CN115475173A - Application of D-xylose in preparation of medicines for improving intestinal tract mucosa inflammation and resisting early diabetes - Google Patents
Application of D-xylose in preparation of medicines for improving intestinal tract mucosa inflammation and resisting early diabetes Download PDFInfo
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- CN115475173A CN115475173A CN202211352375.5A CN202211352375A CN115475173A CN 115475173 A CN115475173 A CN 115475173A CN 202211352375 A CN202211352375 A CN 202211352375A CN 115475173 A CN115475173 A CN 115475173A
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- Prior art keywords
- xylose
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- intestinal tract
- tract mucosa
- preparation
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- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 title claims abstract description 39
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- 201000010927 Mucositis Diseases 0.000 title claims abstract description 14
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- 239000003613 bile acid Substances 0.000 abstract description 15
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 abstract description 13
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The invention relates to application of D-xylose in preparing a medicament for improving intestinal tract mucosa inflammation and resisting early diabetes. The D-xylose can affect the relative abundance of key bacteria such as Christenseella, ruminococcus and Candidatus-Saccharomonas which are closely related to the metabolic pathway of bile acid, and can affect the pathway of bile acid, inhibit inflammatory factors, protect intestinal mucosa and relieve early insulin resistance.
Description
Technical Field
The invention belongs to the technical field of sugar alcohol application, and particularly relates to application of D-xylose in preparation of a medicament for improving intestinal tract mucosa inflammation and resisting early diabetes.
Background
The efficacy of the existing D-xylose comprises the following two aspects:
(1) D-xylose can regulate blood sugar level through a key rate-limiting enzyme PEPCK in the processes of regeneration of damaged pancreas and liver tissues and regulation of gluconeogenesis, thereby playing an anti-diabetic role in vivo. In vitro, D-xylose induces glucose uptake by muscle cells and insulin secretion by β -cells (PMID: 26865911).
(2) D-xylose may be useful in preventing or slowing obesity by affecting the adipogenic gene SREBP-1c, fatty acid synthase, CCAAT/enhancer binding protein alpha, etc. proteins to reduce adipogenesis and dyslipidemia and to improve lipid oxidation. (PMID: 26088373).
Therefore, the main effects of the existing D-xylose are focused on regulating key enzymes in the gluconeogenesis process, improving fasting blood glucose level through ways of inducing muscle cells to take glucose by insulin and the like, and inhibiting lipogenesis by influencing lipogenesis genes, improving diseases such as blood fat increase and obesity and the like. However, no report is available about the metabolic pathway of regulating intestinal flora by D-xylose.
Disclosure of Invention
The invention aims to solve the technical problem of providing the application of D-xylose in preparing a medicament for improving intestinal tract mucosa inflammation and resisting early diabetes, wherein the D-xylose passes through two paths: the method has the advantages that firstly, the sugar metabolism is improved by influencing the abundance of relevant bacteria in the bile acid metabolic pathway, secondly, the abundance of relevant bacteria for inhibiting inflammatory factors is improved, the intestinal mucosa inflammation is improved, and the early insulin resistance is relieved.
The invention is realized in such a way, and provides the application of D-xylose in preparing a medicament for improving intestinal mucosa inflammation.
The invention is realized in such a way, and provides the application of D-xylose in preparing the anti-early diabetes medicine.
The invention is realized in such a way, and provides the application of D-xylose in preparing health-care food for improving intestinal mucosa inflammation.
The invention is realized in such a way, and provides the application of D-xylose in preparing health-care food for resisting early diabetes.
It has been shown that oral administration of D-xylose can significantly increase the levels of ruminobacteria (Ruminococcaceae) and Cristenssen (Christensella) in the intestinal tract. The genus Christensella is considered as a key member of the intestinal microbiota and can regulate the energy balance and obesity of the host, and meanwhile, it has been shown that the genus Christensella has proteins having a bile salt hydrolase action therein, bile acid capable of being preferentially uncoupled from glycine (PMID: 34207623), and bound bile acid is converted into free bile acid by the action of bile salt hydrolase and further into deoxycholic acid and lithocholic acid by 7 α -dehydroxylation by the action of genus Ruminococcus (PMID: 32101703). The secondary bile acids deoxycholic and lithocholic acids are the most abundant metabolites of the gut microbiome, regulating host energy homeostasis and metabolism via the G-protein coupled receptor TGR5 (PMID: 24411485). Bile acids can also control the production of glucagon-like peptide-1 (GLP-1) by acting on FXR. The bile acid chelating agent colesevelam stimulates secretion of GLP-1 in ob/ob mice depending on an FXR signal pathway to improve blood sugar, and the FXR/GLP-1 pathway is proved to be a new mechanism for controlling carbohydrate metabolism by bile acid and also to be a pharmacological target of early diabetes (type 2 diabetes) (PMID: 26134028).
D-xylose-dry prognosis, up-regulated expression of Christenseella, CS (Candidatus _ Saccharioninas), closely related to lower levels of inflammation, prevention of obesity, etc. (PMID: 31324278). There are studies showing that metformin dry prognosis, christensella levels are also increased, the latter being shown to correlate well with low body mass index in twin experiments (PMID: 31445961). Studies have shown that egg white peptide can reduce the levels of proinflammatory cytokines (tumor necrosis factor (TNF-. Alpha.), interleukin-1. Beta. (IL-1. Beta.), interleukin-6 (IL-6) and interleukin-8 (IL-8)) and the degree of crypt damage in a dose-dependent manner in a mouse model of Dextran Sodium Sulfate (DSS) -induced colitis and significantly increase the relative abundance of beneficial bacteria Lactobacillus and Candidatus Saccharionias, and is negatively correlated with the level of inflammatory factors (PMID: 34020366). After the D-xylose is dried, the inflammatory reaction of the intestinal tract of a mouse is improved, epithelial cells of a mucous layer drop less, the number of intestinal glands of an inherent layer is rich, goblet cells are more, and inflammatory reactions such as lymphocyte infiltration and the like are not seen, so that the D-xylose can play a role in protecting the intestinal tract mucosa and improving the insulin resistance of type 2 diabetes (early diabetes) through the bile acid pathway of intestinal flora and the inhibition of the inflammatory reaction.
Drawings
FIG. 1 is a schematic diagram of intestinal tissue sections of mice in an animal intervention experiment negative control group, a model control group and a D-xylose intervention group.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The invention discloses application of D-xylose in preparation of a medicament for improving intestinal tract mucosa inflammation and resisting early diabetes.
The invention also discloses application of the D-xylose in preparing health-care food for improving intestinal tract mucosa inflammation.
The invention also discloses application of the D-xylose in preparing health-care food for improving intestinal tract mucosa inflammation.
Specifically, the health food is a beverage or a dietary supplement.
Experiments are used for further verifying the effects of the D-xylose in preparing the medicines for improving intestinal tract mucosa inflammation and resisting early diabetes.
1. Animal intervention experiment
The male C57BL/6J mice were randomly divided into 3 groups of 10 mice each, and the mice fed with normal diet were used as a negative control group (basal diet + distilled water 0.1mL/kg · bw, BC group), the high-fat feeding group was used as a model control group (high-fat diet + distilled water 0.1mL/kg · bw, MC group), and a D-xylose-dried group (high-fat diet + D-xylose 75mg/kg · bw, DM group). Each group of mice was administered by intragastric administration 1 time a day, and during the experiment, the mice had free access to water. Mice were intervened for 14 weeks altogether, and OGTT (glucose tolerance), ITT (insulin tolerance) assays were performed at week 12, and fasting plasma glucose, fasting serum insulin, and 16S rRNA intestinal microbial sequencing and colon tissue sections and HE staining were performed at week 14.
2. Index detection
(21) Biochemical and immunological index detection: indexes such as fasting plasma glucose (FBG, hexokinase method) and fasting serum insulin (FINS, latex immunoturbidimetry) were measured according to the kit instructions, and all the kits were purchased from Zhongsheng North-China Biotechnology Ltd. The blood glucose measurements at the time points of the OGTT and ITT were performed using a glucometer and test strips purchased from roche.
(22) Sequencing intestinal microorganisms: bacterial genomes in intestinal contents of mice were extracted using a bacterial DNA extraction kit (DP 302) and samples with a DNA concentration of 20 ng/. Mu.L were selected for further PCR amplification. The genome was amplified by PCR to obtain V4-V5 regions of the bacterial 16S rRNA gene. Amplicons were gel recovered after 2% agarose gel electrophoresis, purified using a gel extraction kit according to manufacturer's instructions, and quantified. The purified amplicons were pooled in an equimolecular sequencing pool and subjected to paired sequencing. The original file is quality filtered. Sequences with 97% similarity were clustered into one operational unit (OTUs) and chimeric sequences were identified and removed. And analyzing and annotating development genetic relationship by using an RDP classifier.
(23) Colon tissue section:
colon tissue was prepared as follows: fixation → dehydration → embedding → sectioning → deparaffinization → HE staining → dehydration transparency → mounting, and 5 fields of view were randomly selected for each tissue to be photographed under a microscope.
3. Results of the experiment
(31) Biochemical index results: the fasting blood glucose of the mice is detected, compared with a negative control group, after the mice are fed with high-fat feed, the fasting blood glucose is increased from 7.80 +/-0.87 mmol/L to 12.17 +/-1.25 mmol/L, the difference is obvious (p is less than 0.001), after the D-xylose is dried, the fasting blood glucose is obviously lower than that of a model control group, and is reduced from 12.17 +/-1.25 mmol/L to 9.81 +/-1.27 mmol/L (p is less than 0.001); in the early stage of diabetes, insulin levels increase, i.e., hyperinsulinemia occurs, insulin sensitivity decreases, and insulin resistance occurs (PMID: 32819363). And the use of D-xylose intervention can significantly reduce the insulin level, and the serum insulin is reduced from 10.19 +/-0.76 to 7.29 +/-2.72 ng/mL (p is less than 0.01), thereby relieving early insulin resistance caused by high fat diet. In the oral glucose tolerance test, the peak blood glucose values were significantly elevated and the area under the curve was significantly increased after induction with high fat diet (1390 ± 71vs.2134 ± 196, p-straw 0.001), whereas D-xylose intervention was effective in lowering the peak value of the curve and decreasing the area under the curve (p < 0.001). In the insulin tolerance test, D-xylose intervention significantly improved insulin tolerance compared to the model group (p < 0.001).
The results were as follows:
note: compared to the model control group, indicates a significance index p <0.05, indicates a significance index p <0.01, and indicates a significance index p <0.001.
(32) Sequencing results of intestinal microorganisms
The relative abundance of the genera christensella, ruminococcaceae, and Candidatus _ saccharas, which are closely related to the bile acid metabolic pathway, was examined, and it was found that the relative abundance of the genera christensella, ruminococcaceae, and Candidatus _ saccharas, which are closely related to the bile acid metabolic pathway, was significantly increased in the DM group compared to the BC group and the MC group for the D-xylose drying prognosis.
(33) Tissue section staining
Referring to fig. 1, the negative control group (BC group) mice had clear colonic plica folds, intact mucosal intestinal epithelium, and a single-layered columnar epithelium with normal epithelial cell morphology and abundant intestinal glands in the lamina propria, and showed more goblet cells and no obvious inflammatory reaction. The mucosal layer of mice in the high lipid model group (MC group) was seen with more epithelial cell detachment (as indicated by arrow 1), disappearance of intestinal glands and hyperplastic connective tissue replacement (as indicated by arrow 2) in the lamina propria, and individual mice were accompanied with punctate infiltration of lymphocytes (as indicated by arrow 3). The intestinal inflammation reaction of the D-xylose intervention group (DM group) mice is improved, the epithelial cells of the mucosa layer are less shed, the number of the intestinal glands of the lamina propria is rich, the goblet cells are more, and the inflammatory reaction such as lymphocyte infiltration is not seen.
Therefore, D-xylose can affect the bile acid pathway and inhibit inflammatory factors by influencing the relative abundance of key bacteria such as Christensella, ruminococcus and Candidatus-Saccharomonas which are closely related to the bile acid metabolic pathway, thereby protecting the intestinal mucosa and relieving early insulin resistance.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (6)
1. An application of D-xylose in preparing medicine for improving intestinal tract mucosa inflammation is disclosed.
2. An application of D-xylose in preparing medicine for preventing early diabetes is disclosed.
3. An application of D-xylose in preparing health food for improving intestinal tract mucosa inflammation is provided.
4. Use of D-xylose according to claim 3 for the preparation of a nutraceutical for the improvement of intestinal mucosal inflammation, characterized in that it is a drink or a dietary supplement.
5. An application of D-xylose in preparing health food for preventing early diabetes is provided.
6. Use of D-xylose according to claim 5 for the preparation of an anti-prediabetes, characterized by the fact that said health food is a drink or a dietary supplement.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107669691A (en) * | 2017-11-24 | 2018-02-09 | 天津医科大学 | Monose wood sugar product is preparing the application in preventing and treating urinary system infection contamination medicine |
| CN108653298A (en) * | 2018-06-13 | 2018-10-16 | 中国人民解放军第四军医大学 | Monosaccharide composition, pharmaceutical preparation and its application |
| US20200345795A1 (en) * | 2017-11-01 | 2020-11-05 | Medlab Ip Pty Ltd | Modulation of intestinal microbiota in pre-diabetes and type 2 diabetes |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200345795A1 (en) * | 2017-11-01 | 2020-11-05 | Medlab Ip Pty Ltd | Modulation of intestinal microbiota in pre-diabetes and type 2 diabetes |
| CN107669691A (en) * | 2017-11-24 | 2018-02-09 | 天津医科大学 | Monose wood sugar product is preparing the application in preventing and treating urinary system infection contamination medicine |
| CN108653298A (en) * | 2018-06-13 | 2018-10-16 | 中国人民解放军第四军医大学 | Monosaccharide composition, pharmaceutical preparation and its application |
Non-Patent Citations (2)
| Title |
|---|
| EUNJU KIM等: "D-Xylose as a sugar complement regulates blood glucose levels by suppressing phosphoenolpyruvate carboxylase (PEPCK) in streptozotocin-nicotinamide-induced diabetic rats and by enhancing glucose uptake in vitro", 《NUTRITION RESEARCH AND PRACTICE》, vol. 10, no. 1, pages 275 - 279 * |
| 盛老: "D-木糖", pages 1 - 3, Retrieved from the Internet <URL:www.360doc.com> * |
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