CN116942689A - Application of luteolin in preparation of medicines for treating mtx-induced intestinal inflammation - Google Patents
Application of luteolin in preparation of medicines for treating mtx-induced intestinal inflammation Download PDFInfo
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- CN116942689A CN116942689A CN202310941221.8A CN202310941221A CN116942689A CN 116942689 A CN116942689 A CN 116942689A CN 202310941221 A CN202310941221 A CN 202310941221A CN 116942689 A CN116942689 A CN 116942689A
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- IQPNAANSBPBGFQ-UHFFFAOYSA-N luteolin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(O)C(O)=C1 IQPNAANSBPBGFQ-UHFFFAOYSA-N 0.000 title claims abstract description 52
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 title claims abstract description 51
- LRDGATPGVJTWLJ-UHFFFAOYSA-N luteolin Natural products OC1=CC(O)=CC(C=2OC3=CC(O)=CC(O)=C3C(=O)C=2)=C1 LRDGATPGVJTWLJ-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 235000009498 luteolin Nutrition 0.000 title claims abstract description 51
- 230000000968 intestinal effect Effects 0.000 title claims abstract description 34
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 33
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 33
- 239000003814 drug Substances 0.000 title claims abstract description 29
- 229940079593 drug Drugs 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 230000004913 activation Effects 0.000 claims abstract description 5
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
- 108091008099 NLRP3 inflammasome Proteins 0.000 claims abstract description 3
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 claims description 6
- 102100025136 Macrosialin Human genes 0.000 claims description 6
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 5
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 5
- 210000002966 serum Anatomy 0.000 claims description 5
- 108090000426 Caspase-1 Proteins 0.000 claims description 4
- 102100035904 Caspase-1 Human genes 0.000 claims description 4
- 102000003810 Interleukin-18 Human genes 0.000 claims description 4
- 108090000171 Interleukin-18 Proteins 0.000 claims description 4
- 101100404870 Rattus norvegicus Nlrp3 gene Proteins 0.000 claims description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 2
- 238000010276 construction Methods 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 34
- 229960000485 methotrexate Drugs 0.000 description 34
- 241000700159 Rattus Species 0.000 description 22
- 102000000874 Pyrin Domain-Containing 3 Protein NLR Family Human genes 0.000 description 11
- 108010001946 Pyrin Domain-Containing 3 Protein NLR Family Proteins 0.000 description 11
- 230000000694 effects Effects 0.000 description 9
- 210000000813 small intestine Anatomy 0.000 description 9
- 230000002757 inflammatory effect Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 210000002175 goblet cell Anatomy 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 5
- 206010028116 Mucosal inflammation Diseases 0.000 description 4
- 201000010927 Mucositis Diseases 0.000 description 4
- 235000021050 feed intake Nutrition 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
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- 238000002474 experimental method Methods 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- PEFNSGRTCBGNAN-QNDFHXLGSA-N luteolin 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C=C(C=3C=C(O)C(O)=CC=3)OC2=C1 PEFNSGRTCBGNAN-QNDFHXLGSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- IVCZEZUJCMWBBR-UHFFFAOYSA-N 7-O-beta-D-glucopyranosyl-7,3',4'-trihydroxyflavone Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C=C(C=3C=C(O)C(O)=CC=3)OC2=C1 IVCZEZUJCMWBBR-UHFFFAOYSA-N 0.000 description 1
- 241000208828 Caprifoliaceae Species 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 208000015580 Increased body weight Diseases 0.000 description 1
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- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
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- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229930193997 cynaroside Natural products 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- -1 flavonoid compound Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- QZOVLVSTWSTHQN-UHFFFAOYSA-N luteolin 7-O-glucoside Natural products OCC1OC(Oc2cc(O)c3C(=O)C=C(C(=O)c3c2)c4ccc(O)c(O)c4)C(O)C(O)C1O QZOVLVSTWSTHQN-UHFFFAOYSA-N 0.000 description 1
- KBGKQZVCLWKUDQ-UHFFFAOYSA-N luteolin-glucoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC2=C1C(=O)C=C(C=1C=C(O)C(O)=CC=1)O2 KBGKQZVCLWKUDQ-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- PEFNSGRTCBGNAN-UHFFFAOYSA-N nephrocizin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C2C(=O)C=C(C=3C=C(O)C(O)=CC=3)OC2=C1 PEFNSGRTCBGNAN-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of luteolin in preparing a medicine for treating mtx-induced intestinal inflammation, which relates to the technical field of medicine preparation, and the technical scheme is as follows: the luteolin can be used for preparing medicines for treating mtx-induced intestinal inflammation, the effective concentration range of the medicines is 20-40mg/kg, and the medicines relieve mtx-induced intestinal inflammation by inhibiting activation of NLRP3 inflammasome. The invention provides a material basis for treating mtx-induced intestinal inflammation, and can promote the construction of mtx-induced intestinal inflammation treatment drugs and related systems.
Description
Technical Field
The invention relates to the technical field of medicine preparation, in particular to application of luteolin in preparing medicines for treating mtx-induced intestinal inflammation.
Background
The intestinal tract is the largest digestive organ of the body and is also one of the important immune organs. Intestinal mucosa integrity is critical to maintaining normal functioning of the body. When the organism is severely wounded or stressed, pathophysiology such as intestinal mucosa injury and the like can be caused, and a large amount of inflammatory mediators are generated and released by activating the immune response of the organism, so that intestinal inflammation and even systemic inflammatory response are finally initiated. Chemotherapeutic agents, while toxic to cancer cells, can also cause serious adverse effects. Among them, intestinal mucositis (Intestinal mucositis, IM) is one of the major gastrointestinal side effects. The incidence of IM caused by chemotherapy is about 40%, and especially when using chemotherapeutics such as Methotrexate (MTX), 5-fluorouracil (5-Fu), cytarabine, etc., the incidence of intestinal mucositis can be as high as 90%. There is no effective treatment of MTX-induced intestinal mucositis to date.
Studies have shown that NLRP3 inflammatory bodies play an important role in inflammatory diseases of the gut, e.g., NLRP3 is highly expressed in gut inflammation and damaged tissues. Activation of the NLRP3 inflammatory corpuscles induces its cleavage and release of IL-1 beta and IL-18, thereby inducing further development of inflammation.
Luteolin (Cynaroside), also known as luteolin-7-O-glucoside, is a flavonoid compound widely existing in medicinal plants of Caprifoliaceae, has various biological activities such as anti-inflammatory, antiviral and antitumor, and has protective effects on cardiovascular and nervous systems. However, the role of luteolin in mtx-induced intestinal inflammation is not yet clear.
Disclosure of Invention
The invention aims to provide application of luteolin in preparing medicines for treating mtx-induced intestinal inflammation, provides a material basis for treating mtx-induced intestinal inflammation, and can promote construction of mtx-induced intestinal inflammation treatment medicines and related systems.
The technical aim of the invention is realized by the following technical scheme: the invention provides application of luteolin in preparing a medicament for treating mtx-induced intestinal inflammation, wherein the luteolin can be used for preparing a medicament for treating mtx-induced intestinal inflammation, and the medicament reduces mtx-induced intestinal inflammation by inhibiting activation of NLRP3 inflammasome.
The invention is further provided with: the drug can down-regulate mtx to induce the expression level of rat NLRP3, clear caspase 1 and clear IL-1 beta.
The invention is further provided with: the medicine can reduce mtx induced levels of TNF-alpha, IL-1 beta and IL-18 in rat serum, and inhibit CD68 positive cell rate.
The invention is further provided with: the effective concentration range of the medicine is 20-40mg/kg.
In summary, the invention has the following beneficial effects: compared with the prior art, the luteolin can relieve mtx-induced intestinal inflammation by inhibiting the activation of NLRP3 inflammatory bodies, and further, the luteolin is applied to the preparation of medicines for treating mtx-induced intestinal inflammation, so that a material basis is provided for treating mtx-induced intestinal inflammation, and construction of medicines and related systems for treating mtx-induced intestinal inflammation can be promoted.
Drawings
FIG. 1 is a graph showing the effect of luteolin of the present invention on MTX-induced growth performance in rats. (data expressed as mean ± SD, n=6, #p <0.01, compared to control group, # compared to MTX group, P < 0.01);
FIG. 2 is the effect of luteolin of the present invention on MTX-induced disease index in rats. (data expressed as mean ± SD, n=6, #p <0.01, compared to control group, # compared to MTX group, P < 0.01);
FIG. 3 is a graph showing the effect of luteolin of the present invention on MTX-induced serum proinflammatory factor levels in rats. (data expressed as mean ± SD, n=6, #p <0.01, compared to control group, # compared to MTX group, P < 0.01);
FIG. 4 is a graph showing the effect of luteolin of the present invention on MTX-induced pathological changes in the intestinal tract of rats. (A) Small intestine histopathology H & E staining, (B) statistical analysis of inflammation scores. (data are expressed as mean ± SD, n=6, #p <0.01, compared to control group, P <0.01, scale bar represents 100 μm);
FIG. 5 is the effect of luteolin of the present invention on MTX-induced goblet cells in rats. (A) PAS staining detects goblet cells, (B) statistical analysis of goblet cell numbers. (data are expressed as mean ± SD, n=6, #p <0.01, compared to control group, P <0.01, scale bar represents 100 μm);
FIG. 6 is the effect of luteolin of the present invention on MTX-induced rat NLRP3 inflammatory small associated proteins. (data are expressed as mean ± SD, n=3, #p <0.01, compared to control group, P <0.01, scale bar represents 100 μm);
FIG. 7 shows the detection of CD68 cell positive rate by immunofluorescence method of the present invention. (data are expressed as mean ± SD, n=3, #p <0.01, compared to control group, P <0.01, scale bar represents 100 μm);
FIG. 8 shows the detection of NLRP3 protein expression level by immunofluorescence method of the present invention. (data are expressed as mean ± SD, n=3, #p <0.01, compared to control, P <0.01, scale bar represents 100 μm compared to MTX group
Detailed Description
For the purpose of making apparent the objects, technical solutions and advantages of the present invention, the present invention will be further described in detail with reference to the following examples and the accompanying drawings, wherein the exemplary embodiments of the present invention and the descriptions thereof are for illustrating the present invention only and are not to be construed as limiting the present invention.
Examples:
in the embodiment, animal simulation experiments are carried out by adopting male SD rats, so that the effect of luteolin on mtx-induced intestinal inflammation is more intuitively displayed. The method comprises the following specific steps:
30 healthy 6-8 week old male SD rats 211.38 + -3.25 g were selected and randomly divided into five groups of 6 rats each. The control group, the model group (MTX group), the low dose group of luteolin (MTX+10 mg/kg of luteolin), the medium dose group of luteolin (MTX+20 mg/kg of luteolin) and the high dose group of luteolin (MTX+40 mg/kg of luteolin) are respectively given.
The duration of the experiment was 7 days.
The model group was established by intraperitoneal injection of 7mg/kg/d MTX for the first 3 days, followed by feeding with an equal amount of physiological saline for the last 4 days.
7mg/kg/d MTX was intraperitoneally injected 3 days before the low dose group of luteolin, and 10mg/kg of luteolin was fed to each rat in the low dose group of luteolin four days later.
7mg/kg/d MTX was intraperitoneally injected 3 days before the medium dose group of luteolin, and rats in each medium dose group of luteolin were fed with 20mg/kg of luteolin four days later.
7mg/kg/d MTX was intraperitoneally injected 3 days before the high dose group of luteolin, and each rat in the high dose group of luteolin was fed with 40mg/kg luteolin, and four days later, each rat in the high dose group of luteolin was fed with 40mg/kg luteolin.
The control group was fed an equal amount of physiological saline every day.
Feed intake and final body weight of each group of rats were recorded from the beginning of the experiment. The feed intake and weight are shown in figure 1. The final body weight of the rats in the MTX group was significantly reduced compared to the control group. Rats with 20 or 40mg/kg luteolin added had significantly increased body weight (p < 0.01). Meanwhile, the daily feed intake of rats in the MTX group is gradually reduced, and 40mg/kg of luteolin can increase the daily feed intake of rats induced by MTX.
24 hours after the 7 th day of feeding, rats were anesthetized with intraperitoneal injection of 2% sodium pentobarbital and disease activity index was calculated, and the results are shown in fig. 2. Compared with MTX, the addition of 20 and 40mg/kg luteolin can significantly reduce the disease index of rats.
Blood and small intestine tissue were collected and levels of TNF- α, IL-1β and IL-18 were measured in the blood using the Elisa method. The detection results are shown in FIG. 3. Inflammation generally occurs with the production and secretion of proinflammatory cytokines in the circulation. Thus, we examined the levels of representative inflammatory factors TNF- α, IL-1β and IL-18IL in serum. The levels of these cytokines were significantly up-regulated (p < 0.01) in the MTX group compared to the control group, whereas those in serum of the luteolin group (20 or 40 mg/kg) were significantly lower than those in the MTX group (p < 0.01), indicating positive anti-inflammatory effects of luteolin.
The HE method is used for detecting pathological changes of small intestine, and the detection result is shown in figure 4. H & E staining examined small intestine histological changes (fig. 4A). Compared with the control group, the intestinal tissues of the rats dosed with 40mg/kg luteolin are complete, and no inflammatory reaction occurs. However, HE staining showed that MTX group showed typical pathological changes (inflammatory cell infiltration, mucosal layer destruction, gland dilation, intestinal villus structure disorder). Luteolin significantly ameliorates these MTX-induced morphological changes. In addition, luteolin also reduces the intestinal inflammation score (fig. 4B).
PAS method detects the change in the number of goblet cells in the small intestine. The results are shown in FIG. 5, and the results of the staining of the small intestine PAS are shown in FIG. 5A. MTX resulted in a significant decrease in small intestine goblet cell numbers compared to the control group (p <0.01, fig. 5B), whereas MTX induced increases in rat goblet cell numbers when 20 or 40mg/kg luteolin was added (p <0.01, fig. 5B).
The protein expression level of NLRP3, clear caspase-1 (p 20), clear IL-1β (p 17) in small intestine tissues was detected by Western blot, and the results are shown in FIG. 6. The western blotting results show that the expression level of NLRP3, clear caspase 1 and clear IL-1β in the MTX group is significantly higher than that in the control group (p < 0.01), suggesting that NLRP3 inflammatory corpuscles are activated. The expression level of the protein can be obviously reduced by treating with 20 or 40mg/kg luteolin.
The detection results of the CD68 cell positive rate and NLRP3 protein expression level in the small intestine by immunofluorescence are shown in fig. 7 and 8. Immunofluorescence results showed that MTX group CD68 cell positive rate and NLRP3 protein expression level were significantly increased compared to control group. When treated with 20 or 40mg/kg luteolin, CD68 cell positive rate and NLRP3 protein expression level were significantly lower than in MTX group.
The present embodiment is only for explanation of the present invention and is not to be construed as limiting the present invention, and modifications to the present embodiment, which may not creatively contribute to the present invention as required by those skilled in the art after reading the present specification, are all protected by patent laws within the scope of claims of the present invention.
Claims (4)
1. The application of luteolin in preparing a medicament for treating mtx-induced intestinal inflammation is characterized in that: the luteolin can be used for preparing medicines for treating mtx-induced intestinal inflammation, and the medicines relieve mtx-induced intestinal inflammation by inhibiting activation of NLRP3 inflammasome.
2. Use of luteolin according to claim 1 for the preparation of a medicament for the treatment of mtx-induced intestinal inflammation, characterized in that: the drug can down-regulate mtx to induce the expression level of rat NLRP3, clear caspase 1 and clear IL-1 beta.
3. Use of luteolin according to claim 1 for the preparation of a medicament for the treatment of mtx-induced intestinal inflammation, characterized in that: the medicine can reduce mtx induced levels of TNF-alpha, IL-1 beta and IL-18 in rat serum, and inhibit CD68 positive cell rate.
4. Use of luteolin according to claim 1 for the preparation of a medicament for the treatment of mtx-induced intestinal inflammation, characterized in that: the effective concentration range of the medicine is 20-40mg/kg.
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