CN102526030A - Application of 3,3'-diindolylmethane in treating inflammatory bowel disease - Google Patents
Application of 3,3'-diindolylmethane in treating inflammatory bowel disease Download PDFInfo
- Publication number
- CN102526030A CN102526030A CN2010105769407A CN201010576940A CN102526030A CN 102526030 A CN102526030 A CN 102526030A CN 2010105769407 A CN2010105769407 A CN 2010105769407A CN 201010576940 A CN201010576940 A CN 201010576940A CN 102526030 A CN102526030 A CN 102526030A
- Authority
- CN
- China
- Prior art keywords
- inflammatory bowel
- treatment
- indole
- dim
- diindolylmethane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于生物医药技术领域，具体涉及二吲哚甲烷和吲哚-3-甲醇在治疗炎症性肠病中的应用。所述二吲哚甲烷和吲哚-3-甲醇可以有效保护机体免受自由基损伤，阻止自由基导致的黏附分子的表达增加,从而有效减轻炎症性肠病的症状。所述吲哚-3-甲醇和二吲哚甲烷在验证性肠病的动物模型中取得很好的疗效，具有广阔的应用前景。The invention belongs to the technical field of biomedicine, and in particular relates to the application of diindolylmethane and indole-3-carbinol in treating inflammatory bowel disease. The diindolylmethane and indole-3-carbinol can effectively protect the body from free radical damage, prevent free radicals from increasing the expression of adhesion molecules, thereby effectively reducing the symptoms of inflammatory bowel disease. The indole-3-carbinol and diindolylmethane have achieved good curative effect in animal models of confirmed enteropathy, and have broad application prospects.
Description
Technical field
The invention belongs to the biological medicine technology field, be specifically related to 3, the application of 3`-di-indole methyl hydride in the treatment inflammatory bowel.
Background technology
Inflammatory bowel is common digestive tract disease, is to be inflammation mainly to involve the chronic non-special of rectum, colon, and its symptom mainly comprises stomachache, diarrhoea, hemafecia, and course of disease protracted course of disease, even has the canceration maybe.Treatment mainly concentrates on salicylic acid preparation, glucocorticoid, immunosuppressant etc. in the past to inflammatory bowel.But traditional treatment exists target spot still indeterminate, and side effect is bigger.Be prone to shortcomings such as recurrence after the drug withdrawal.
Though the pathogenesis of inflammatory bowel it be unclear that, research in recent years shows that free radical plays an important role in the generating process of enteritis.Free radical mainly comprises ultra-oxygen anion free radical (O
2 -), hydroxy radical (OH
-), hydrogen peroxide (H
2O
2) etc.In the inflammatory bowel generating process; The free-radical contents of inflammation part significantly raises; Its harm can destroy cellularity on the one hand, and the peroxidating of trigger cell membrane lipid produces catabolite malonaldehyde (MDA); Cause protein denaturation and crosslinked, directly cause function of intestinal canal imbalance and tissue injury.In addition on the one hand; Free radical can also pass through activating transcription factor NF-κ β; Induce the inflammation related gene expression, make the inflammatory factor level raise, the iuntercellular expression of adhesion molecule rises; Cause activated lymphocyte and mononuclear cell to move to inflammation part, further exacerbate inflammation property enteropathy patient's enteritis reaction by blood vessel.Be that target spot is treated the enteritis attack degree that can effectively reduce inflammation with the free radical for this reason.3,3 '-di-indole methyl hydride (DIM) and parent compound Indole-3-carbinol (I3C) thereof are in the news the earliest and have antitumaous effect.Indole-3-carbinol (I3C) is very unstable in the gastric acid environment in vivo, condensation reaction can take place form oligomer 3,3 '-di-indole methyl hydride.3, it can protect body to avoid radical damage though 3 '-di-indole methyl hydride has bibliographical information, does not have it to be used to treat the correlational study result report of inflammatory bowel as yet.
Summary of the invention
The problem that the present invention need solve discloses one type exactly and can effectively protect body to avoid radical damage; Thereby the small-molecule drug of blocking-up inflammatory bowel onste; Be specifically related to 3,3 '-di-indole methyl hydride (DIM) and aqueous solution ejection preparation thereof and the treatment of parent compound Indole-3-carbinol (I3C) in inflammatory bowel.
Involved in the present invention 3,3 '-di-indole methyl hydride and parent compound Indole-3-carbinol are the commercial gained (the sharp horse in Nanjing Fine Chemical Co., Ltd) of buying.
Involved in the present invention 3; 3 '-di-indole methyl hydride aqueous solution ejection preparation is to utilize cyclodextrin aqueous solution preparation gained; Concrete grammar is referring to patent of invention " application in treating rheumatoid arthritis of di-indole methyl hydride and derivant thereof " [Zhang Junfeng, Dong Lei, Xaisur China; Chen Jiangning, application number: 200810243556.8].
Of the present invention 3, the application in the inflammatory bowel treatment of 3 '-di-indole methyl hydride and parent compound Indole-3-carbinol:
1. 50% alcoholic solution that uses TNB (TNBS) is set up TNBS type inflammatory bowel disease model in the BALB/C mice coloclysis;
2. with 3,3 '-di-indole methyl hydride and Indole-3-carbinol are dissolved in the Semen Maydis oil, irritate stomach simultaneously setting up TNBS type inflammatory bowel disease model, and inflammatory bowel is treated;
3. the mice body weight is measured every day in the treatment back, and puts to death mice in treatment after 3 days, gets the pathological changes colon and takes pictures, and does Histological injury's scoring and MPO pH-value determination pH respectively.
Of the present invention 3, the application of the aqueous solution ejection preparation of 3 '-di-indole methyl hydride in the inflammatory bowel treatment:
1. 50% alcoholic solution that uses TNB (TNBS) is set up TNBS type inflammatory bowel disease model in the BALB/C mice coloclysis;
2. will prepare 3, the aqueous solution ejection preparation of 3 '-di-indole methyl hydride carries out lumbar injection simultaneously setting up TNBS type inflammatory bowel disease model, and inflammatory bowel is treated;
3. the mice body weight is measured every day in the treatment back, and puts to death mice in treatment after 3 days, gets the pathological changes colon and takes pictures, and does Histological injury's scoring and MPO pH-value determination pH respectively.
The invention has the beneficial effects as follows the method that a kind of new treatment inflammatory bowel is provided, through giving 3,3 '-di-indole methyl hydride and Indole-3-carbinol protection body are avoided radical damage, thus blocking-up and suppress the outbreak of enteritis.Simultaneously, small-molecule drug used in the present invention is easy to obtain, and is cheap, and stable in properties is convenient to storage and transport.
Description of drawings
Three days the histological score of I3C oral medication TNBS enteritis model of Fig. 1 various dose.
Three days colon MPO pH-value determination pH result of the oral I3C treatment TNBS enteritis model of Fig. 2.
Three days the histological score of DIM oral medication TNBS enteritis model of Fig. 3 various dose.
Three days colon MPO pH-value determination pH result of the oral DIM treatment TNBS enteritis model of Fig. 4.
Three days histological score of Fig. 5 DIM aqueous solution ejection preparation treatment TNBS enteritis model.
Three days colon MPO pH-value determination pH result of Fig. 6 lumbar injection DIM treatment TNBS enteritis model.
The specific embodiment
1. the treatment of the mice enteritis model that oral I3C causes TNBS
I3C is dissolved with Semen Maydis oil, and it is subsequent use to be made into the 2.0mg/ml liquid storage.Set up mice TNBS enteritis model according to the bibliographical information method; Promptly get 30 of female BALB/C mices; Body weight 16-18g, with TNBS solution (being dissolved in 50% ethanol) 0.1ml coloclysis, and modeling same day; It is I3C treatment low dose group, I3C treatment high dose group and negative control group that mice is divided into three groups at random, handles respectively.I3C treatment low dose group is pressed 4mg/kg and is irritated stomach to I3C, and I3C treatment high dose group is pressed 20mg/kg filling stomach and given I3C, and matched group is given the Semen Maydis oil of respective amount, and be administered once every day.Weighing every day mouse body weight.Modelling was put to death after 3 days, got pathological changes colon, did Histological injury's scoring and MPO pH-value determination pH.
(1) Histological injury's scoring
Get part colon and fix, carry out HE dyeing, do pathological section, microscopically is observed, and carries out Histological injury's scoring, and standards of grading are following:
Table one: colitis Histological injury standard
| |
0 | 1 | 2 | 3 |
| Epithelial damage and ulcer | Do not have | Rotten to the corn | Ulcer | Severe |
| The ulcer degree of depth | ? | Submucosa | The flesh layer | Placenta percreta |
| Edema | Do not have | Slightly | Moderate | Severe |
| Lymph, monokaryon, plasmocyte infiltrating | Do not have | Slightly | Moderate | Severe |
| Intramural invasion | ? | Submucosa | The flesh layer | Placenta percreta |
| Neutrophil infiltration | Do not have | Slightly | Moderate | Severe |
| Intramural invasion | ? | Submucosa | The flesh layer | Placenta percreta |
| The eosinophilic granulocyte is soaked into | Do not have | Slightly | Moderate | Severe |
| Intramural invasion | ? | Submucosa | The flesh layer | Placenta percreta |
(2) MPO determination of activity
Cut part pathological changes colon and weigh, per 200 mg add 1 ml, 0.2% HTAB, homogenate, freeze thawing 3 times, and 1 .083 * centrifugal 10 min gets 0.1 ml supernatant, is substrate with the dianisidine.Measure the average that 5 min internal absorbances change in wavelength 655 nm places with UV one 200 type ultraviolet spectrophotometers, it is 1 unit of enzyme activity that the per minute absorbance changes 1.0.
As can beappreciated from fig. 1 oral I3C can effectively be alleviated the mouse colitis outbreak, and colon's damage of treatment group is starkly lower than negative control group, and is certain dose dependent.The MPO value has been reacted the inflammatory cell infiltration degree in the tissue, also is a major criterion of measurement amount inflammation degree.The MPO value of as can beappreciated from fig. 2 treatment group obviously will be lower than negative control group.This shows that DIM can alleviate colon's damage and effectively reduce the inflammatory cell infiltration in the colon, thereby effectively controls the development of colitis, infringement palliates a disease
2. the treatment of the mice enteritis model that oral DIM causes TNBS
DIM is dissolved with Semen Maydis oil, and it is subsequent use to be made into the 2.0mg/ml liquid storage.The modelling of mice TNBS enteritis is with reference to implementing 1, and modeling same day, it is DIM treatment low dose group, DIM treatment high dose group and negative control group that mice is divided into three groups at random, handles respectively.DIM treatment low dose group is pressed 4mg/kg and is irritated stomach to DIM, and DIM treatment high dose group is pressed 20mg/kg filling stomach and given DIM, and matched group is given the Semen Maydis oil of respective amount, and be administered once every day.Weighing every day mouse body weight.Modelling was put to death after 3 days, got pathological changes colon, did Histological injury's scoring and MPO pH-value determination pH.Histological injury's scoring and MPO values determination method are seen embodiment 1.
As shown in Figure 3, the histological score of DIM treatment group is starkly lower than matched group, and its inflammatory cell infiltration degree of DIM treatment group as shown in Figure 4 is starkly lower than matched group, and oral in a word DIM can effectively be alleviated the mouse colitis outbreak.
3.DIM the treatment of the mice enteritis model that the aqueous solution ejection preparation causes TNBS
DIM is subsequent use with the liquid storage that cyclodextrin and normal saline are mixed with 1.0mg/kg.The modelling of mice TNBS enteritis is with reference to implementing 1, and modeling same day, it is DIM treatment low dose group, DIM treatment high dose group and negative control group that mice is divided into three groups at random, handles respectively.DIM treatment low dose group is pressed the 4mg/kg lumbar injection and is given DIM, and DIM treatment high dose group is pressed the 20mg/kg lumbar injection and given DIM, and matched group is given the normal saline of isodose, and be administered once every day.Weighing every day mouse body weight.Modelling was put to death after 3 days, got pathological changes colon, did Histological injury's scoring and MPO pH-value determination pH.Histological injury's scoring and MPO values determination method are seen enforcement 1.
Like Fig. 5 and shown in Figure 6, lumbar injection DIM aqueous solution preparation can alleviate mouse colitis inflammation degree equally.
Claims (1)
1.3, the application in preparation treatment inflammatory bowel medicine of 3`-di-indole methyl hydride and Indole-3-carbinol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105769407A CN102526030A (en) | 2010-12-07 | 2010-12-07 | Application of 3,3'-diindolylmethane in treating inflammatory bowel disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105769407A CN102526030A (en) | 2010-12-07 | 2010-12-07 | Application of 3,3'-diindolylmethane in treating inflammatory bowel disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102526030A true CN102526030A (en) | 2012-07-04 |
Family
ID=46334859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105769407A Pending CN102526030A (en) | 2010-12-07 | 2010-12-07 | Application of 3,3'-diindolylmethane in treating inflammatory bowel disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102526030A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108245509A (en) * | 2018-01-29 | 2018-07-06 | 南京大学 | The application of DIM and its derivative in preparing prevention chemotherapy and causing damage medicine |
| CN114984006A (en) * | 2022-06-13 | 2022-09-02 | 华中农业大学 | Application of 3,3' -diindolylmethane in preparation of medicine for treating feline infectious peritonitis |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003031409A1 (en) * | 2001-10-10 | 2003-04-17 | Cheil Jedang Corporation | 1h-indole derivatives as a highly selective cyclooxygenase-2 inhibitor |
| CN1686115A (en) * | 2005-04-06 | 2005-10-26 | 黄晶 | Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease |
| CN101138569A (en) * | 2007-08-31 | 2008-03-12 | 北京未名宝生物科技有限公司 | Pharmaceutical composition for improving curative effect of indole-3-methanol and derivant thereof |
| CN101428016A (en) * | 2008-12-23 | 2009-05-13 | 南京大学 | Uses of di-indole methyl hydride and its derivant in treating rheumatoid arthritis |
| CN101585800A (en) * | 2009-06-19 | 2009-11-25 | 中国科学院上海有机化学研究所 | Bis(indolyl)methane compound with bioactivity |
-
2010
- 2010-12-07 CN CN2010105769407A patent/CN102526030A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003031409A1 (en) * | 2001-10-10 | 2003-04-17 | Cheil Jedang Corporation | 1h-indole derivatives as a highly selective cyclooxygenase-2 inhibitor |
| CN1686115A (en) * | 2005-04-06 | 2005-10-26 | 黄晶 | Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease |
| CN101138569A (en) * | 2007-08-31 | 2008-03-12 | 北京未名宝生物科技有限公司 | Pharmaceutical composition for improving curative effect of indole-3-methanol and derivant thereof |
| CN101428016A (en) * | 2008-12-23 | 2009-05-13 | 南京大学 | Uses of di-indole methyl hydride and its derivant in treating rheumatoid arthritis |
| CN101585800A (en) * | 2009-06-19 | 2009-11-25 | 中国科学院上海有机化学研究所 | Bis(indolyl)methane compound with bioactivity |
Non-Patent Citations (1)
| Title |
|---|
| YOON HEE KIM,ET AL.: "3,3"-Diindolylmethane Attenuates Colonic Inflammation and Tumorigenesis in Mice", 《INFLAMM BOWEL DIS》, vol. 15, no. 8, 31 August 2009 (2009-08-31), pages 1164 - 1173 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108245509A (en) * | 2018-01-29 | 2018-07-06 | 南京大学 | The application of DIM and its derivative in preparing prevention chemotherapy and causing damage medicine |
| CN114984006A (en) * | 2022-06-13 | 2022-09-02 | 华中农业大学 | Application of 3,3' -diindolylmethane in preparation of medicine for treating feline infectious peritonitis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Deng et al. | Cordyceps cicadae mycelia ameliorate cisplatin‐induced acute kidney injury by suppressing the TLR4/NF‐κB/MAPK and activating the HO‐1/Nrf2 and Sirt‐1/AMPK pathways in mice | |
| Jagetia et al. | Acceleration of wound repair by curcumin in the excision wound of mice exposed to different doses of fractionated γ radiation | |
| Hou et al. | Glycyrrhizic acid prevents diabetic nephropathy by activating AMPK/SIRT1/PGC‐1α signaling in db/db mice | |
| Hussein et al. | Gelam honey inhibits the production of proinflammatory, mediators NO, PGE2, TNF‐α, and IL‐6 in carrageenan‐induced acute paw edema in rats | |
| CN105624126B (en) | Novel recombinant high-stability superoxide dismutase and application thereof | |
| Popov et al. | Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice | |
| CN105125610B (en) | Sunflower disk hydrolyzes application of the compound powder in preparing treatment or alleviating high lithemia gout disease drug | |
| Jiang et al. | Effects of extract from Mangifera indica leaf on monosodium urate crystal‐induced gouty arthritis in rats | |
| Wang et al. | Paeoniae radix alba polysaccharides obtained via optimized extraction treat experimental autoimmune hepatitis effectively | |
| Gao et al. | Saccharomyces boulardii Ameliorates Dextran Sulfate Sodium‐Induced Ulcerative Colitis in Mice by Regulating NF‐κB and Nrf2 Signaling Pathways | |
| Kanauchi et al. | Butyrate from bacterial fermentation of germinated barley foodstuff preserves intestinal barrier function in experimental colitis in the rat model | |
| Chang et al. | Preventive effects of velvet antler (Cervus elaphus) against lipopolysaccharide‐induced acute lung injury in mice by inhibiting MAPK/NF‐κB activation and inducing AMPK/Nrf2 pathways | |
| Fang et al. | Shuang‐Huang‐Lian Attenuates Lipopolysaccharide‐Induced Acute Lung Injury in Mice Involving Anti‐Inflammatory and Antioxidative Activities | |
| Han et al. | Zisheng Shenqi decoction ameliorates monosodium urate‐mediated gouty arthritis in rats via promotion of autophagy through the AMPK/mTOR signaling pathway | |
| Wang et al. | Intestinal anti-inflammatory effects of selenized Ulva pertusa polysaccharides in a dextran sulfate sodium-induced inflammatory bowel disease model | |
| Liang et al. | The protective effects of water extracts of compound turmeric recipe on acute alcoholism: An experimental research using a mouse model | |
| Li et al. | Baicalin Ameliorates DSS‐Induced Colitis by Protecting Goblet Cells through Activating NLRP6 Inflammasomes | |
| CN102526030A (en) | Application of 3,3'-diindolylmethane in treating inflammatory bowel disease | |
| Rovenský et al. | Treatment of rat adjuvant arthritis with flavonoid (detralex®), methotrexate, and their combination | |
| Bowers et al. | A comparative evaluation of particulate and soluble glucan in an endotoxin model | |
| Wang et al. | Effect of mussel polysaccharide on glucolipid metabolism and intestinal flora in type 2 diabetic mice | |
| Wang et al. | [Retracted] Intervention Study of Dictyophora Polysaccharides on Arsenic‐Induced Liver Fibrosis in SD Rats | |
| Shan et al. | Effect of an antidiabetic polysaccharide from Inula japonica on constipation in normal and two models of experimental constipated mice | |
| Xuan et al. | Targeting the programmed cell death (PCD) signaling mechanism with natural substances for the treatment of diabetic cardiomyopathy (DCM) | |
| CN107041880A (en) | Phosphodiesterase 4 inhibitors ZL-n-91 is preparing anti-lung cancer propagation and the application in diversion medicaments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120704 |
|
| WD01 | Invention patent application deemed withdrawn after publication |