CN116920012A - Application of clinopodium polycephalum in preparing medicament for treating ulcerative colitis - Google Patents
Application of clinopodium polycephalum in preparing medicament for treating ulcerative colitis Download PDFInfo
- Publication number
- CN116920012A CN116920012A CN202210349118.XA CN202210349118A CN116920012A CN 116920012 A CN116920012 A CN 116920012A CN 202210349118 A CN202210349118 A CN 202210349118A CN 116920012 A CN116920012 A CN 116920012A
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- China
- Prior art keywords
- ulcerative colitis
- clinopodium polycephalum
- extract
- clinopodium
- preparation
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
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Abstract
The application relates to the technical field of medicines, in particular to an application of clinopodium polycephalum in preparing a medicine for treating ulcerative colitis. Use of herba Clinopodii in preparing medicine for treating ulcerative colitis is provided. When the clinopodium polycephalum is used for treating ulcerative colitis, the application can effectively reduce DAI score, inhibit inflammatory factor level in blood plasma, lighten inflammatory response of colonic mucosa tissue, play a role in protecting colonic mucosa, further achieve the treatment effect and have wide application prospect.
Description
Technical Field
The application relates to the technical field of medicines, in particular to an application of clinopodium polycephalum in preparing a medicine for treating ulcerative colitis.
Background
Ulcerative colitis (ulcerative colitis, UC) is a chronic, non-specific inflammatory disease of the intestinal tract, lesions mainly involving the parts of the rectum, colonic mucosa and submucosa. Clinically, diarrhea, mucopurulent stool, abdominal pain, and complications such as megacolon, lower gastrointestinal hemorrhage, and intestinal perforation may be involved. The traditional Chinese medicine composition has the characteristics of complex pathogenesis, high intractability, repeatability, continuity, recurrence rate, high cure difficulty and the like. In recent years, the prevalence of UC in China has reached one ten thousandth, and the trend of increasing year by year is seen.
In clinical practice, conventional treatment of UC relies on drugs such as aminosalicylic acid, corticosteroids, immunomodulators, etc. The long-term western medicine treatment not only brings great economic burden to patients, but also can repeatedly attack after treatment and simultaneously has serious side effects.
Herba Clinopodii, also known as herba Agastaches, clinopodium polycephalum herba Clinopodii, herba Sparassis, is a dry aerial part of Labiatae plant Lanterna Clinopodium polycephalum (Vaniot) C.Y.wu et Hsuan ex P.S.Hsu or Clinopodium polycephalum Clinopodium chinense (benth.) O.ktze. It is received in China pharmacopoeia of 2015 edition, slightly bitter and astringent in taste and cool in nature. The broken blood flow has a long medical history in China, has the effects of cooling blood and stopping bleeding, and is mainly used for treating bleeding diseases such as metrorrhagia, hematuria, epistaxis, gingival bleeding, traumatic hemorrhage, hysteromyoma hemorrhage and the like.
The related patent reports the effect of the total flavonoids extract of clinopodium polycephalum in treating and preventing hemorrhagic diseases (Chinese patent: clinopodium polycephalum total flavonoids extract, preparation method and application, publication No. CN 1891255A). The patent only investigated the effect of total flavonoids extract of clinopodium polycephalum in treating and preventing hemorrhagic diseases. According to the ninth edition of the science of the people health publishing company: hemorrhagic diseases are a group of diseases characterized by spontaneous or mild post-injury excessive bleeding due to defects or abnormalities in hemostatic mechanisms such as blood vessels, platelets, coagulation, anticoagulation, fibrinolysis, etc. caused by congenital or genetic factors. The pathogenesis of hemorrhagic diseases can be divided into abnormalities of the vessel wall, of platelets and of the coagulation fibrinolytic system. And does not include bleeding due to surgery, trauma or ulcers.
The Ulcerative Colitis (UC) is a chronic nonspecific inflammatory disease of intestinal tracts, and the main cause is the damage of the intestinal mucosa barrier, which does not belong to the category of hemorrhagic diseases. According to the ninth edition of the science of the people health publishing company: the pathogenesis of UC is related to abnormal immune unbalance of intestinal tract caused by the interaction of environment, genetics, intestinal microecology and other factors, various factors cause the activation of inflammatory pathways of the organism, the secretion of inflammatory factors (such as IL-6, TNF-alpha, IL-4 and the like) is increased, the unbalance of inflammatory factors/anti-inflammatory factors causes continuous inflammation of intestinal mucosa and the damage of barrier function.
Modern scientific researches have shown that clinopodium polycephalum has anti-inflammatory, analgesic and antibacterial activities. No report on the application of the clinopodium polycephalum extract in preparing the medicines for treating ulcerative colitis is found in the prior art.
Disclosure of Invention
The application aims to provide an application of clinopodium polycephalum extract in preparing a medicament for treating ulcerative colitis.
In order to achieve the above purpose, the application adopts the technical scheme that:
an application of herba Clinopodii in preparing medicine for treating ulcerative colitis is provided.
The herba Clinopodii is dry aerial part or dry whole plant of Clinopodium polycephalum herba Clinopodii (Clinopodium chinense) or herba Physalis Pubescentis (Clinopodium polycephalum) of Labiatae.
The herba Clinopodii is herba Clinopodii extract.
The herba Clinopodii extract is obtained by extracting dried aerial parts of herba Clinopodii and/or herba Physalis Pubescentis or dried whole plant with water or organic solvent.
The herba Clinopodii extract contains one or more of total extract, total flavone, total diterpene and total triterpene extracted from herba Clinopodii and/or herba Physalis chinensis.
The application of the monomer compound Sarurolide obtained by extracting from clinopodium polycephalum in preparing the medicine for treating ulcerative colitis.
The method for extracting the clinopodium polycephalum extract comprises the following steps: collecting 50KG of herba Clinopodii, drying, cutting, and reflux extracting with 10-15 times of solvent. Recovering solvent under reduced pressure to obtain extract, extracting with petroleum ether, ethyl acetate and n-butanol, and concentrating the ethyl acetate layer extract on polyamide column to obtain herba Clinopodii total flavonoids extract. Subjecting n-butanol layer extract to D101 macroporous adsorbent resin chromatography, and eluting with 80% ethanol solution to obtain total triterpene extract. Concentrating petroleum ether layer into extract, subjecting to AB8 macroporous adsorbent resin chromatography to obtain total diterpenoid extract, and subjecting the monomer compound Saturolide to ODS column treatment and HPLC treatment.
(3bR,5aR,7S,9aR,9bS)-5a-hydroxy-7,9b-dimethyl-7-vinyl-3b,4,5,5a,6,7,8,9
,9a,9b,10,11-dodecahydrophenanthro[1,2-c]furan-1(3H)-one(Saturolide)
Further, the extract, the effective parts and the monomers of the clinopodium polycephalum are taken as active ingredients, and the active ingredients and pharmaceutically acceptable carriers, auxiliary materials or pharmaceutically acceptable excipients form a pharmaceutical preparation.
The dosage forms of the pharmaceutical preparation are liquid dosage forms, solid dosage forms, semisolid dosage forms, gas dosage forms, enema use and the like.
Wherein the liquid dosage forms are mixture, oral liquid, medicated wine, tincture, syrup, injection, etc.; the solid dosage forms are powder, granule, tablet, capsule, dripping pill, membrane, suppository and micropill; semisolid dosage forms such as ointment, paste, extract, lick, etc.; the gas dosage form is aerosol, inhalant, etc.
The ulcerative colitis refers to a chronic nonspecific inflammatory bowel disease which takes mucopurulent bloody stool, abdominal pain and diarrhea as main clinical manifestations, and the pathology is represented by large-area superficial ulcers of rectum, colon mucous membrane and submucosa, and can also involve concurrent diseases such as toxic megacolon, lower digestive tract hemorrhage, intestinal perforation and the like.
The Clinopodium polycephalum herba Clinopodii extract has effects of inhibiting weight loss, blood and stool condition of UC mice, and reducing DAI score.
Further, the clinopodium polycephalum extract has the effects of improving inflammatory response caused by ulcerative colitis, improving tissue structural damage and protecting colonic mucosa barrier.
Furthermore, the clinopodium polycephalum extract has the effects of increasing the content of colon oxidation factor MDA in colon tissues and reducing the content of colon oxidation factors SOD, GSH and inflammatory factors PGE 2.
Furthermore, the clinopodium polycephalum extracts have the effects of reducing the proinflammatory cytokines IL-6, TNF-alpha and the immunoregulatory factor INF-gamma in blood plasma and improving the level of the anti-inflammatory cytokines IL-4.
Furthermore, the clinopodium polycephalum extract can regulate and balance the immune system of the organism by regulating the content of INF-gamma and IL-4, thereby achieving the effect of reducing inflammatory reaction.
Furthermore, the clinopodium polycephalum extract can reduce inflammatory reaction of colonic mucosa tissues by inhibiting NF- κB level, and can play a role in protecting colonic mucosa. Thereby having the application of preparing the medicine for treating ulcerative colitis.
The application has the advantages that
When the clinopodium polycephalum extract is used for treating ulcerative colitis, the application can effectively reduce DAI score, improve colon oxidation factor MDA content in colon tissue, reduce colon oxidation factor SOD, GSH and inflammatory factor PGE2 content, reduce pro-inflammatory cytokines IL-6 and TNF-alpha in blood plasma, improve anti-inflammatory cytokine IL-4, regulate autoimmunity by inhibiting inflammatory factors in blood plasma, further improve inflammatory response caused by ulcerative colitis, improve tissue structure injury and protect colon mucosa barrier, and simultaneously reduce inflammatory response of colon mucosa tissue by inhibiting NF-kappa B, play a role in protecting colon mucosa, thereby achieving the treatment effect of the colon mucosa and having wide application prospect.
Drawings
FIG. 1 is a hydrogen spectrum of a monomer compound Saturolide in example 1 of the present application;
FIG. 2 is a carbon spectrum of the monomer compound Saturolide in example 1 of the present application;
FIG. 3 is a schematic diagram showing the effect of the extract of Clinopodium polycephalum on the weight of UC mice obtained by extracting different raw materials in example 3 of the present application;
FIG. 4 is a graph showing the effect of different raw material extractions to obtain Clinopodium polycephalum extract on DAI score of UC mice in example 3 of the present application;
FIG. 5 is a graph showing the effect of the extract of Clinopodium polycephalum on the colon length of UC mice obtained by extracting different materials in example 3 of the present application;
FIG. 6 is a graph showing colon HE staining of UC mice with extract of Clinopodium polycephalum obtained by extracting different materials in example 3 of the present application;
FIG. 7 is a schematic diagram showing the effect of the extract of Clinopodium polycephalum on MDA and SOD content in colon tissue of UC mice according to the application;
FIG. 8 is a graph showing the effect of different raw material extractions in example 3 of the present application on the levels of IL-6, TNF- α, INF- γ and IL-4 in the plasma of UC mice;
Detailed Description
The use of clinopodium polycephalum extract for treating ulcerative colitis is described in detail below by way of specific examples.
The clinopodium polycephalum extract is extracted according to the Chinese herbal medicine extraction mode recorded in Chinese medicine extraction and separation technology; for example, an extract obtained by extracting a raw material (clinopodium polycephalum) with a solvent such as water, alcohol, etc., and the obtained extract does not change its extraction components depending on the extraction solvent; further, the blood flow interrupting extracts of the following examples can be obtained as follows: collecting dry whole herb (such as herba Clinopodii or herba Physalis), cutting, soaking in 10-15 times of solvent (such as water and organic solvent), and reflux extracting to obtain herba Clinopodii extract and monomer compound Saturolide.
Example 1
The method for extracting the clinopodium polycephalum extract comprises the following steps:
drying whole herb of 50KG Clinopodium polycephalum herba Clinopodii, cutting, soaking in 750L70% ethanol, heating and reflux extracting at 70deg.C for three times until the extractive solution is clear, and taking as the whole extract;
recovering solvent under reduced pressure to obtain extract, sequentially extracting with petroleum ether, ethyl acetate and n-butanol, concentrating ethyl acetate layer extract on polyamide column, eluting with 40%, 60% and 80% ethanol as eluent, and collecting 60% eluent to obtain herba Clinopodii total flavonoids extract.
Subjecting the n-butanol layer extract to D101 macroporous adsorbent resin chromatography, eluting with 40%, 60% and 80% ethanol, and collecting 80% ethanol eluate to obtain total triterpene extract.
Concentrating the petroleum ether layer into extract, subjecting to AB8 type macroporous adsorbent resin chromatography, eluting with 70%, 80% and 90% ethanol eluents, and collecting 80% eluate to obtain total diterpenoid extract.
The monomer compound Saturolide is loaded on ODS column from the total diterpene extract, eluting with 40%, 60% and 80% ethanol-water eluent, collecting 80% eluent, and eluting with methanol: HPLC treatment of the water (80:100) system afforded the monomer compound at about 27 min. (see FIGS. 1 and 2)
(3bR,5aR,7S,9aR,9bS)-5a-hydroxy-7,9b-dimethyl-7-vinyl-3b,4,5,5a,6,7,8,9,9a,9b,10,11-dodecahydrophenanthro[1,2-c]furan-1(3H)-one(Saturolide)
Meanwhile, replacing the raw materials with the cape jasmine to obtain the clinopodium polycephalum extract according to the operation, and further purifying to obtain the total flavonoids, the total triterpenes and the total diterpenoids.
Example 2 formulation
The extract, the effective parts and the monomers of the clinopodium polycephalum are active ingredients, and the active ingredients and pharmaceutically acceptable carriers, auxiliary materials or pharmaceutically acceptable excipients form a pharmaceutical preparation.
The dosage forms of the pharmaceutical preparation are liquid dosage forms, solid dosage forms and the like
Wherein the liquid dosage form is oral liquid or injection; the solid dosage forms include granule, tablet and capsule.
2.1 preparation of oral liquid
Extracted from Clinopodium polycephalum:
dissolving herba Clinopodii extract fine powder 1g in distilled water, regulating pH with dilute sodium bicarbonate solution, adding antiseptic 0.05% potassium sorbate, packaging, and sterilizing.
Dissolving 1g of total flavonoid extract fine powder in distilled water, regulating pH with dilute sodium bicarbonate solution, adding 0.05% potassium sorbate as antiseptic, packaging, and sterilizing.
Dissolving 1g of total diterpenoid extract fine powder in distilled water, regulating the pH value with dilute sodium bicarbonate solution, adding 0.05% potassium sorbate as preservative, packaging, and sterilizing.
Dissolving 1g of total triterpene extract fine powder in distilled water, regulating pH with dilute sodium bicarbonate solution, adding 0.05% potassium sorbate as antiseptic, packaging, and sterilizing.
Taking 1g of a monomer compound Saturolide, dissolving the monomer compound Saturolide in distilled water, regulating the pH value by using a dilute sodium bicarbonate solution, adding 0.05% of preservative potassium sorbate, filling and sterilizing.
Extracted from the plant of the genus Lantern:
dissolving herba Clinopodii extract fine powder 1g in distilled water, regulating pH with dilute sodium bicarbonate solution, adding antiseptic 0.05% potassium sorbate, packaging, and sterilizing.
Dissolving 1g of total flavonoid extract fine powder in distilled water, regulating pH with dilute sodium bicarbonate solution, adding 0.05% potassium sorbate as antiseptic, packaging, and sterilizing.
Dissolving 1g of total diterpenoid extract fine powder in distilled water, regulating the pH value with dilute sodium bicarbonate solution, adding 0.05% potassium sorbate as preservative, packaging, and sterilizing.
Dissolving 1g of total triterpene extract fine powder in distilled water, regulating pH with dilute sodium bicarbonate solution, adding 0.05% potassium sorbate as antiseptic, packaging, and sterilizing.
2.2 preparation of tablets
Extracted from Clinopodium polycephalum:
taking 1g of clinopodium polycephalum extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of total flavonoid extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of total diterpenoid extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of total triterpene extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of a monomer compound Saturolide, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Extracted from the plant of the genus Lantern:
taking 1g of clinopodium polycephalum extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of total flavonoid extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of total diterpenoid extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Taking 1g of total triterpene extract, preparing into fine powder, adding a proper amount of starch slurry as an adhesive and a proper amount of starch as a diluent, and tabletting.
Example 3 test for efficacy verification of Clinopodium polycephalum
3.1 laboratory animals and materials
Experimental animals: BALB/c mice aged 6-8 weeks.
Experimental materials: dextran Sodium Sulfate (DSS), mesalazine (5-ASA), the clindamycin extract obtained by the extraction of example 1, various active sites and monomers, paraformaldehyde, ethanol, hematoxylin eosin staining kit, urine fecal occult blood detection kit, enzyme-linked immunosorbent assay (ELISA) kit.
3.2 ulcerative colitis model and drug administration group
After 1 week of adaptive feeding of 126 male BALB/c mice, the mice were randomly divided into 21 groups (n=6) using the random number table method: a blank control group, a model group, a positive control (mesalamine) group and a clinopodium polycephalum drug low and high dose group (CE) high and low (800 (CEH), 200 (CEL) mg/kg/d) dose group of Clinopodium polycephalum total flavonoids (CF) high and low (800 (CFH), 200 (CFL) mg/kg/d) dose group of Clinopodium polycephalum total diterpenes (C.locomotive diterpenoids, CD) high and low (800 (CDH), 200 (CDL) mg/kg/d) dose group and Clinopodium polycephalum total triterpenes (C.locomotive Extract, CT) high and low (800 (CTH), 200 (CTL) mg/kg/d) dose group of monomeric compounds (Sascroll, SA) high and low (800 (SAH), 200 (SAL) mg/kg/d) dose group of cape total flavonoids (C.locomotive total diterpenoids), 200 (PEL) high and low (CDL) dose group of total triterpenes (C.locomotive total triterpenes, 200 (CPL) and 200 (CPL) total triterpenes (CPL) dose group of total triterpenes (C.locomotive total triterpenes, CT) high and 200 (CPL) dose group of Clinopodium polycephalum total triterpenes (C.C.locomotive Extract, CPE) high and low (CEH) dose group of Clinopodium polycephalum total flavonoids (C.CEL) and 200 (CEL) total flavonoids (CF) dose group of Clinopodium, 200 (PTL) mg/kg/d) dose group
The mice of the control group were given distilled water during the experiment, and the other groups were given a free drink of 4% dss aqueous solution for 7 consecutive days to induce UC mice model, all in an amount of 5 ml/mouse/day. The mice in each group were weighed and labeled for 7 days before and after continuous administration, and each group was then verified.
3.3 Disease Activity Index (DAI) assessment
The status of each group of mice was observed daily during the experiment, and the mice were subjected to DAI evaluation, specifically recording the weight change, fecal characteristics and fecal occult blood condition of each mouse. The scoring criteria are as follows: percentage of weight loss (0, 0;1% to 5%,1;5% to 10%,2;10% to 20%,3; > 20%, 4); fecal character (normal, 0; soft stool, 1; mucus-like stool, 2; thin liquid stool, 3); fecal occult blood (negative, 0, light blue, 1, blue, 2, dark blue, 3, macroscopic bloody stool, 4). Fecal occult blood test the urinary occult blood test kit (benzidine method) was used, and the DAI score was the sum of three indicators, see fig. 3 and 4.
To verify the therapeutic effect of clinopodium polycephalum extract on DSS-induced ulcerative colitis miceAccording to the application, DAI evaluation is carried out on mice through experiments, and the weight, fecal properties and occult blood conditions of the mice are examined. As can be seen from FIGS. 3 and 4, the mice in the DSS model group had significantly reduced body weight compared to the control group ### P is less than 0.001), and DAI score is obviously increased ### P < 0.001); compared with the model group, the positive drug group and each dose group UC mice show remarkable inhibiting weight loss (P < 0.001) and inhibiting DAI score rising effect (P < 0.001). The clinopodium polycephalum extract has the function of improving the DAI of ulcerative colitis mice, can effectively prevent and improve the pathological damage of intestinal tissues of the ulcerative colitis mice, and has remarkable anti-ulcerative colitis activity.
3.4 colon Length observations
Mice were sacrificed at the end of the experiment, the spleens of the mice were dissected and collected for weighing comparison. The entire colorectal was collected for colorectal morphology and the colon length was measured, see fig. 5.
As can be seen from fig. 5, the epithelium is intact in colon tissue sections of normal mice, and the crypt glands, stroma and submucosa structure are not disrupted. The mucous membrane structure of the model group mice is obviously destroyed, a large amount of ulcer areas exist, colon epithelium is thickened, colonic hypodermis oedema occurs, serious inflammatory cell infiltration occurs, and colonic tissues are seriously damaged. Compared with the modeling group, the colon length of the UC mice in the administration group is obviously prolonged, and the ulcer area is reduced. The colonic tissue structure condition is improved obviously. This indicates that the clinopodium polycephalum extract has the function of improving inflammatory pathological injury of the intestinal tissue of the mice, repairing ulcers and improving the reduction of colon length caused by ulcerative colitis.
3.5HE staining to observe colonic tissue morphology
Preparing a colon pathological tissue section of a mouse: colon tissue of each group of mice at least 6cm from anus was taken, fixed with 10% paraformaldehyde, dehydrated with ethanol gradient, paraffin-embedded, cut into slices with a thickness of 5 μm using a tissue slicer, and observed under an optical microscope for tissue morphology and inflammation severity with Hematoxylin Eosin (HE) staining, and scored. The scoring rules are as follows: 0, normal morphology, no inflammation; 1, mild inflammation, about 1/3 crypt destruction; 2, moderate inflammation, large area goblet cell loss; 3, crypt loss and extensive inflammatory infiltration of mucosal myolayers; 4, crypt and epithelial cells were lost, submucosal layers were extensively inflammatory infiltrated, see fig. 6.
As can be seen from fig. 6, the epithelium is intact in colon tissue sections of HE normal group mice, and the crypt glands, stroma and submucosa structure are not disrupted. The DSS model group showed severe inflammatory cell infiltration and severe damage to colon tissue. The tissue injury and inflammatory cell infiltration of the mice of the administration group are obviously improved. This suggests that each dose group of clinopodium polycephalum extract has the effects of improving colon tissue injury and reducing inflammatory reaction, and fully demonstrates the anti-inflammatory activity of clinopodium polycephalum.
3.6ELISA detection of inflammatory factor levels in plasma
And detecting the content of IL-6, TNF-alpha, INF-gamma and IL-4 in the plasma of each group of mice and the content of MDA and SOD in colon tissue homogenate by adopting an ELISA method according to a kit instruction.
IL-6 has strong pro-inflammatory activity and can induce a plurality of pro-inflammatory mediators. TNF- α is a pleiotropic pro-inflammatory cytokine and is involved in the development of a variety of diseases. In the case of inflammatory diseases, immune cells are usually preferentially selected to activate CD4 + Is a Th cell; IFN-gamma is a dominant cytokine for Th1 cells, th1 cells mediate cellular immunity, and IFN-gamma can promote polarization of T cells to Th1 and inhibit polarization to Th 2. IL-4 is a dominant cytokine for Th2 cells, and Th2 cells mainly mediate humoral immunity, and IL-4 can promote T cell polarization to Th2 and inhibit polarization to Th 1.
As can be seen from fig. 7 and 8, ELISA assays showed that: compared with the control group, the content of IL-6, TNF-alpha and INF-gamma in the plasma of the DSS modeling module is obviously improved ### P < 0.001), the positive drug group and each dose group had significantly reduced levels of proinflammatory cytokines compared to the model group (P < 0.001), and significantly increased levels of anti-inflammatory cytokine IL-4 (P < 0.001). This shows that the extract of Clinopodium polycephalum can obviously reduce IL-6, TNF-alpha and INF-gamma levels in blood plasma, reduce proinflammatory cytokine levels and raise anti-inflammatory cytokine levels, and this fully shows that the extract of Clinopodium polycephalum can regulate Th1 and Th2 by regulating the levels of cytokines with different actionsThe cell subgroup has balanced action, so that the immune system of the organism is recovered to normal action and expression.
ELISA (enzyme-Linked immuno sorbent assay) for detecting MDA (MDA) and SOD (superoxide dismutase) contents in colon tissue homogenate, and compared with a control group, the MDA content of mice in DSS (direct sequence) group is obviously reduced ### P is less than 0.001), and the SOD content is obviously reduced ### P < 0.001). Compared with the model group, the positive drug group and the colon tissue homogenate of the mice in each dose group have significantly increased MDA content (P < 0.001), and have significantly decreased SOD content (P < 0.001). The results show that the clinopodium polycephalum extract can obviously increase the MDA content in colon tissue homogenate and reduce the SOD content in colon tissue homogenate, thereby achieving the anti-inflammatory effect by adjusting the level of anti-inflammatory factors in vivo, relieving ulcer and treating ulcerative colitis.
Through the verification of the above five embodiments, it can be obtained that: the Clinopodium polycephalum herba Clinopodii extract has good anti-inflammatory activity, and can regulate and balance normal functions of organism immune system by regulating the content of various inflammation related cytokines such as TNF-alpha and IL-4 in vivo, and promote autoimmunity, thereby achieving therapeutic effect on ulcerative colitis. Meanwhile, the clinopodium polycephalum extract can also reduce inflammatory reaction and improve inflammatory injury of colon tissue structure by inhibiting NF- κB level. In addition, the anti-inflammatory agent can regulate the level of in vivo anti-inflammatory factors such as SOD and MDA, lighten inflammatory reaction of colonic mucosa tissues and play a role in protecting colonic mucosa. The clinopodium polycephalum has good application prospect for the treatment of ulcerative colitis.
Claims (8)
1. An application of herba Clinopodii in preparing medicine for treating ulcerative colitis is provided.
2. Use of clinopodium polycephalum according to claim 1 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the herba Clinopodii is dry aerial part or dry whole plant of Clinopodium polycephalum herba Clinopodii (Clinopodium chinense) or herba Begoniae Laciniatae (Clinopodium polycephalum) of Labiatae.
3. Use of clinopodium polycephalum according to claim 1 or 2 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the herba Clinopodii is herba Clinopodii extract.
4. Use of clinopodium polycephalum according to claim 3 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the herba Clinopodii extract is obtained by extracting dried aerial parts of herba Clinopodii and/or herba Physalis Pubescentis or dried whole plant with water or organic solvent.
5. Use of clinopodium polycephalum according to claim 4 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the herba Clinopodii extract contains one or more of total extract, total flavone, total diterpenoid and total triterpene extracted from herba Clinopodii and/or herba Physalis chinensis.
6. Use of clinopodium polycephalum according to claim 5 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the application of the monomer compound Sarurolide obtained by extracting from clinopodium polycephalum in preparing the medicine for treating ulcerative colitis.
7. Use of clinopodium polycephalum according to claims 1-6 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the extract, the effective parts and the monomers of the clinopodium polycephalum are taken as active ingredients, and the active ingredients and pharmaceutically acceptable carriers, auxiliary materials or pharmaceutically acceptable excipients form a pharmaceutical preparation.
8. Use of clinopodium polycephalum according to claim 7 for the preparation of a medicament for the treatment of ulcerative colitis, characterized in that: the dosage form of the pharmaceutical preparation is liquid dosage form, solid dosage form, semisolid dosage form, gas dosage form or enema.
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