Application of clinopodium polycephalum saponin in preparation of medicine or functional food for preventing and / or treating digestive tract inflammation

Abstract

The invention relates to an application of clinopodium polycephalum saponin in preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation. In the prior art, although anti-inflammatory drugs such as aminosalicylic acid, glucocorticoid and the like can relieve inflammation symptoms, the cure rate is low, many adverse reactions are caused, and drug resistance or liver and kidney toxicity can be caused by long-term use of the anti-inflammatory drugs. According to the invention, clinopodium polycephalum saponin is innovatively used as an active component, so that the defects in the prior art are overcome. The clinopodium polycephalum saponin remarkably improves pathological damage and iron metabolism imbalance in colon tissue by regulating and controlling iron metabolism of a body and reducing inflammatory factor levels (such as TNF-alpha, IL-1 and IL-6). Experimental results show that clinopodium polycephalum saponin can effectively relieve symptoms in a DSS-induced mouse ulcerative colitis model, and the symptoms comprise the problems of weight loss, colon shortening, inflammatory factor rising, Fe < 2 + > level abnormity and the like.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to the application of phlomis saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation. Background Art

[0002] Digestive tract inflammation is a common chronic inflammatory disease in clinical practice, and its treatment usually relies on anti-inflammatory drugs. In the prior art, aminosalicylic acid, glucocorticoids, and antibacterial drugs are the main drugs for treating digestive tract inflammation. These drugs relieve inflammatory symptoms by inhibiting the release of inflammatory factors or regulating immune responses. However, the cure rate of existing drugs is relatively low, and long-term use may lead to problems such as drug resistance and adverse reactions, making it difficult to meet clinical needs.

[0003] The basic structure of existing anti-inflammatory drugs usually includes an active ingredient and a pharmaceutically acceptable excipient, and is administered in dosage forms such as tablets and capsules. Although these drugs can relieve inflammatory symptoms in the short term, their mechanism of action mainly focuses on inhibiting the release of inflammatory factors, without involving an innovative path for regulating the body's iron metabolism. In addition, the existing drugs have limited regulation on the level of divalent iron in colon tissues and cannot fundamentally improve the pathological mechanism of digestive tract inflammation. Therefore, there are significant deficiencies in the efficacy, safety, and long-term use effects of the prior art, and there is an urgent need to develop a new anti-inflammatory drug with definite efficacy and low toxicity and side effects. Summary of the Invention

[0004] In order to make up for the deficiencies of the prior art, the embodiments of the present application provide the application of phlomis saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation, solve the problems of low cure rate and many adverse reactions of anti-inflammatory drugs in the prior art, and achieve an efficient and safe treatment effect by regulating iron metabolism and reducing the level of inflammatory factors.

[0005] In order to solve the above technical problems, the present invention provides the following technical solution: An application of phlomis saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation, the application comprising the following steps:

[0006] Combining the phlomis saponins with a pharmaceutically or foodologically acceptable excipient to prepare a drug or a functional food;

[0007] Administering the drug or the functional food through an oral or injection route;

[0008] By regulating the body's iron metabolism, inhibiting the release of inflammatory factors TNF-α, IL-1β, and IL-6, thereby alleviating the symptoms of digestive tract inflammation.

[0009] Preferably: The digestive tract inflammation is ulcerative colitis, Crohn's disease, gastritis, enteritis, or duodenitis.

[0010] Preferably, the dosage form of the drug is tablet, capsule, granule, or oral liquid; the tablet contains one or more excipients selected from starch, dextrin, maltodextrin, and sodium carboxymethylcellulose.

[0011] Preferably, the functional food is a health food, a nutritional supplement, or a food for special medical purposes.

[0012] Preferably, the preparation method of the drug or functional food includes: mixing the phlomis umbrosa saponins with excipients and then pressing them into tablets, or dispersing them in a 0.5% sodium carboxymethylcellulose solution to prepare an oral liquid.

[0013] Preferably, the regulation of iron metabolism specifically refers to reducing the level of divalent iron in the colon tissue.

[0014] Preferably, the alleviation of digestive tract inflammatory symptoms includes at least one of improving the shortening of the colon length, inhibiting the destruction of the crypt structure, and reducing the infiltration of inflammatory cells.

[0015] One or more technical solutions provided in the embodiments of the present application have at least the following technical effects or advantages:

[0016] By providing the application of phlomis umbrosa saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation, the present invention solves the problems of low cure rate and many adverse reactions of anti-inflammatory drugs in the prior art. Using phlomis umbrosa saponins as the active ingredient, the present invention significantly improves the pathological damage and iron metabolism imbalance in the colon tissue by regulating the body's iron metabolism and reducing the level of inflammatory factors. Experimental results show that phlomis umbrosa saponins can effectively relieve the symptoms in a mouse ulcerative colitis model induced by DSS, including weight loss, colon shortening, elevated inflammatory factors, and abnormal Fe2+ levels, etc. Moreover, its curative effect is equivalent to or even better than that of existing drugs, and it has higher safety and lower toxicity and side effects. By innovatively combining the regulation of iron metabolism and the anti-inflammatory mechanism, the present invention provides a new solution for the prevention and treatment of digestive tract inflammation.

[0017] Other advantages, objectives, and features of the present invention will be elaborated to some extent in the subsequent description, and to some extent, they will be obvious to those skilled in the art based on the study of the following text, or can be taught from the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a schematic structural diagram of phlomis umbrosa saponins for the application of phlomis umbrosa saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation according to the present invention;

[0019] Figure 2The changes in body weight gain rate, colon length, colon morphology, DAI score, and food intake of mice induced by DSS by the Clinopodium polycephalum saponins for the application of the Clinopodium polycephalum saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation;

[0020] Figure 3 The effects of the Clinopodium polycephalum saponins for the application of the Clinopodium polycephalum saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation on the levels of inflammatory factors TNF-α, IL-1, IL-6 in the serum of mice induced by DSS, and the pathological levels of the colon and spleen of mice;

[0021] Figure 4 The effect of the Clinopodium polycephalum saponins for the application of the Clinopodium polycephalum saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation on the level of divalent iron in the colon tissue of mice induced by DSS. Detailed implementation manners

[0022] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0023] It should be noted that the terms "vertical", "horizontal", "upper", "lower", "left", "right" and similar expressions used herein are only for the purpose of illustration and do not represent the only implementation manner.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs; the terms used in the description of the present invention in this specification are only for the purpose of describing specific implementation manners and are not intended to limit the present invention; the term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0025] The present invention provides an innovative application of Clinopodium polycephalum saponins in the preparation of drugs or functional foods for preventing and / or treating digestive tract inflammation. The core of its technology lies in:

[0026] New use and mechanism breakthrough: For the first time, it is revealed that Clinopodium polycephalum saponins improve digestive tract inflammation through the dual pathways of regulating iron metabolism and inhibiting inflammatory factors, which is different from the direct action mechanism of traditional anti-inflammatory drugs and avoids the problem of drug resistance.

[0027] Clear curative effect: Animal experiments show that oral administration of Clinopodium polycephalum saponins can restore colon shortening induced by DSS.

[0028] Diversified dosage forms: It can be made into tablets, oral liquids or functional foods to adapt to different application scenarios.

[0029] Based on the above scheme, in one or more feasible embodiments:

[0030] Example 1: The effect of Clinopodium polycephalum saponins on a DSS-induced ulcerative colitis mouse model.

[0031] Experimental animals: C57BL / 6 mice, 6 - 8 weeks old, male.

[0032] Drug preparation: Clinopodium polycephalum saponins with dosages of 10 mg / tablet and 40 mg / tablet for preparing tablets for preventing and treating ulcerative colitis were ultrasonically dispersed in 0.5% sodium carboxymethylcellulose for gavage administration to mice, and the administration doses were 10 mg / Kg and 40 mg / Kg.

[0033] Experimental method:

[0034] Animal grouping: After one week of adaptive feeding of the mice, the mice were divided into a control group, a model group, a low-dose group, a high-dose group and a mesalazine group, with 8 - 12 mice in each group.

[0035] Drug administration: The low-dose group and the high-dose group were respectively gavaged with 10 mg / Kg and 40 mg / Kg per day; the control group and the model group were respectively gavaged with an equal volume of 0.5% CMC-Na per day; the mesalazine group was gavaged with 200 mg / Kg of mesalazine per day. The administration was continued for 21 days.

[0036] Model establishment: 14 days after drug administration, the mice in the model group, the low-dose group, the high-dose group and the mesalazine group were allowed to freely drink 3% DSS solution to induce an ulcerative colitis mouse model, and the mice in the control group drank pure water. The model establishment was continued for 1 week.

[0037] Recording: During the model establishment period, the body weight, daily food and water intake of the mice were recorded, and the fecal conditions of the mice were observed. The fecal occult blood test paper was used to detect the fecal occult blood condition.

[0038] Sampling: On the 21st day of drug administration, blood was collected by eye socket puncture, and then the mice were anesthetized and sacrificed. The heart, liver, spleen, lung, kidney and colon tissues of the mice were taken. The colon tissues were photographed, and the lengths were measured. The terminal 2 cm of the colon tissues were respectively fixed in 4% paraformaldehyde solution for subsequent HE staining. The remaining parts were frozen at -80 °C for subsequent detection.

[0039] 4. Experimental results

[0040] As shown in the appendix Figure 1 The structural formula of Clinopodium polycephalum saponins

[0041] As shown in the appendix Figure 2As shown: Compared with the control group, the length of the colon in the model group was significantly shortened, and the low-dose and high-dose groups of Clinopodium polycephalum saponins could alleviate DSS-induced colon shortening. The effect of the low-dose group was more obvious than that of the high-dose group, and it was similar to the effect of mesalazine.

[0042] As shown in the appendix Figure 3 As shown: ELISA experiments showed that the inflammatory factors in the serum of mice in the model group were significantly increased, while the inflammatory level in the treatment group decreased. This indicated that Clinopodium polycephalum saponins could reduce the inflammatory level of DSS-induced UC mice. At the same time, HE staining showed that compared with the control group, there were crypt deformities and inflammatory infiltrations in the colon of mice in the model group, indicating that the mouse barrier was severely damaged and the UC model was successfully established. After treatment with Clinopodium polycephalum saponins and mesalazine, the colon injury of mice was recovered and the degree of the lesion was alleviated. It was suggested that Clinopodium polycephalum saponins had an obvious improvement effect on DSS-induced UC.

[0043] As shown in the appendix Figure 4 As shown: Take the frozen mouse colon tissue, add normal saline, grind it, and take an appropriate amount to detect the Fe 2+ level according to the kit instruction manual. The results showed that compared with the control group, the Fe 2+ level in the model group was significantly increased, which was consistent with the previous reports. Compared with the model group, the Fe 2+ level in the Clinopodium polycephalum saponins group and the mesalazine group was significantly decreased, indicating that Clinopodium polycephalum saponins could improve DSS-induced colitis by regulating iron metabolism.

[0044] In the above-mentioned scheme, in the prior art, Clinopodium polycephalum saponins were mainly used for hemostasis and clearing heat and detoxifying, but their application in digestive tract inflammation was not involved. The present invention for the first time confirmed through experiments that it improved digestive tract inflammation through the dual mechanisms of regulating iron metabolism and inhibiting the release of inflammatory factors, filling the technical gap.

[0045] Traditional therapeutic drugs directly inhibit the inflammatory response, but the present invention proposes to indirectly regulate the inflammatory pathway by regulating iron metabolism, avoiding the problem of drug resistance in long-term medication, and having significant mechanism innovation.

[0046] Advantages of technical effects

[0047] Clear curative effect: Example 1 showed that Clinopodium polycephalum saponins could significantly restore DSS-induced colon shortening, and the effect was equivalent to that of mesalazine, but the dose was lower and the risk of side effects was smaller.

[0048] Multi-target regulation: It was confirmed by ELISA detection that the levels of TNF-α and IL-6 in the serum of mice in the Clinopodium polycephalum saponins group decreased compared with the model group, and the Fe2+ level in the colon decreased.

[0049] Although the present invention has been disclosed above in its preferred embodiments, it is not intended to limit the present invention. Anyone skilled in this technology can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention should be defined by the claims.

Claims

1. An application of a saponin for the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The application comprises the following steps: (1) combining the blood-breaking saponin with pharmaceutically or food-acceptable excipients to prepare a medicine or functional food; (2) administering the drug or functional food orally or by injection; (3) By regulating the body's iron metabolism, it inhibits the release of inflammatory factors TNF-α, IL-1β, and IL-6, thereby alleviating the symptoms of gastrointestinal inflammation.

2. The use of a saponin according to claim 1 in the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The digestive tract inflammation is ulcerative colitis, Crohn's disease, gastritis, enteritis or duodenitis.

3. The use of a saponin according to claim 1 in the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The dosage form of the drug is tablets, capsules, granules, and oral liquid; the tablets contain one or more auxiliary materials selected from starch, dextrin, maltodextrin, and sodium carboxymethyl cellulose.

4. The use of a saponin according to claim 1 in the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The functional food is a health food, a nutritional supplement or a special medical purpose formula food.

5. The use of a saponin according to claim 1 in the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The preparation method of the medicine or functional food comprises: mixing the diaoxilius saponin with auxiliary materials and pressing the mixture into tablets, or dispersing the mixture into a 0.5% sodium carboxymethyl cellulose solution to prepare an oral solution.

6. The use of a saponin according to claim 1 in the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The regulation of iron metabolism specifically refers to reducing the level of divalent iron (Fe2+) in colon tissue.

7. The use of a saponin according to claim 1 in the preparation of a medicine or functional food for preventing and / or treating digestive tract inflammation, characterized in that: The alleviation of digestive tract inflammation symptoms includes at least one of improving shortening of colon length, inhibiting crypt structure destruction, and reducing inflammatory cell infiltration.

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