CN113679733A - Compound for inhibiting colitis and application thereof - Google Patents
Compound for inhibiting colitis and application thereof Download PDFInfo
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- CN113679733A CN113679733A CN202111009396.2A CN202111009396A CN113679733A CN 113679733 A CN113679733 A CN 113679733A CN 202111009396 A CN202111009396 A CN 202111009396A CN 113679733 A CN113679733 A CN 113679733A
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- colitis
- monoglucoside
- hesperetin
- hesperetin monoglucoside
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- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 12
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- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims abstract description 31
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- AIONOLUJZLIMTK-AWEZNQCLSA-N hesperetin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-AWEZNQCLSA-N 0.000 claims abstract description 26
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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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
Abstract
The invention discloses a compound for inhibiting colitis and application thereof. Mainly comprises the application of hesperetin monoglucoside (Hes-7-G) in preventing/inhibiting/treating colitis. The hesperetin monoglucoside can prevent the intestinal length from being shortened due to the colitis, inhibit the metabolism of phosphorylcholine, betaine, glutamine and itaconic acid, and reduce the expression levels of inflammatory factors IL-1 beta, IL-6, IL-22 and TNF-alpha, so that the hesperetin monoglucoside can be further developed into a medicament for treating or preventing the colitis, and has wide application prospect. The hesperetin monoglucoside is taken as a known compound, is easy to obtain, low in cost and easy to popularize; the hesperetin monoglucoside has high sweetness, long lasting time, good stability and low calorie, does not influence the blood fat and blood sugar level of a human body, and can be used as a medicinal and edible product for preventing/inhibiting/treating colitis.
Description
Technical Field
The invention relates to the technical field of medical products, in particular to a compound for inhibiting colitis and application thereof.
Background
The human intestinal tract is considered a metabolic "super-organ" that possesses millions of microorganisms and genes that affect many physiological functions.
Colitis can be classified into infectious colitis, ischemic colitis, pseudomembranous colitis, ulcerative colitis and other types of inflammatory enteritis caused by biological factors, allergic reactions, physical and chemical factors and other factors according to the cause of disease.
Many studies have shown that most natural flavonoids have anti-inflammatory and antioxidant biological activities, including hesperidin. Hesperidin is a slightly bitter weakly acidic substance, and is mostly present in pulp and pericarp of citrus products such as sweet orange, naringin and lemon. Has antioxidant, free radical scavenging, antiinflammatory, antibacterial, antiviral, tranquilizing, and sleep improving effects. However, the hesperidin has low activity and can only take effect in a large dose, and meanwhile, the hesperidin has poor water solubility, is difficult to absorb by oral administration and has low bioavailability, so that the hesperidin is difficult to be used as a medicine for directly treating colitis.
Disclosure of Invention
The present invention aims to provide a compound for inhibiting colitis and the use thereof, which solves one or more of the technical problems in the prior art and provides at least one useful choice or creation condition.
The invention aims to provide application of hesperetin monoglucoside (Hes-7-G) in preventing/inhibiting/treating colitis. The inventor surprisingly found that hesperetin monoglucoside can treat colitis, probably because the molecular structure of hesperetin monoglucoside after one rhamnose is removed can be better absorbed and utilized in colon. The hesperetin monoglucoside has an inhibiting effect on the expression levels of inflammatory factors interleukin 1 beta (IL-1 beta), interleukin 6(IL-6), interleukin 22(IL-22) and tumor necrosis factor alpha (TNF-alpha) at the cellular and molecular level, so that the hesperetin monoglucoside can be further developed into a medicament or a health-care product for treating or preventing colitis, and has wide application prospect.
The hesperetin monoglucoside naturally exists in pulp and pericarp of citrus products such as pericarpium Citri Tangerinae, fructus Citri sinensis, naringin and fructus Citri Limoniae, but its content is low. The dosage concentration of the hesperetin monoglucoside preparation is 0.5-5mg/kg, and the dosage is difficult to reach by common food materials, so that tablets, capsules, granules, oral liquid, sustained-release preparations, controlled-release preparations, nano preparations and the like taking hesperetin monoglucoside as an active ingredient can be directly and well absorbed after reaching intestinal tracts and quickly take effect on inflammation.
In vitro/in vivo experiments prove that the feasibility of the hesperetin monoglucoside in preparing medicaments and health-care products for preventing/treating the colitis is realized.
In vitro experiments prove that the Hes-7-G has an inhibiting effect on the metabolism of phosphorylcholine, betaine, glutamine and itaconic acid by co-culturing RAW264.7 mouse macrophages with LPS and Hes-7-G. Real-time fluorescent quantitation pcr analysis for the reduction of interleukin 1 beta (IL-1 beta) expression levels.
The in vivo test shows that the expression level of inflammatory factors interleukin 1 beta (IL-1 beta), interleukin 6(IL-6), interleukin 22(IL-22) and tumor necrosis factor alpha (TNF-alpha) is obviously reduced by histopathological examination and real-time fluorescent quantitative pcr analysis.
The invention has the following beneficial effects:
1. the hesperetin monoglucoside is taken as a known compound, is easy to obtain, low in cost and easy to popularize;
2. the hesperetin monoglucoside has high sweetness, long lasting time, good stability and low calorie, does not influence the blood fat and blood sugar level of a human body, and can be used as a medicinal and edible product for preventing/inhibiting/treating colitis;
3. the hesperetin monoglucoside can prevent intestinal length shortening caused by colitis, inhibit metabolism of phosphorylcholine, betaine, glutamine and itaconic acid, and reduce expression levels of inflammatory factors interleukin 1 beta (IL-1 beta), interleukin 6(IL-6), interleukin 22(IL-22) and tumor necrosis factor alpha (TNF-alpha).
Drawings
FIG. 1 is the results for betaine, itaconic acid, phosphorylcholine and glutamine of example 1;
FIG. 2 shows the length of the colon and the results of the tissue section in example 1;
FIG. 3 is the results of the relative expression of interleukin 1. beta. at the cellular level of example 2;
FIG. 4 shows the results of the animal experiment of example 2 on the expression of IL-22;
FIG. 5 shows the results of the animal experiment of example 2 on the expression of IL-6, an inflammatory factor;
FIG. 6 shows the results of the animal experiment of example 2 on the expression of IL-1. beta. as an inflammatory factor;
FIG. 7 shows the results of the animal experiments of example 2 on the expression of TNF-. alpha.as an inflammatory factor.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to specific embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1, in vitro anti-inflammatory assay of hesperetin monoglucoside.
In vitro anti-inflammatory effects were studied by co-culturing hesperetin monoglucoside in vitro with RAW264.7 strain mouse macrophages. A blank control group, a Lipopolysaccharide (LPS) group and a treatment group (LPS + Hes-7-G) group were set up, respectively, each group had 6 parallel samples, and the cells were cultured in a 150mm petri dish. The blank control group is normally cultured for 12 hours; LPS (0.2. mu.g/ml) was added to the LPS group and cultured for 12 hours; the treatment group was incubated with LPS (0.2. mu.g/ml) and Hes-7-G (5. mu. mol/L) for 12 hours. After treatment, cells were harvested and washed twice with pbs buffer for later analysis. The metabolism of phosphorylcholine, betaine, glutamine and itaconic acid was analyzed by nuclear magnetic resonance hydrogen spectroscopy (1H-NMR) metabonomics for each sample. The expression level of interleukin 1 beta (IL-1 beta) was analyzed by real-time fluorescent quantitation pcr.
1H-NMR analysis found that the LPS group resulted in significantly elevated levels of itaconic acid and phosphorylcholine and reduced levels of betaine and glutamate. The treatment group restored cellular levels of phosphorylcholine, betaine and glutamine, but still increased levels of itaconic acid compared to the LPS group (as shown in figure 1). They are generally considered to be metabolic markers involved in cellular inflammation, structural components and energy metabolism, respectively. In addition, real-time fluorescent quantitation pcr analysis showed that the mRNA level of RAW264.7 cells Il-1 β was higher in the LPS group than in the treatment group (as shown in fig. 2). These observations indicate that Hes-7-G inhibits the effects of inflammation while simultaneously repairing the cell membrane structure, osmotic pressure and energy metabolism disrupted by LPS treatment in macrophages.
Example 2, Hes-7-G in vivo anti-inflammatory assay.
The animal experiment procedure was performed according to the national guidelines of China and approved by the animal ethics Committee of the institute of precision measurement science and technology Innovation (the national academy of sciences). There were 24 female c57bl/6n mice (16-18g body weight) 6 weeks old, housed in a pathogen-free animal chamber, thermostated and humidified, 12 hours light/dark cycle. After 1 week of acclimation to the conditions, the mice were randomly divided into a control group, a DDS group, and a treatment group, each group consisting of 8 mice. Control group: the purified water is freely drunk and the purified water is used for gastric perfusion for 7 days. DDS group: 1.5% DSS (sodium dextran sulfate) was drunk freely for 7 days. Treatment groups: 1.5% DSS was drunk freely and gavage with Hes-7-G (1mg/ml) for 7 days. At the end of the treatment period, plasma, liver, colon and cecal contents were collected from mice immediately after 8 hours fasting post isoflurane anesthesia. All samples collected were stored at-80 ℃. After colon length measurement, a portion of the colon tissue was fixed in 10% formalin for histopathological examination, and the remainder was stored at-80 ℃ until analysis. The real-time fluorescence quantitative pcr analyzes the expression level of inflammatory factors interleukin 1 beta (IL-1 beta), interleukin 6(IL-6), interleukin 22(IL-22) and tumor necrosis factor alpha (TNF-alpha).
Hes-7-G significantly reduced the extent of tissue damage, as shown in FIG. 3A: in the figure, (a) reduces mucosal lining disorganization, (b) reduces inflammatory cell infiltration, (c) reduces connective tissue proliferation and inhibits cell necrosis; significantly inhibit colon length shortening in mice (see fig. 3B, fig. 3C); significantly reduces the inflammatory state of colon, and shows that the mRNA level of inflammatory cytokines TNF-alpha, IL-22, IL-1 beta and IL-6 is significantly reduced (as shown in figure 4, figure 5, figure 6 and figure 7). Indicating that the Hes-7-G can effectively prevent the colon from shortening and inhibit the inflammation level of the colitis.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Claims (7)
1. Application of hesperetin monoglucoside in preventing/inhibiting/treating colitis is provided.
2. Application of hesperetin monoglucoside in preparation of medicine and health product for preventing/treating colitis is provided.
3. The use according to claim 2, characterized in that hesperetin monoglucoside is used as an active ingredient to be prepared into tablets, capsules, granules, oral liquids, sustained release preparations, controlled release preparations, nano preparations, injections and any pharmaceutically acceptable dosage forms.
4. Use according to claim 2, characterized in that hesperetin monoglucoside inhibits the shortening of the colon length.
5. Use according to claim 2, characterized in that hesperetin monoglucoside inhibits the metabolism of phosphorylcholine, betaine, glutamine.
6. Use according to claim 2, characterized in that hesperetin monoglucoside inhibits the metabolism of the inflammatory cytokines TNF- α, IL-22, IL-1 β, IL-6.
7. The use according to claim 2, characterized in that the hesperetin monoglucoside has an action concentration of 0.5 to 5 mg/kg.
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