CN110038007A - A kind of composition with improvement acute gastric mucosal injury effect - Google Patents
A kind of composition with improvement acute gastric mucosal injury effect Download PDFInfo
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- CN110038007A CN110038007A CN201811629266.7A CN201811629266A CN110038007A CN 110038007 A CN110038007 A CN 110038007A CN 201811629266 A CN201811629266 A CN 201811629266A CN 110038007 A CN110038007 A CN 110038007A
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- 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
- 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
Abstract
The present invention provides a kind of with the composition for improving acute gastric mucosal injury effect, it is made of costunolide and dehydro-α-curcumene, weight proportion are as follows: 3 parts of costunolide, 0.7~12 part of dehydro-α-curcumene.Composition of the invention can improve mucosal lesion, prevent acute gastric mucosal injury, and conspicuousness reduces mucosal lesion TNF-α, the level of NF-kB, NO, iNOS and MDA, and conspicuousness increased SOD and PCNA are horizontal, promote mucosa ulcer healing.When composition proportion compatibility is 3:1, all extremely obvious (p ﹤ 0.001) is influenced on the horizontal of proinflammatory inflammation factor, NO, iNOS, Oxidative Stress and PCNA, the composition has good application prospect.
Description
Technical field
Present invention relates particularly to a kind of with the composition for improving acute gastric mucosal injury effect.
Background technique
Mucosal lesion is chemical factor: smoke, drink, strong tea, coffee and stimulate stomach lining drug such as aspirin,
Indocin etc., physical factor: supercooling, excessively boiling hot, excessively coarse food or overeating etc., the factors such as bacterium or the stimulation of its toxin
Caused stomach lining bleeding, hyperemia and rotten to the corn damage.No matter which kind of invades factor, and caused mucosal lesion is shown as
The injury response of sequencing: being that falling off for surface epithelium generates shallow mucosa injury first;Damage further development, capilary
Endothelial cell damage will lead to mucous membrane ischemic, anoxic, tissue necrosis, so that depth mucosa injury occur: rotten to the corn or ulcer.It is acute
Mucosal lesion is existing studies have shown that: alcoholic drink again with most commonly seen caused by alcohol, as beer and grape wine can stimulate
The release of gastrin, increasing for gastrin content accelerates gastric acid secretion, so as to cause acute gastric mucosal injury.
Radix aucklandiae is the root of compositae plant radix aucklandiae Aucklandia lappa Decne., cylindrical or flat round cylindricality.Surface is yellow
Brown, taupe or sepia, cork have removed mostly, have bright longitudinal furrow and lateral root trace, sometimes visible reticular texture.Gas fragrance is dense
It is strong and special, it is bitter after taste elder generation sweet tea, slightly pierce tongue.Traditional medicine thinks that radix aucklandiae has effects that promoting qi circulation and relieving pain, can significantly increase stomach and intestine and push away
Into movement, relaxing smooth muscle, spasmolysis and cholagogue, it is chiefly used in abdominal distention caused by the stomach and intestine stagnation of the circulation of vital energy, inverse eat less or for damp and hot of vomitting
It is the abdominal pain of dysentery, tenesmus.Radix jurineae is compositae plant radix jurineae Vladimiria souliei (Franch.) Ling or ash
The dry root of hair radix jurineae Vladimiria souliei (Franch.) Ling var.cinerea Ling, cylindrical or semicircle
Cylindricality.Surface yellowish-brown or sepia have vertical wrinkle, and crust, which falls off, locates the visible thin tendon and vessel of luffa shape;Root head occasionally has black hair
Glutinous jelly is practised and claims " oil head ";There is radial texture, some centers are in dry and decayed shape.Gas micro-perfume, bitter, that chews sticks to one's teeth.River wood
Perfume also has the benefits of promoting qi circulation and relieving pain, can be used for chest side of body, abdominal distention, borborygmus diarrhea is tenesmus, clinically primary treatment stomach
The relevant disease of enteron aisle, including gastritis and gastric ulcer.Costunolide and dehydro-α-curcumene are in radix aucklandiae and radix jurineae medicinal material
Main effective ingredient, belong to sesquiterpenoids, modern pharmacological studies have shown that both compounds and containing both
The Radix Aucklandiae extract of compound all has anti-gastric-ulcer, anticancer, anti-inflammatory, antibacterial and bactericidal effect.Dong's book radix aucklandiae principal component contains
Measure fixed and its Beijing pharmacokinetic [D]: Beijing University of Chemical Technology, 2012:1-63. pass through mouse Pharmacokinetic experiments
Research compares Radix Aucklandiae extract and the intracorporal absorption behavior of monomer drug combination (blood-concentration and bioavilability), from one
Aspect shows the difference of monomer and extract blood concentration, bioavilability etc., but the complicated component in Radix Aucklandiae extract,
It can not only illustrate the medical value of radix aucklandiae class drug from pharmacokinetics angle, specific drug effect difference is simultaneously indefinite.
Summary of the invention
For the medical value for further developing and using clinical common medicine radix aucklandiae and Genuine crude drugs in Sichuan radix jurineae, the present invention is mentioned
A kind of composition with improvement acute gastric mucosal injury effect is supplied, it is by costunolide and dehydro-α-curcumene group
At weight proportion are as follows: 3 parts of costunolide, 0.7~12 part of dehydro-α-curcumene.
Further, the weight proportion of the costunolide and dehydro-α-curcumene are as follows: 3 parts of costunolide, go
1 part of hydrogen constuslactone.
The present invention also provides a kind of purposes of aforementioned composition in the drug that preparation improves mucosal lesion.
Further, the drug is the drug for preventing mucosal lesion.
Further, the drug is the drug for preventing acute gastric mucosal injury.
Further, the drug is the drug of acute gastric mucosal injury caused by preventing alcohol.
Further, the drug is to reduce inflammation-associated cytokine TNF-α, the drug of NF-kB.
Further, the drug is the drug for reducing lipid peroxidation product MDA.
Further, the drug is the drug for increasing antioxidase SOD.
Further, the drug is the drug for reducing NO.
Further, the drug is the drug for reducing nitric oxide synthase type iNOS.
Further, the drug is the drug for increasing proliferating cell nuclear antigen PCNA.
Composition of the invention can improve mucosal lesion, prevent acute gastric mucosal injury, reduce mucosal lesion TNF-
The level of α, NF-kB, NO, iNOS and MDA, conspicuousness increased SOD and PCNA are horizontal, promote mucosa ulcer healing.Work as composition
When proportion compatibility is 3:1, the horizontal of proinflammatory inflammation factor, NO, iNOS, Oxidative Stress and PCNA is influenced all extremely obviously
(p ﹤ 0.001), the composition has good application prospect.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Detailed description of the invention
Gastric tissue pathologic condition (a: blank control, b: model, the c: positive control, d:CO (radix aucklandiae of Fig. 1 gastric ulcer mouse
Hydrocarbon lactone), e:DE (dehydro-α-curcumene), f:CO:DE=1:1, g:CO:DE=1:2, h:CO:DE=1:3, i:CO:DE=
1:4, j:CO:DE=2:1, k:CO:DE=3:1, i:CO:DE=4:1).
Fig. 2 gastric ulcer mouse histopathology situation (A: blank control, B: model group, C: positive control, D:CO, E:DE,
F:CO:DE=1:1, G:CO:DE=1:2, H:CO:DE=1:3, I:CO:DE=1:4, J:CO:DE=2:1, K:CO:DE=3:
1, L:CO:DE=4:1, amplification factor 100).
Fig. 3 CO, DE and each compatibility group (CO:DE) to TNF-α and NF-kB in ethyl alcohol gastric ulcer Mice Body influence (A:
TNF-α, B:NF-kB, model group compared to the blank group, #P < 0.05, ##P < 0.01, ###P < 0.001;Each administration group and model
Group is compared, P < 0.001 * P < 0.05, * * P < 0.01, * * *).
Fig. 4 CO, DE and each compatibility group (CO:DE) to MDA and SOD content in ethyl alcohol gastric ulcer Mice Body influence (A:
MDA, B:SOD, model group compared to the blank group, #P < 0.05, ##P < 0.01, ###P < 0.001;Each administration group and model group phase
Than P < 0.001 * P < 0.05, * * P < 0.01, * * *).
The shadow of Fig. 5 CO, DE and each compatibility group (CO:DE) to iNOS content in NO in ethyl alcohol gastric ulcer Mice Body and gastric tissue
Ring (A:NO, B:iNOS, model group compared to the blank group, #P < 0.05, ##P < 0.01, ###P < 0.001;Each administration group and model
Group is compared, P < 0.001 * P < 0.05, * * P < 0.01, * * *).
Influence (the model of Fig. 6 CO, DE and each compatibility group (CO:DE) to PCNA content in ethyl alcohol gastric ulcer mouse gastric tissue
It organizes compared to the blank group, #P < 0.05, ##P < 0.01, ###P < 0.001;Each administration group compared with model group, * P < 0.05, * * P <
0.01, * P < 0.001 * *).
Specific embodiment
1 present composition of embodiment
It takes costunolide (CO) 96mg, dehydro-α-curcumene (DE) 32mg to be uniformly mixed, obtains the group of CO:DE=3:1
Close object.
2 present composition of embodiment
It takes costunolide (CO) 96mg, dehydro-α-curcumene (DE) 24mg to be uniformly mixed, obtains CO:DE=3:0.75's
Composition.
3 present composition of embodiment
It takes costunolide (CO) 96mg, dehydro-α-curcumene (DE) 384mg to be uniformly mixed, obtains CO:DE=3:12's
Composition.
Beneficial effects of the present invention are proved below by way of specific test example:
1 experimental material
1.1 instrument
Air-cooled centrifuge (Select BioProducts, USA);
UPT-II-10T type Superpure water machine (Chengdu Ultra Pure Science & Technology Co., Ltd);
Low temperature refrigerator (Haier);
FSH-2A type is adjustable high speed refiner (Changzhou Guo Wang instrument manufacturing Co., Ltd);
FA2004N type electronic balance (Shanghai Precision Scientific Apparatus Co., Ltd).
352 type microplate reader (Finland Labsystems Multiskan MS)
1.2 experimental animal
Kunming male mice, weight 18-22g, not used any drug before testing reach the limited public affairs of large experimental animal by Chengdu
Department provides, production licence number: SCXK (river) 2015-030.
Animal is 22~26 DEG C, adapts to raise for one week in the alternate environment of 12/12h daytime rule in temperature, gives grinding tooth
Class animal diet followed and free water.
1.3 reagent and reagent
Costunolide (purity: HPLC > 98%, CAS:533-21-9);Dehydro-α-curcumene (purity: HPLC > 98%,
CAS:477-43-0), it is purchased from Chengdu Rui Sifen Biotechnology Co., Ltd;4% paraformaldehyde solution (lot number: LOT:
180321, Foochow Fei Jing Biotechnology Co., Ltd);PBS buffer solution (lot number: Lot No.:AC13298279, the U.S.
HyClone company);Ethyl alcohol (lot number: CAS:64-17-5), Tween-80 (lot number: 2015042801) are purchased from Chengdu section dragon reagent
Factory;TNF-α kit, NF-kB kit, SOD kit, MDA kit, NO kit, iNOS kit, PCNA reagent
Box is purchased from Shanghai Ying Gong Biotechnology Co., Ltd.
Improvement result of 1 present composition of test example to acute gastric mucosal injury rat
(1) experimental program
1.1, the selection of CO and DE dosage
Version " Chinese Pharmacopoeia " radix jurineae in 2015 is calculated by dry product, total containing costunolide and dehydro-α-curcumene
Amount must not be less than 3.2%, and the dosage that instructs of medicinal material is 3-9g.It selects to imitate dosage 6g in quantity to be dosage, according to mouse
With people's conversion method, mouse dose is obtained are as follows: 19.7mg/kg.
1.2, influence of the different proportion CO and DE to dehydrated alcohol institute Ulceration
Mouse 96 are taken, normal group, model group, positive controls (Cimetidine-CIM 80mg/kg), CO are randomly divided into
Group (19.7mg/kg), DE group (19.7mg/kg), CO:DE=1:1 (weight ratio, rear same), CO:DE=1:2, CO:DE=1:3,
CO:DE=1:4, CO:DE=2:1, CO:DE=3:1, CO:DE=4:1.Preparatory gastric infusion 7 days, blank group and model group were given
The same amount of solvent of medicine (2% Tween-80).Fasting is for 24 hours, except for the normal group, every small after last dose 30min before modeling
Mouse stomach-filling dehydrated alcohol (0.1ml/10g) sets up chmice acute gastric ulcer model after 1h, after eye socket takes blood, takes out mouse
Stomach observes effect of the different proportion CO and DE to acute ethanol mucosal lesion.
1.3 ulcer inhibition rate
Gastric tissue is cut off along greater curvature, it is clean with ice normal saline flushing, it observes and calculates ulcer index.Without canker
Change is calculated as 0 point, and ulcer length of lesion < 1mm=1 points, ulcer length of lesion 1-2mm=2 divides, ulcer length of lesion 2-3mm=3
Point, ulcer length of lesion 3-4mm=4 points, ulcer length of lesion > 4 are 5 points.Ulcer inhibition rate (%)=(UI model group-UI is real
Test group)/UI model group × 100%.
The acquisition and processing of 1.4 blood serum sample stomach function regulating tissue samples
Mouse orbit takes blood, is placed in plastic centrifuge tube, is stored at room temperature 30min, is centrifuged (4500rpm, 10min), takes
Clear liquid, it is to be measured under the conditions of being placed in -80 DEG C.After the completion of taking blood, the neck that breaks puts to death animal, takes out gastric tissue immediately, cuts off along greater curvature,
Blood stains, weighed weight are washed down with ice physiological saline.PBS solution is added with the ratio of 1:9, it is low after being handled using tissue refiner
Temperature centrifugation (4500rpm, 10
Min), supernatant is taken, it is to be measured under the conditions of being placed in -80 DEG C.
1.5HE dyeing
The gastric tissue of acquisition is placed in 4% paraformaldehyde solution, is saved at room temperature.Through tissue repair cut, paraffin embedding, routine
After slice, HE dyeing, alcohol serial dehydration, transparent, mounting, (× 100, × 200) are observed under optical microscopy.
1.6 biochemical analysis
With enzyme linked immunosorbent assay (ELISA kit) measurement gastric tissue in proliferating cell nuclear antigen (PCNA) and
The level of nitric oxide synthase type (iNOS);Oxidative stress index in serum: superoxide dismutase (SOD) and malonaldehyde
(MDA);Inflammation-associated cytokine: Nuclear-factor kappa B (NF-kB), tumor necrosis factor-alpha (TNF-α) and nitric oxide
(NO), and statistical analysis is carried out to result.
1.7 data processing and inversion
Experiment carries out single factor test point with SPSS18.0 software using the method for Multiple range test between variance analysis and mean
Analysis.
(2) analysis of experimental results and discussion
2.1 ulcer indexes and ulcer inhibition rate
After giving alcohol induced gastric ulcer, ulcer index and ulcer lesion can be obviously increased, mucosa injury bleeding is caused.
After giving CO, DE and various dose compatibility (CO:DE) treatment, it can be effectively improved mucosa injury caused by ethyl alcohol, reduce and burst
Ulcer index, (being shown in Table 1).
1 different proportion CO and DE mouse gastric ulcer index of table and ulcer inhibition rate variation
Note: compared with model group, P < 0.01 * *
2.2 mouse gastric tissue macroscopic analyses and Histopathology evaluation
After Mouse oral dehydrated alcohol 1h, gastric mucosa tissue can be caused obviously to damage and bleeding (see the b of Fig. 1), given in advance
Positive drug Cimetidine, CO, DE and various dose compatibility (CO:DE) can be effectively improved caused by dehydrated alcohol after a week and stick
Membrane damage (see the c-i of Fig. 1).Mouse Stomach histopathologic change result is shown in Fig. 2, gives alcohol induced acute gastric ulcer (see Fig. 2's
B), it is seen that gastric tissue cellular morphology obviously changes, and arranges loose;Gastric mucosa layer visible cell falls off, capillary extravasated blood,
Mucous layer bottom and the visible massive inflammatory cells infiltrated of submucosa;Submucosa oedema, gap is broadening, connective tissue loose;
Giving positive drug Cimetidine, CO, DE and various dose compatibility (CO:DE), visible gastric tissue damage and inflammation obtain afterwards
Alleviate, submucosa inflammatory cell infiltration reduce, epithelial cell form be improved significantly, mucous layer gastric gland arrangement it is more tight
It is close;Submucosa oedema, connective tissue loose are also significantly improved compared with model group (see the C-L of Fig. 2) simultaneously.
Influence of the 2.3 various dose compatibility CO and DE to the relevant cell factor of inflammation
TNF-α in mice serum (P < 0.001, Fig. 3 A), NF-kB can be dramatically increased compared with blank group, after stomach-filling ethyl alcohol
The level of (P < 0.001, Fig. 3 B), give CO, DE and various dose compatibility (CO:DE) can reduce in Mice Body proinflammatory disease because
It is sub horizontal.TNF-α is inflammatory cytokine, participates in systemic inflammatory response, is a kind of endogenous pyrogen, can cause to generate heat,
It induces cell apoptosis, and the generation of inflammatory factor and superoxide anion can be promoted.It is as shown in Figure 3A: to give positive drug west
Miaow is decreased obviously for visible TNF-α level after fourth, CO, DE and various dose compatibility, has significant difference, wherein 1:2 and
TNF-α level is declined compared with model group in 1:3, but unknown significance difference, and TNF-α is horizontal when CO:DE compatibility dosage is 3:1
Decline is the most significant (P < 0.001), and close to normal level, also more independent pre-administration CO, DE influences TNF-α level bigger.
NF-kB participates in the early stage and inflammatory reaction each stage of regulation immune response, is usually present in cytoplasm with inactive state,
It is activated under a variety of inflammatory cytokines and the effect of other stimulin, and rich poly- into nucleus, the regulating cell factor, chemotactic
The isogenic expression of the factor, growth factor, adhesion molecule, and then influence that machine is intracorporal congenital or the acquired immune response, inflammation
The multiple biological functions such as property reaction, cell differentiation, Apoptosis, tumour growth.It is as shown in Figure 3B: to give CO, DE and not
NF-kB content is substantially reduced same dose compatibility (CO:DE) afterwards, and wherein CO, DE, 1:2,1:4,3:1,4:1 decline are fairly obvious,
With significant difference (P < 0.001), 1:1 group NF-kB content, which reduces, also has conspicuousness (P < 0.01), 1:3 and 2:1 group NF-
KB content is declined slightly, but unknown significance (P > 0.05).CO and CO:DE compatibility is that the decline of 3:1,4:1 group is the most obvious.
Influence of the 2.4 various dose compatibility CO and DE to oxidative stress index
MDA is the final metabolite of lipid peroxidation, and excessive MDA can cause a series of cytotoxic effect, add
The damage of acute film, therefore the quantity that MDA is generated can represent Lipid peroxidation metabolism degree, be an index ingredient.Experimental result
It can be seen that (Fig. 4 A), the horizontal significant raising of oxidative stress index MDA in gastric ulcer model caused by ethyl alcohol, with blank group phase
Than having significant difference (P < 0.001).Give CO, DE, 1:1,1:3,3:1,4:1 treatment after can reduce it is alcohol induced
MDA content in gastric ulcer Mice Body, wherein CO, 1:3 and 3:1 group have extremely significant sex differernce (P < 0.001), DE group (P <
0.01), 4:1 group (P < 0.05) has significant difference compared with model group, and 1:1 group MDA content is declined, but unknown significance
Difference (P > 0.05), while CO, 1:3,3:1 group, relatively with other administration groups, MDA content reduces the most obvious.
SOD by scavenging activated oxygen, reduces superoxide anion and forms the as the intracorporal preventative antioxidase of biology
Body damage is protected in one of defence line.The activity of oxygen free radical scavenger SOD reduces, it will leads to the product of activity in vivo oxygen
It is tired, promote the metabolism of lipid peroxidation approach to generate a large amount of Peroxidation Product, oxidative damage is caused to body.With blank group phase
Than model group SOD content conspicuousness reduces (P < 0.001), and it is small that 1:4,2:1,3:1,4:1 group increase alcohol induced gastric ulcer
SOD content in mouse body, wherein with extremely significant sex differernce (P < 0.001) compared with model group, 4:1 group has significant 1:4 and 3:1
Sex differernce (P<0.01), although 2:1 group SOD content is increased, compared with model group, otherness is unobvious (P>0.05).
CO and DE, which is administered alone, reduces SOD content, after compatibility (1:4,3:1,4:1) can conspicuousness increased SOD it is horizontal,
And 3:1 group, relatively with other administration groups, SOD content increases the most obvious.
Influence of the 2.5 various dose compatibility CO and DE to NO and iNOS level
As a kind of important gaseous signal molecule, each in alcohol induced mucosal lesion plays NO in the process
Important adjustment effect.It is caused in mucosal lesion in ethyl alcohol, internal NO content steeply rises, and is likely due to ethyl alcohol and causes
Internal inflammatory mediator, inflammatory cell or content of oxygen free radical increase.It is as shown in Figure 5A: alcohol induced mouse gastric ulcer serum
In, compared to the blank group, the content conspicuousness of NO increases (P < 0.001) to model group, and pre-administration group is compared with model group, NO content drop
Low, wherein the extremely significant property of CO, 1:4,3:1,4:1 group NO content reduces (P < 0.001), the reduction of 2:1 group NO content conspicuousness (P <
0.01), 1:3 group NO content is declined, unknown significance difference (P > 0.05).Meanwhile DE is individually given on the influence of NO content
It shows unobvious;Relatively with other administration groups, NO content reduces the most obvious 3:1 and 1:4 group.Internal NOS has structural type NOS
(cNOS) and 2 kinds of induced NOS (iNOS), the former congenital presence, generates NO negligible amounts, generates rapid;The latter is in physiology
In the case of do not express substantially, when by certain cell factors, pathogenic microorganism or tumour cell stimulate after, _ be activated, largely
INOS is generated, and the duration is long.Wherein, the NO of cNOS catalysis shields to mucous membrane, and the NO of iNOS catalysis is to glutinous
Film has killing toxicity and pro-inflammatory effect.Experiment is found, in alcohol induced mouse gastric ulcer gastric tissue, model group and blank group phase
Content conspicuousness than, iNOS increases (P < 0.001), wherein giving CO, DE, 1:1,1:2,1:3,1:4,2:1,3:1 can be with
Reduce mouse gastric tissue in iNOS content, 1:1,1:3,2:1,3:1 with model group compared with extremely significant sex differernce (P <
0.001), 1:4 has significant difference (P < 0.01) compared with model group.Individually giving CO and DE influences not iNOS level
Obviously, it after CO and DE compatibility, is affected to iNOS level, while 3:1 group, relatively with other administration groups, the reduction of iNOS content is most
It is obvious.
The influence of 2.6 various dose compatibility CO and DE cell proliferation PCNA
PCNA is the early signal of gastrointestinal tract epithelial cell functional disturbance, for evaluating the proliferation energy of gastric epithelial cells
An important factor for power is Mucous rehabilitation, ulcer healing.As seen from Figure 6: compared to the blank group, model group PCNA content conspicuousness
It reduces (P < 0.001), CO, DE decrease or increase to PCNA, but show unobvious.Giving CO:DE compatibility dosage is that 3:1 can
Increase the level (P < 0.01) of PCNA in alcohol induced mouse gastric ulcer gastric tissue with conspicuousness, promote ulcer healing, and gives
It is more obvious on the reduction influence of PCNA level to give other compatibility dosage (CO:DE).
From the point of view of composition is to the protective effect of acute gastric ulcer rat: CO, DE and each compatibility (CO:DE) can subtract
Light alcohol induced mucosal lesion, macroscopic view and Histopathology assessment can confirm.Inflammation is alcohol induced stomach lining
One key mechanism of damage, it is horizontal that administration group can reduce proinflammatory inflammation factor TNF-α in Mice Body, NF-kB, while working as CO:
Two kinds of cytokine levels relevant to inflammation are influenced when DE compatibility is 3:1 all extremely obvious.NO is in inflammation and immune response
In play crucial adjustment effect, the process of inflammatory reaction can be influenced, such as influence the signal transduction pathway that NF-kB is relied on,
INOS can be catalyzed the generation of NO, have killing toxicity and pro-inflammatory effect, administration group that can reduce the water of NO and iNOS stomach lining
Flat, influence when wherein CO:DE compatibility is 3:1 to two kinds of factor levels of NO and iNOS is also the most significant.Stomach lining caused by ethyl alcohol
The pathogenesis of damage is usually very complicated, and wherein oxidative stress and exhausting for antioxidant are considered as the damage of stomach lining caused by ethyl alcohol
The committed step of wound.MDA is the primary product of polyunsaturated fatty acid peroxidating and the biomarker of oxidative stress, SOD
The important anti-oxidative defense object being accredited as in nearly all living cells for being exposed to oxygen.In alcohol induced mucosal lesion
In model, MDA level is increased, and SOD is reduced, and administration group may have dual regulation to MDA and SOD level, wherein CO,
DE is administered alone can reduce MDA level with part compatibility group with conspicuousness, and proportion compatibility is that 1:2,1:4,2:1 are shown as
It is horizontal that conspicuousness increases MDA;But the level of administration group ability conspicuousness increased SOD after compatibility, CO, DE, which are administered alone, to drop
Low SOD is horizontal, while can reduce MDA level with conspicuousness when CO:DE compatibility is 3:1, and increased SOD is horizontal, and relative to it
His administration group is more obvious.PCNA can promote Mucous rehabilitation and ulcer healing, and model group PCNA level reduces, administration group pair
PCNA level may also have a dual regulation, but only compatibility administration and when proportion compatibility is 3:1 could conspicuousness raising
PCNA is horizontal, be administered alone reduce or increase with other compatibility groups it is unobvious.
To sum up, CO and DE composition administration can reduce TNF-α, the level of NF-kB, NO, iNOS and MDA, compared with CO, DE
It is horizontal to be administered alone ability conspicuousness increased SOD and PCNA after composition is administered, promotion ulcer healing, while when composition is matched
When 5 ratios are 3:1, the horizontal of proinflammatory inflammation factor, NO, iNOS, Oxidative Stress and PCNA is influenced all extremely obviously.
Claims (10)
1. a kind of with the composition for improving acute gastric mucosal injury effect, it is by costunolide and dehydro-α-curcumene group
At weight proportion are as follows: 3 parts of costunolide, 0.7~12 part of dehydro-α-curcumene.
2. composition according to claim 1, it is characterised in that: the weight of the costunolide and dehydro-α-curcumene
Amount proportion are as follows: 3 parts of costunolide, 1 part of dehydro-α-curcumene.
3. purposes of the composition of any of claims 1 or 2 in the drug that preparation improves mucosal lesion.
4. purposes according to claim 3, it is characterised in that: the drug is the drug for preventing mucosal lesion.
5. purposes according to claim 4, it is characterised in that: the drug is the medicine for preventing acute gastric mucosal injury
Object;Preferably prevent the drug of acute gastric mucosal injury caused by alcohol.
6. purposes according to claim 3, it is characterised in that: the drug is to reduce inflammation-related factor TNF-α,
The drug of NF-kB.
7. purposes according to claim 3, it is characterised in that: the drug is to reduce lipid peroxidation product MDA
Drug.
8. purposes according to claim 3, it is characterised in that: the drug is the drug for increasing antioxidase SOD.
9. purposes according to claim 3, it is characterised in that: the drug is the drug for reducing NO.
10. purposes according to claim 3, it is characterised in that: the drug is to reduce nitric oxide synthase type
The drug of iNOS;And/or the drug is the drug for increasing proliferating cell nuclear antigen PCNA.
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CN114392337B (en) * | 2021-12-30 | 2023-04-25 | 汤臣倍健股份有限公司 | Composition with auxiliary protection function on gastric mucosa injury and application thereof |
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