view of the outstanding selectivity of CCE in clearing senescent cells at higher concentrations in vitro, the inventors next considered whether this drug could be used to intervene in vivo in aging-related diseases. Cancer is one of the major chronic diseases that seriously threaten human life and endanger health. In addition, cancer cell drug resistance limits the efficacy of most anticancer therapies in the clinic, and senescent cells often promote therapeutic drug resistance by developing SASPs in damaged tumor foci. Even so, the feasibility and safety of removing senescent cells from primary tumors to promote a therapeutic index of cancer has been largely unexplored to date.

[0209] First, the inventors constructed tissue recombinants by mixing PSC27 stromal cells with PC3 epithelial cells, which is a typical highly...

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Abstract

The invention provides an application of a cocoa extract in preparation of a medicine for resisting aging and inhibiting tumors, and discloses that the cocoa extract (CCE) acts on a tumor microenvironment through targeting to remove aging cells and can promote tumor inhibition by removing aging stromal cells. The CCE can also remove senescent cells in a senescence-related secretory phenotype (SASP) in a targeted manner, so that the SASP is inhibited. The CCE can also significantly prolong the life of animals, significantly prolong the lifetime of old people, and improve the life quality of animals.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically, the invention relates to the application of cocoa extract in the preparation of anti-aging and anti-tumor drugs. Background technique [0002] Cellular senescence refers to a relatively stable and often irreversible state of cell cycle arrest in eukaryotic cells, in which proliferating cells become resistant to growth-promoting stimuli, usually induced by stress signals such as DNA damage. Replicative senescence of cells refers to the fact that normal cells cease to divide continuously after about 30-50 divisions (the "Hayflick limit"). Replicative senescence is essentially induced by progressive shortening of telomeres. With each round of DNA replication, telomeres gradually shorten, eventually reaching a critical length that prevents further replication and thus stops cell division. Shorter uncapped telomeres elicit a DNA damage response that directly triggers senescence. ...

Claims

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Application Information

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IPC IPC(8): A61K36/185A61K31/136A61K38/14A61K31/704A61P35/00A61P39/00C12Q1/02
CPCA61K36/185A61K31/136A61K38/14A61K31/704A61P35/00A61P39/00G01N33/5011G01N33/5008A61K2236/19A61K2236/333A61K2236/53A61K2300/00
Inventor 孙宇丁正兵
Owner 徐州奇诺医疗科技有限公司
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