阅读说明：本技术 一种双黄酮类化合物的应用 (A kind of application of bis-flavonoid ) 是由 宋健平 黄新安 邓长生 徐勤 王琪 张红英 于 2019-09-10 设计创作，主要内容包括：本发明公开了一种双黄酮类化合物的应用,主要是式(1)所示化合物在制备治疗结肠炎药物中的应用,<Image he="385" wi="700" file="RE-DDA0002234535490000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中,R<Sub>1</Sub>为氢或羟基。将该化合物作用于DSS诱导的小鼠肠炎,可以发现该化合物能够改善小鼠结肠炎的症状,说明该化合物对于结肠炎有良好的治疗效果,可以应用于治疗结肠炎药物的制备,扩大了该药物的应用范围。(The invention discloses a kind of application of bis-flavonoid, mainly compound shown in formula (1) treats the application in colitis drug in preparation, Wherein, R 1 For hydrogen or hydroxyl.The mouse enteritis that the compound effects are induced in DSS, it can be found that the compound can improve the symptom of mouse colitis, illustrate that the compound has good therapeutic effect for colitis, can be applied to the preparation for the treatment of colitis drug, expand the application range of the drug.)

1. a kind of application of the compound shown in formula (1) in preparation treatment colitis drug,

Wherein, R₁For hydrogen or hydroxyl.

2. application according to claim 1, which is characterized in that the colitis is ulcerative colitis,

Preferably, any one of compound in following compounds:

Or

3. application according to claim 1, which is characterized in that the drug is to reduce inflammatory factor using the compound The drug of content.

4. application according to claim 1, which is characterized in that the drug is to inhibit IL- β, IL- using the compound 6 and TNF-α mRNA expression drug.

5. application according to claim 1, which is characterized in that the drug be using the compound promoted Nqol, The drug of the mRNA expression of NRF2, SIRT6 and Gclm.

6. application according to claim 1, which is characterized in that the compound is to extract to obtain from Garcinia maingayii Substance, it is preferable that the Garcinia maingayii is that gamboge is laughable；It is highly preferred that extracting the seed that raw material is gamboge cola；

Preferably, extracting method is isolated and purified again after being extracted using organic solvent；

It is highly preferred that organic solvent is alcoholic solvent, preferably monoalcohol solvent, further preferably C1-C3 monoalcohol solvent, more The alcohol solvent that preferably alcohol solvent, most preferably mass percent are 95%；

Preferably, isolate and purify is isolated and purified using chromatographic column.

7. compound shown in a kind of formula (1) improves the application in Intestinal mucosal barrier drug in preparation.

8. application according to claim 7, which is characterized in that the drug is to reduce intestinal mucosa using the compound The drug of permeability.

9. application according to claim 7, which is characterized in that the drug is inhibited on intestinal mucosa using the compound The drug of the mRNA expression of chrotoplast tight junction protein ZO1 and Occludin.

10. a kind of application of the compound shown in formula (1) in the drug that preparation improves large intestine shortening or hematochezia.

Technical field

The present invention relates to medicine technology fields, in particular to a kind of application of bis-flavonoid.

Background technique

Inflammatory bowel disease (enteritis) is the non-specific enteritis that the cause of disease is still not clear, be induce intestinal cancer high risk cause a disease because One of element, gradually development is very popular one of disease for the whole world 5.About 15% enteritis patient is estimated most according to the World Health Organization Cause cancer to occur and shift eventually, seriously threatens the healthy and safe of patient.Therefore, the generation and development for controlling enteritis are preventing Intestinal cancer caused by inflammation plays an important role.However, although causing grinding for intestinal cancer with control enteritis and enteritis over more than 20 years Study carefully and has obtained many progress, but till now, the clinical therapeutic efficacy of enteritis is still undesirable.It is anxious to the disease at present The drug therapy of property phase, mainly colchicin, non-steroidal anti-inflammatory drugs and hormone etc., but such drug dose is larger, side effect More, many patients are not resistant to.It is good that traditional Chinese medicine treats enteritis clinical efficacy, and side effect is less, is easy to be accepted by patients. But do not record which kind of single compound in Chinese medicine has good therapeutic effect to enteritis in the prior art.

In consideration of it, the present invention is specifically proposed.

Summary of the invention

The purpose of the present invention is to provide a kind of application of bis-flavonoid, which has colitis good Good therapeutic effect.

In a first aspect, the embodiment of the present invention provides compound shown in a kind of formula (1) in preparation treatment colitis drug Using,

Wherein, R₁For hydrogen or hydroxyl.

In alternative embodiments, the colitis is ulcerative colitis；

Preferably, any one of compound in following compounds:

Or

In alternative embodiments, the drug is the drug that Inflammatory Factors Contents are reduced using the compound.

In alternative embodiments, the drug inhibits IL- β, IL-6 and TNF-α using the compound The drug of mRNA expression.

In alternative embodiments, the drug is to promote Nqol, NRF2, SIRT6 and Gclm using the compound MRNA expression drug.

In alternative embodiments, the compound is the substance extracted from Garcinia maingayii, it is preferable that The Garcinia maingayii is that gamboge is laughable；It is highly preferred that extracting the seed that raw material is gamboge cola；

Preferably, extracting method is isolated and purified again after being extracted using organic solvent；

It is highly preferred that organic solvent is alcoholic solvent, preferably monoalcohol solvent, further preferably C1-C3 monohydric alcohol is molten The alcohol solvent that agent, more preferably alcohol solvent, most preferably mass percent are 95%；

Preferably, isolate and purify is isolated and purified using chromatographic column.

Second aspect, the embodiment of the present invention, which provides compound shown in a kind of formula (1), improves intestinal mucosal barrier function in preparation Application in energy drug.

In alternative embodiments, the drug is the drug that intestinal membrane permeation is reduced using the compound.

In alternative embodiments, the drug is to inhibit intestinal epithelial cell closely to connect using the compound Connect the drug of the mRNA expression of albumen ZO1 and Occludin.

The third aspect, the embodiment of the present invention, which provides compound shown in a kind of formula (1) and improves large intestine in preparation, to be shortened or just Application in the drug of blood.

The invention has the following advantages: by the mouse enteritis that above compound is acted on to DSS induction, it can be with It was found that the compound can improve the symptom of mouse colitis, illustrate that the compound has good therapeutic effect for colitis, The preparation that can be applied to treatment colitis drug, expands the application range of the drug.

Detailed description of the invention

In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment Attached drawing is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not to be seen as It is the restriction to range, it for those of ordinary skill in the art, without creative efforts, can be with Other relevant attached drawings are obtained according to these attached drawings.

Fig. 1 is the experimental result picture of experimental example 1 of the present invention；

Fig. 2 is the experimental result picture of experimental example 2 of the present invention；

Fig. 3 is the experimental result picture of experimental example 3 of the present invention；

Fig. 4 is the experimental result picture of experimental example 4 of the present invention；

Fig. 5 is the experimental result picture of experimental example 5 of the present invention；

Fig. 6 is the experimental result picture of experimental example 6 of the present invention；

Fig. 7 is the experimental result picture of experimental example 7 of the present invention；

Fig. 8 is the experimental result picture of experimental example 8 of the present invention.

Specific embodiment

It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer It is recommended that condition carry out.Reagents or instruments used without specified manufacturer is the routine that can be obtained by commercially available purchase Product.

Feature and performance of the invention are described in further detail with reference to embodiments.

The embodiment of the present invention provides a kind of a kind of new application of compound shown in formula (1),

Its

In, R₁For hydrogen or hydroxyl.

Preferably, any one of compound in following compounds:

Or

The compound is by mouse model experiment and uses Real-time round pcr, it was demonstrated that the compound can be used In treatment colitis, especially there is good therapeutic effect to ulcerative colitis, which promotes Nqol, NRF2, SIRT6 With the mRNA expression of Gclm, Inflammatory Factors Contents are reduced, inhibit the mRNA expression of IL- β, IL-6 and TNF-α, it is real Now to the good treatment of colitis, while its side effect is low.And the compound improves Intestinal mucosal barrier improvement large intestine Shorten, especially reduction intestinal membrane permeation has good effect, intestinal epithelial cell can be inhibited closely to connect The mRNA of albumen ZO1 and Occludin are expressed, and expand the application range of the compound.

The compound can be obtained by chemical synthesis, can also be obtained by plant extract, can specifically be planted from Guttiferae The substance extracted in object, it is preferable that the Garcinia maingayii is that gamboge is laughable；It is highly preferred that extracting raw material is that gamboge can Happy seed.The purity that can be guaranteed the compound that extraction obtains using above-mentioned raw materials is more advantageous to and plays its drug effect.

Further, extracting method is isolated and purified again after being extracted using organic solvent；

It is highly preferred that organic solvent is alcoholic solvent, preferably monoalcohol solvent, further preferably C1-C3 monohydric alcohol is molten The alcohol solvent that agent, more preferably alcohol solvent, most preferably mass percent are 95%；

Preferably, isolating and purifying is isolated and purified using chromatographic column, and the filler of chromatographic column is silica gel or octyl Alkanisation silica gel or octadecyl alkanisation silica gel or macroreticular resin or Portugal's coagel.