Application of chamomile in preparation of medicine for treating intestinal diseases
By using genusin as an NLRP3 inflammasome inhibitor, the activity of the NLRP3 signaling pathway is inhibited, and the problem of lack of effective treatment of inflammatory bowel disease in the prior art is solved, and effective treatment of inflammatory bowel disease is achieved.
Patent Information
- Application Number
- CN202411834895.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-13
- Publication Date
- 2025-03-11
Smart Images
Figure CN119587531A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of medical technology, and in particular relates to the application of chamomile in the preparation of medicines for treating intestinal diseases. Background Art
[0002] NLRP3 inflammasome is an important component of innate immunity, and its activation helps to resist pathogen infection and stress injury, but uncontrolled activation can lead to amplified inflammatory effects and organ damage. Abnormal activation of NLRP3 inflammasome is closely related to the occurrence and development of systemic multi-organ diseases such as acute inflammation, gouty arthritis, and ulcerative colitis. Therefore, targeting the abnormal activation of NLRP3 inflammasome can be used to treat these inflammatory diseases. At present, there have been many basic studies on the use of NLRP3 inflammasomes to treat inflammatory diseases, but there are no drugs targeting NLRP3 inflammasomes for the treatment of inflammatory diseases in the clinic.
[0003] Coleus is a sesquiterpene lactone isolated from crinoids and is a selective retinoid X receptor α agonist. It regulates the mTOR signaling pathway by inhibiting the generation of ROS. It induces apoptosis and autophagy and has anti-tumor activity. Coleus (0-20μM, 24-72h) significantly inhibits the cell viability of hepatoma cells and induces apoptosis and autophagy. Coleus (BigV, 5, 10, 20mg / kg) exerts anti-tumor activity in the HepG2 xenograft tumor model.
[0004] At present, jinjulin is mainly used in cancer-related research, and its role in targeting abnormal activation of NLRP3 inflammasomes has not been reported. Therefore, clarifying the efficacy of jinjulin in diseases related to abnormal activation of NLRP3 inflammasomes and proving the drug's effect on inflammatory bowel disease in preclinical studies is expected to achieve a "new" use of "old" drugs in the treatment of inflammatory bowel disease! Summary of the invention
[0005] The embodiments of the present invention provide the use of chrysanthemum in the preparation of drugs for treating intestinal diseases, aiming to solve the problem of lack of effective and specific drugs for the treatment of inflammatory bowel disease. The present invention confirms that chrysanthemum has the effect of NLRP3 inflammasome inhibitor, and is used for the treatment of inflammatory bowel disease by inhibiting the activity of NLRP3 signaling pathway.
[0006] The technical solution of the present invention is achieved in this way:
[0007] The application of jinchatin in the preparation of drugs for treating intestinal diseases is mainly based on the fact that jinchatin can be used for the treatment of inflammatory bowel disease by inhibiting the activity of NLRP3 signaling pathway.
[0008] Furthermore, the intestinal disease is preferably inflammatory bowel disease.
[0009] Furthermore, the jewelweed is an inhibitor of NLRP3 inflammasome, which is used to treat inflammatory bowel disease by inhibiting abnormal activation of NLRP3 inflammasome. The NLRP3 inflammasome inhibitor is an inhibitor of abnormal activation of NLRP3 inflammasome.
[0010] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:
[0011] The present invention verifies through experiments that jinjulin can be used to treat inflammatory bowel disease by inhibiting the activity of the NLRP3 signaling pathway. Jinjulin can be applied to the treatment of inflammatory bowel disease, opening up a new use of jinjulin in the preparation of drugs for treating intestinal diseases. The present invention provides a new therapeutic strategy for the drug treatment of inflammatory bowel disease and opens up a new direction. In addition, jinjulin, as an inhibitor of abnormal activation of NLRP3 inflammasomes, not only further enriches the research on the treatment of inflammatory-related diseases with inhibitors of abnormal activation of NLRP3 inflammasomes, but also provides a new direction for the clinical transformation of drugs of inhibitors of abnormal activation of NLRP3 inflammasomes. BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Figure 1 This is a graph showing the detection results of the IL-1β level released by mouse peritoneal macrophages after adding 297 compounds in Example 1 of the present invention.
[0013] Figure 2 This is a graph showing the detection results of the IL-1β level released by mouse peritoneal macrophages after the addition of chamomile extract in Example 2 of the present invention.
[0014] Figure 3 This is a graph showing the detection results of the TNF-α level released by mouse peritoneal macrophages after the addition of chamomile extract in Example 2 of the present invention.
[0015] Figure 4 This is a diagram of the detection results of WB (Western Blot) in Example 3 of the present invention. DETAILED DESCRIPTION
[0016] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0017] In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the fact that ordinary technicians in the field can implement it. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.
[0018] At present, there is a lack of effective and specific drugs for the treatment of inflammatory bowel disease. In order to solve the above technical problems, the present invention proposes the use of caesalpin in the preparation of drugs for treating intestinal diseases.
[0019] Example 1
[0020] In order to find out compounds that can inhibit the abnormal activation of NLRP3 inflammasomes. A compound library containing 297 compounds was used. This compound library contains a large number of small molecule compounds, each of which is an inhibitor of inflammation. During the experiment, 6-8 week old C57BL / 6 mice were first selected, and 3% thioglycolate broth was injected intraperitoneally to induce the production of mouse peritoneal macrophages. After extracting mouse peritoneal macrophages, they were plated in 24-well plates with 500,000 cells per well. After the cells adhered to the wall, LPS+Nig was used to induce abnormal activation of NLRP3 inflammasomes. Compounds were then used for intervention. In this way, it can be ensured that each compound treated the cells separately. The changes in abnormal activation of cell NLRP3 inflammasomes were observed by ELISA experiments. After a lot of screening and testing, it was finally found that jinjucin showed the best inhibitory effect. The specific steps are as follows:
[0021] 1. Purchased from the library of anti-inflammatory compound inhibitors of Shanghai Taoshu Company.
[0022] 2. Select 6-8 week old C57BL / 6 mice and induce the production of peritoneal macrophages by intraperitoneal injection of 3% thioglycolate broth.
[0023] 3. After extracting mouse peritoneal macrophages, they were plated in a 24-well plate with 500,000 cells per well. After the cells adhered to the wall, LPS+NiG was used to induce abnormal activation of NLRP3 inflammasomes.
[0024] 4. After inducing abnormal activation of NLRP3 inflammasome, different compounds were added to each well, and the concentration of the compounds was 10 μM / well.
[0025] 5. After 1 hour, the cell supernatant of each well was collected and the ELISA kit was used to detect the release level of IL-1β after treatment with different compounds.
[0026] The results are as follows Figure 1It showed that after adding 297 compounds, the level of IL-1β released by peritoneal macrophages of mice added with chamomile was the lowest compared with the induced group.
[0027] Example 2
[0028] To explore whether galanthus can affect changes in other inflammatory indicators. The specific steps are as follows:
[0029] 1. Select 6-8 week old C57BL / 6 mice and induce the production of peritoneal macrophages by intraperitoneal injection of 3% thioglycolate broth.
[0030] 2. After extracting mouse peritoneal macrophages, they were plated in a 24-well plate with 500,000 cells per well. After the cells adhered to the wall, LPS+NiG was used to induce abnormal activation of NLRP3 inflammasomes.
[0031] 3. After inducing abnormal activation of NLRP3 inflammasome, different concentrations of chamaedrylamine were added to each well, with concentrations of 0.25, 0.5, and 1 μM / well, respectively.
[0032] 4. After 1 hour, the cell supernatant of each well was collected and the release levels of IL-1β and TNF-α after treatment with different concentrations of caesalpin were detected using ELISA kit.
[0033] The results are as follows Figure 2 , Figure 3 The results showed that chamaedryl only reduced the release of IL-1β from mouse peritoneal macrophages, but had no effect on the release of TNF-α.
[0034] Example 3
[0035] To prove that jinjulin inhibits the phenotype of abnormal activation of NLRP3 inflammasome in mouse peritoneal macrophages. Through WB experiments, it was determined that jinjulin can clearly inhibit the abnormal activation of NLRP3 inflammasome in mouse peritoneal macrophages. The specific steps are as follows:
[0036] 1. Select 6-8 week old C57BL / 6 mice and induce the production of peritoneal macrophages by intraperitoneal injection of 3% thioglycolate broth.
[0037] 2. After extracting mouse peritoneal macrophages, they were plated in 6-well plates with 2 million cells per well. After the cells adhered to the wall, LPS+NiG was used to induce abnormal activation of NLRP3 inflammasomes.
[0038] 3. After inducing abnormal activation of NLRP3 inflammasome, different concentrations of chamaedryl were added to each well, with concentrations of 0.25, 0.5, and 10 μM / well, respectively.
[0039] 4. After 1 hour, the cell supernatant and cell pellet of each well were collected. WB experiment was used to detect the release levels of IL-1βP17 and Caspase-1P10 in the cell supernatant after treatment with different concentrations of caerulein, and the expression levels of pro-IL-1β, pro-Caspase-1, and GSDMD in the cell pellet after treatment with different concentrations of caerulein were detected.
[0040] WB (Western Blot) results are as follows Figure 4 It was shown that galactin inhibited the activation of Caspase-1 and IL-1β in the supernatant and weakened the cleavage of GSDMD in cells, but did not impair the precursors of IL-1β and Caspase-1.
[0041] Example 4
[0042] Animal in vivo experiments have verified that jasmine can be used as a drug for the treatment of inflammatory bowel disease. The specific steps are as follows:
[0043] 1. Select 6-8 week old C57BL / 6 mice. Add 3% DSS to the mice's daily drinking water for 10 days. From day 0 to day 9, inject DMSO (control group) or chamomile extract intraperitoneally once a day.
[0044] 2. Record the clinical evaluation of each group every day, including body weight, stool characteristics and fecal occult blood test.
[0045] 3. After 10 days, the animals were killed by cervical dislocation, and the colon was removed and the colon part was measured and recorded.
[0046] 4. After the anus is removed, the posterior 0.5 cm is retained and placed in paraformaldehyde fixative for HE examination.
[0047] The results showed that jinchain can alleviate the increase of pathological indicators related to inflammatory bowel disease in mice and significantly reduce the pathological changes in the inflammatory bowel disease mouse model. It can be used to treat inflammatory bowel disease.
[0048] In summary, the embodiments of the present invention confirm that chrysanthemumin has the effect of NLRP3 inflammasome inhibitor, and chrysanthemumin can be used for the treatment of inflammatory bowel disease by inhibiting the activity of NLRP3 signaling pathway, thereby confirming the application of chrysanthemumin in the preparation of drugs for treating intestinal diseases.
[0049] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.
Claims
1. Application of chrysanthemum in the preparation of drugs for the treatment of intestinal diseases.
2. The use of jinchain in the preparation of a drug for treating intestinal diseases according to claim 1, characterized in that: The intestinal disease is inflammatory bowel disease.
3. The use of jinchain in the preparation of a drug for treating intestinal diseases according to claim 1, characterized in that: The jewelweed extract is an inhibitor of NLRP3 inflammasome.