Use of alnusenone in the preparation of a drug for preventing and / or treating ulcerative colitis

Abstract

The application provides application of alnus ketone in preparation of a medicine for preventing and / or treating ulcerative colitis, and belongs to the technical field of traditional Chinese medicines. The application research finds that alnus ketone can significantly reduce secretion of intestinal epithelial cell inflammatory factor IL-8, and has an anti-inflammatory effect. Animal experiments show that alnus ketone can reduce weight loss of mice caused by ulcerative colitis, reduce severity of occult blood, and reduce shortening of the colon, indicating that alnus ketone has a protective effect on ulcerative colitis. The alnus ketone is applied to clinical treatment, and has the advantages of high efficiency, low toxicity, economy and feasibility.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and in particular relates to the application of alder ketone in the preparation of drugs for the prevention and / or treatment of ulcerative colitis. Background Technology

[0002] Currently, commonly used drugs for the clinical treatment of ulcerative colitis (UC) mainly include aminosalicylic acids, immunosuppressants, steroids, and some biological agents. These drugs can alleviate the condition to some extent. However, at present, these drugs cannot completely repair the mucosal barrier function, and the efficacy is not satisfactory. Moreover, they are usually expensive, and long-term maintenance of medication will consume a lot of medical resources and cause many adverse reactions.

[0003] While aminosalicylic acid derivatives (such as mesalazine) are the first-line drugs, their efficacy is limited in moderate to severe cases. In some patients, differences in gut microbiota metabolism or uneven drug distribution lead to insufficient local concentrations, affecting efficacy. Long-term use of glucocorticoids easily causes side effects such as osteoporosis and metabolic disorders, and some patients develop "steroid resistance" or dependence, resulting in a high relapse rate after discontinuation. Immunosuppressants such as azathioprine and cyclosporine may cause bone marrow suppression, liver and kidney toxicity, and opportunistic infections. Furthermore, biologics are expensive and require long-term use, increasing the financial burden on patients.

[0004] For ulcerative colitis (UC), a chronic and relapsing refractory disease, traditional Chinese medicine (TCM) treatment has significant advantages in regulating overall bodily functions and reducing recurrence rates. Currently, there is an urgent clinical need for novel TCM preparations that are effective, safe, and cost-effective. This is of dual value in improving patients' quality of life, reducing the medical burden, and promoting the modernization of TCM. Therefore, finding and developing TCMs with good efficacy, few side effects, high safety, and low cost is not only important for UC patients but also beneficial to the development and progress of TCM. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide the application of alder ketone in the preparation of medicaments for the prevention and / or treatment of ulcerative colitis. This invention has found that alder ketone is a traditional Chinese medicine ingredient that is widely available, inexpensive, has few toxic side effects with long-term use, and can effectively treat ulcerative colitis.

[0006] This invention provides the use of alder ketone in the preparation of medicaments for the prevention and / or treatment of ulcerative colitis.

[0007] Preferably, the dosage of alder ketone is 10-50 mg / kg.

[0008] Preferably, the alder ketone can alleviate weight loss, occult blood, and colonic shortening caused by ulcerative colitis.

[0009] This invention provides the application of alder ketone in the preparation of reagents that inhibit the expression of inflammatory factors in human colon adenocarcinoma cell lines.

[0010] Preferably, the human colon adenocarcinoma cell line is the HT-29 cell line.

[0011] Preferably, the inflammatory factor is IL-8.

[0012] Preferably, the concentration of alder ketone used is 5–50 μg / mL.

[0013] Compared with existing technologies, this invention has the following beneficial effects: This invention provides the application of alder ketone in the preparation of drugs for the prevention and / or treatment of ulcerative colitis. This invention's research found that alder ketone can significantly reduce the secretion of the inflammatory factor IL-8 in intestinal epithelial cells, exhibiting an anti-inflammatory effect; animal experiments showed that alder ketone can reduce weight loss, reduce the severity of occult blood in mice caused by ulcerative colitis, and reduce colonic shortening, suggesting that alder ketone has a protective effect against ulcerative colitis. Applying alder ketone to clinical treatment has the advantages of high efficiency, low toxicity, and economic feasibility. Attached Figure Description

[0014] Figure 1 The effect of TNF-α stimulation on the expression of the inflammatory cytokine IL-8 in HT-29 cells;

[0015] Figure 2 The inhibitory effect of different concentrations of Alnustone on the cellular inflammatory factor IL-8;

[0016] Figure 3 The effects of alder ketone on a mouse model of ulcerative colitis are shown in Figure A, where alder ketone reduces body weight; Figure B reduces the severity of occult blood; and Figure C reduces colonic shortening. Detailed Implementation

[0017] This invention provides the use of alder ketone in the preparation of medicaments for the prevention and / or treatment of ulcerative colitis.

[0018] Alderone is a non-phenolic natural diaryl-heptane compound isolated from alder (Betulaceae family). It is mainly found in the flowers of alder (Betulaceae), the seeds of cardamom (Zingiberaceae family), and the rhizomes of turmeric and turmeric, and possesses a wide range of pharmacological activities. Existing studies have shown that alderone exhibits good pharmacological effects in antiemetic, anti-neuraminidase activity, anti-inflammatory, antibacterial, antitumor, anti-hepatotoxic, and weak estrogenic properties; it is currently widely used in research on malignant tumors. In vivo and in vitro experimental studies of this invention have shown that alderone has a good therapeutic effect on ulcerative colitis.

[0019] In this invention, the preferred dosage of alder ketone is 10-50 mg / kg, more preferably 20-40 mg / kg. By constructing a mouse model of ulcerative colitis, this invention found that alder ketone can alleviate weight loss, occult blood, and colonic shortening caused by ulcerative colitis.

[0020] This invention provides the application of alder ketone in the preparation of reagents for inhibiting the expression of inflammatory factors in human colon adenocarcinoma cell lines. In this invention, the human colon adenocarcinoma cell line is preferably the HT-29 cell line; the inflammatory factor is preferably IL-8. This invention utilizes a TNF-α-induced inflammatory cell model, in which IL-8 expression is significantly increased. Alder ketone treatment can significantly reduce IL-8 expression in the inflammatory cell model, exhibiting an anti-inflammatory effect. In this invention, the concentration of alder ketone used is preferably 5–50 μg / mL, more preferably 10–30 μg / mL.

[0021] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0022] Example 1

[0023] The HT-29 cell line was purchased from the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

[0024] HT-29 cells were used to induce an inflammatory cell model with TNF-α. When the cell monolayer coverage reached 80%–90%, HT-29 cells were treated with 50 ng / μl TNF-α for 2 hours, and the cell pellet and supernatant were collected (1 μl of 50 ng / μl TNF-α was added to 150,000 cells). The secretion of IL-8 protein in the supernatant was detected by ELISA. The results showed that TNF-α significantly promoted the secretion of the inflammatory factor IL-8 from intestinal epithelial cells (such as...). Figure 1 As shown in the figure, the inflammation model was successfully constructed.

[0025] Then, HT-29 cells were pretreated with alnustone at different concentration gradients (0, 5, 10, 15, 30 μg / mL) for 24 h, followed by the addition of TNF-α (50 ng / μL) to induce cellular inflammation. The concentration of IL-8 secreted protein in the cell supernatant was detected by ELISA. The results are as follows. Figure 2 As shown, the alder ketone treatment group significantly reduced the secretion of the inflammatory factor IL-8 in intestinal epithelial cells, suggesting that alder ketone has an anti-inflammatory effect.

[0026] Example 2

[0027] Six mice in each group were allowed free access to 3% DSS daily for seven days to establish the UC model.

[0028] For the constructed UC model mice, UC model mice were treated with intraperitoneal injection of 40 mg / kg alder (dissolved in DMSO). Alder was administered starting on the first day after modeling, i.e., once on days 1, 3, 5, 7, 9, 11, and 13. Clinical indicators such as fecal blood and body weight of the mice were measured daily during this period. Control group mice were injected with the same volume of DMSO daily. At the end of the animal experiment on day 14, all mice were euthanized by cervical dislocation, and the entire colon and rectum of the mice were dissected and removed to measure the length of the colon and rectum.

[0029] The results are as follows Figure 3 As shown, alder ketone can reduce weight loss (A), reduce the severity of occult blood (B), and reduce colonic shortening in mice (C), suggesting that alder ketone has a protective effect against UC.

[0030] As can be seen from the above examples, alder ketone can significantly reduce the secretion of the inflammatory factor IL-8 in intestinal epithelial cells and has an anti-inflammatory effect; alder ketone can reduce weight loss, reduce the severity of occult blood and reduce colonic shortening in mice caused by ulcerative colitis, and has a protective effect against ulcerative colitis; it can be applied to the clinical treatment of ulcerative colitis.

[0031] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The use of alder in the preparation of drugs for the prevention and / or treatment of ulcerative colitis.

2. The application according to claim 1, characterized in that, The dosage of alder ketone is 10~50 mg / kg.

3. The application according to claim 1, characterized in that, The alder ketone can alleviate weight loss, occult blood, and shortened colon caused by ulcerative colitis.

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