CN106822217B - Application of cranberry freeze-dried powder in preparation of medicine for preventing and treating familial adenomatous polyposis - Google Patents

Application of cranberry freeze-dried powder in preparation of medicine for preventing and treating familial adenomatous polyposis Download PDF

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CN106822217B
CN106822217B CN201710089659.2A CN201710089659A CN106822217B CN 106822217 B CN106822217 B CN 106822217B CN 201710089659 A CN201710089659 A CN 201710089659A CN 106822217 B CN106822217 B CN 106822217B
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cranberry
preventing
dried powder
medicine
adenomatous polyposis
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CN106822217A (en
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曹海龙
王邦茂
金多晨
王斯南
董文逍
刘天宇
王伟强
朴美玉
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Tianjin Medical University General Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/45Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions

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  • Mycology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses application of cranberry freeze-dried powder in preparation of a medicine for preventing and treating familial adenomatous polyposis. The cranberry freeze-dried powder provided by the invention is used as a dietary supplement which can directly inhibit the growth of polyps, has a definite curative effect and no side effect, and has very important significance for clinical prevention and treatment of FAP, improvement of the life quality of patients and reduction of relapse. The invention provides a safe, effective and economical new method for preventing and treating FAP and sporadic intestinal polyp, and has wide application prospect.

Description

Application of cranberry freeze-dried powder in preparation of medicine for preventing and treating familial adenomatous polyposis
Technical Field
The invention relates to a new application of cranberry, in particular to an application of cranberry freeze-dried powder in preparation of a medicine for preventing and treating familial adenomatous polyposis.
Background
Familial Adenomatous Polyposis (FAP) is an autosomal dominant genetic disease characterized by multiple adenomatous polyposis of the digestive tract, the onset of which is primarily associated with Apc mutations. Due to the special genetic background of FAP, the FAP is frequently and easily cancerized, and has become one of the hot spots in the research field of large intestine diseases. At present, a FAP prevention and treatment method with ideal curative effect and safety is not available. Current methods of prevention include primarily chemopreventive and surgical prophylactic total colectomy with cyclooxygenase-2 (COX-2) inhibitors. Celecoxib is the only approved chemopreventive drug by FDA in the united states, with an effective rate of only about 30%. The problems of low effective rate, easy polyp recurrence, serious side effect, pharmacogenomics and the like exist in the medicine treatment; the operation can not prevent the polyp canceration of the upper digestive tract and the small intestine, and the problems of serious low life quality and relapse of the patient exist. Therefore, the medicine which can directly inhibit the growth of polyp, has definite curative effect and less side effect is urgently needed to be searched, and has very important significance for the clinical prevention and treatment of FAP, the improvement of the life quality of patients and the reduction of relapse.
Apcmin/+The mouse can spontaneously form multiple adenomas in the intestinal tract due to the mutation of the Apc gene, is widely applied to in vivo research of FAP, and is a good animal model for simulating human FAP. Furthermore, Apcmin/+Mice are also used in the study of various relationships between factors such as various drugs and diets and intestinal tumors.
Cranberry (Cranberry) belongs to Vaccinium of Ericaceae, and is rich in type A Procyanidin (PACs), dietary fiber, ellagitannin, bioflavonoid, and vitamin C, and has excellent antioxidant and free radical scavenging effects. The cranberry can be used for preventing common urinary system infection, reducing incidence of gastric ulcer and gastric cancer, and delaying cardiovascular aging and senile dementia. In recent years, scholars at home and abroad also find that the cranberry has an anti-tumor effect, but the research on preventing and treating FAP is not reported.
Disclosure of Invention
The invention aims to solve the problem that a method for preventing and treating familial adenomatous polyposis with ideal and safe curative effect is lacked at present, and provides application of cranberry freeze-dried powder in preparation of a medicine for preventing and treating familial adenomatous polyposis.
The invention is realized according to the following technical scheme.
An application of cranberry lyophilized powder in preparing medicine for preventing and treating familial adenomatous polyposis is provided.
An edible method of cranberry freeze-dried powder in a medicine for preventing and treating familial adenomatous polyposis comprises the following steps: adding 20-30% cranberry into common diet, and continuously eating for 11-13 weeks.
The present invention obtains the following advantageous effects.
The cranberry freeze-dried powder provided by the invention is used as a dietary supplement which can directly inhibit the growth of polyps, has a definite curative effect and no side effect, and has very important significance for clinical prevention and treatment of FAP, improvement of the life quality of patients and reduction of relapse. The invention provides a safe, effective and economical new method for preventing and treating FAP and sporadic intestinal polyp, and has wide application prospect.
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FIG. 1 shows that the cranberry lyophilized powder of the present invention reduces APCmin/+Mouse tumor burden plot;
FIG. 2 is a graph of cranberry freeze-dried powder versus APC of the present inventionmin/+The mouse intestinal epithelial cell proliferation plays a role in inhibiting;
fig. 3 is a graph of the inhibitory effect of cranberry lyophilized powder on EGFR signaling pathway activation according to the present invention;
fig. 4 is a graph showing the effect of cranberry freeze-dried powder on inhibiting intestinal inflammation.
Detailed Description
The invention is further explained below with reference to the drawings and examples.
The eating method of the cranberry comprises the following steps: administration of 4 week old APCmin/+Mice were fed 20% cranberries (wt/wt) for 12 weeks.
Cranberry versus APCmin/+Experiment on influence of polyp size and quantity in mice
The classical EGFR pathway mainly comprises a ① mitogen-activated protein kinase pathway (Ras/Raf/MEK/ERK/MAPK pathway), a protein kinase 1 (ERK 1), ERK2, JNK/p38-MAPK and the like which are regulated by activating extracellular signals, phosphorylates cytoplasmic proteins, can also enter a cell nucleus to phosphorylate transcription factors, activates the nuclear AP-1 and mainly mediates cell proliferation and differentiation, and a ② phosphatidylinositol 3 kinase (PI 3K) pathway, wherein a product of PI3K is PIP3 to regulate PDK-1 to cause phosphorylation, further regulates the downstream target proteins such as Caspase-9 and NF-kappa B and the like, and plays an important role in the survival and apoptosis of cells.
The present invention provides 4-week-old APCmin/+Mice were divided into two groups: common diet group (AIN-76A) and cranberry lyophilized powder diet group (AIN-76A mixed with 20% cranberry lyophilized powder). Two groups of mice were fed freely without restriction of diet. Fresh feces were collected at 0 and 12 weeks of the experiment for 16s rrna flora detection. Observing and recording the number, size and distribution of the intestinal adenomas under a microscope. HE staining assesses intestinal tumor case types, immunohistochemistry assesses tumor cell proliferation, TUNEL techniques assesses tumor cell apoptosis. The level of intestinal inflammation was assessed by RT-PCR. Immunohistochemistry and WESTERN BLOT assessed activation of the EGFR signaling pathway. The levels of short chain fatty acids SCFAs were determined by gas chromatography of ileocecal intestinal contents.
The invention passes the pair Apcmin/+The intervention discovery that the mice are fed with cranberry freeze-dried powder diet comprises the following steps: the cranberry diet can reduce the total number of intestinal polyps by 33.1 percent, remarkably reduce the size of the intestinal polyps, promote apoptosis while inhibiting the proliferation of tumor cells, inhibit the activation of EGFR and Akt and lower the expression levels of COX-2 and PGE2 in small intestines. Meanwhile, the cranberry can obviously reduce the expression of intestinal inflammatory cytokines (IL-6, IL-9, IFN-gamma and IL-17A), up-regulate the expression level of anti-inflammatory factors (IL-4 and IL-10) (see figures 1-4) and obviously improve the level of short-chain fatty acids SCFAs (acetic acid, propionic acid and butyric acid) in the ileocecal part (see table 1). Small sample clinical research shows that cranberry can inhibit recurrence of FAP patient after endoscopic resection of rectal polyp.
Figure 581509DEST_PATH_IMAGE001

Claims (1)

1. The application of the cranberry freeze-dried powder in preparing the medicine for preventing and treating familial adenomatous polyposis is characterized in that: the addition amount of the cranberry freeze-dried powder is 20%.
CN201710089659.2A 2017-02-20 2017-02-20 Application of cranberry freeze-dried powder in preparation of medicine for preventing and treating familial adenomatous polyposis Active CN106822217B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101951900A (en) * 2008-02-22 2011-01-19 Cm&D制药有限公司 Compositions comprising phytoestrogens selective for estrogen beta receptor and dietary fibres
CN102058590A (en) * 2010-12-27 2011-05-18 天津医科大学总医院 Application of berberine to preparing drug for preventing and treating familial adenomatous polyp
CN105687422A (en) * 2016-03-02 2016-06-22 深圳福山生物科技有限公司 Raspberry composition and application thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130045203A1 (en) * 2010-03-02 2013-02-21 Emory University Uses of Noscapine and Derivatives in Subjects Diagnosed with FAP

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101951900A (en) * 2008-02-22 2011-01-19 Cm&D制药有限公司 Compositions comprising phytoestrogens selective for estrogen beta receptor and dietary fibres
CN102058590A (en) * 2010-12-27 2011-05-18 天津医科大学总医院 Application of berberine to preparing drug for preventing and treating familial adenomatous polyp
CN105687422A (en) * 2016-03-02 2016-06-22 深圳福山生物科技有限公司 Raspberry composition and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
COX-2在直肠腺瘤性息肉与癌组织中的表达及意义;廖湘鲁等;《中国癌症杂志》;20031231;第13卷(第3期);第250-252页 *

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