CN106668034A - Application of L-fucose in medicines and health-care products for treating gastrointestinal lesions - Google Patents
Application of L-fucose in medicines and health-care products for treating gastrointestinal lesions Download PDFInfo
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- CN106668034A CN106668034A CN201710025866.1A CN201710025866A CN106668034A CN 106668034 A CN106668034 A CN 106668034A CN 201710025866 A CN201710025866 A CN 201710025866A CN 106668034 A CN106668034 A CN 106668034A
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- fucose
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 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
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of L-fucose in medicines and health-care products for treating gastrointestinal lesions. The L-fucose is used for treating the gastrointestinal lesions, such as inflammatory bowel disease, functional gastrointestinal disorder and irritable bowel syndrome. The medicine is a carbohydrate medicine, since the adverse effect is less, and the tolerance of a patient is good, so that the medicine can be widely applied into clinic. The medicine has the advantages that the L-fucose is used in an early period of the gastrointestinal lesions, the activation of mesenteric lymph node Treg cells is regulated by DC cells, the differentiation potential of colons Th1 and Th17 is inhibited, the generation of bile acid is inhibited by regulating the intestinal flora, the function of inhibiting the contraction and spasm of intestinal muscles is realized by an nNOS path, the intestinal inflammation and weight-losing conditions are improved, and the patient can obtain an obvious long-term prognosis benefit; because of limitations of related existing therapy medicines, namely multiple medicine types, large side effect and poor compliance, a new therapy strategy for treating the patients with the gastrointestinal lesions, such as the inflammatory bowel disease, the functional gastrointestinal disorder and the irritable bowel syndrome, is provided.
Description
Technical field
The present invention relates to treat Alimentary tract disease field, in particular to a kind of L-fucose in the medicine of Alimentary tract disease and
Apply in health product.
Background technology
Alimentary tract disease (Gastrointestinal Lesions, disease code：K92.902, phonetic code：XHDBB) it is
The important component part of human diseasess spectrum, comprising various diseases such as functional gastrointestinal disorder, inflammatory bowel, because of its high incidence and right
Quality of life heavy damage becomes the Tough questions of long-term threat various countries' human health.Wherein, intestinal caused after Alimentary tract disease
The weight loss that reconciles in road changing function, inflammation causes many patients ' life qualities to decline and or even the lethal main original that disables
Cause.Numerous studies find, function of intestinal canal after Alimentary tract disease changes, the weight loss that reconciles in inflammation be related to immunity of organism,
The multifactorial regulation and control such as digestive tract power, intestinal microbial population affect, and the destruction to above-mentioned multifactor balance can increase the state of an illness and appropriate
Regulation and control can be conducive to the balance between above-mentioned factor, and the recovery for balancing is then to improve patient's long-term prognosis deciding factor.
Nowadays, to mediation weight loss corresponding treatment curative effect on Alimentary tract disease and its related function of intestinal canal change, inflammation
It is still undesirable.The past traditional treatment is relative to be limited to, such as using Loperamide Hydrochloride diarrhea for diarrhoea, hydrocortisone etc.
Glucocorticoid processes autoimmune disorder, bacillus subtilis. the intestinal preparation for treating intestinal such as enterococcus bigeminy viable bacteria enteric coated capsule
Road Flora Disturbance, it has large side effects, and patient medication is more, cures from drawbacks such as property differences.And enteral nutrition is treatment digestive tract disease
Change receives the treatment meanss of attention further.Research has shown that enteral nutrition additionally aids intestinal and glue in addition to acting on except nutritional support
Theca cell structure and the integrity of function, keep the stable state of gastrointestinal bacterial flora, prevent the generation of bacterial translocation.On the other hand, intestinal
Interior nutrition makes nutrient metabolism more conform to physiology, is conducive to synthesis and the Metabolism regulation of the protein of internal organs；Enteral nutrition
Adjust System immunity and physiological function are may also participate in, the generation of organ dysfunction is reduced.Meanwhile, by substantial amounts of evidence-based medicine EBM
Evidence show further their applications in Alimentary tract disease clinical treatment.But wherein various components outside Nutrition
Pharmacological action it is how indefinite.
L-fucose as food in monosaccharide common in (especially Sargassum), its medical value to Alimentary tract disease is simultaneously
It is not clear and definite.Research at present thinks that it is close with maintaining the relationship for intestinal stable state, such as the researcher of Tokyo University and Chicago University
It was found that knowing from experience the expression of rise enteric epithelium fucose to support the existence of fungal component to maintain intestinal when there is systemic inflammatory response opportunity
Road stable state.And fucose itself is used as one of the constituent of human milk oligosaccharides (HMO), its heavy dose of oral safety is also obtained
Checking.Additionally, another research then points out it to have the effect for suppressing pathogen adhesion and virulence.
The content of the invention
It is an object of the invention to provide a kind of L-fucose is applied in the medicine of Alimentary tract disease, which solve existing
Treatment high side effect in Alimentary tract disease long-term prognosis are improved, the defect of low effect.
For achieving the above object, a kind of medicine and health product of the L-fucose that the present invention is provided in treatment Alimentary tract disease
Middle application.
L-fucose (L-Fucose, chemical formula C6H12O5) it is a kind of deoxyhexamethylose.It is common in mammal, insecticide
It is rock algae base with the O-shaped-connection polysaccharide in the N-type of surface of Plant callus cell-connection polysaccharide and mammalian gut mucus and epithelium
The basis subunit of polysaccharide polysaccharide.L-fucose can be by being referred to as the enzyme of Alpha-Fucosidase from the polymer containing fucose
Release., used as gut epithelium and the glycosylated important component part of mucus, it is to intestinal microbial population and the regulation and control of immunity for L-fucose
Effect reported by multinomial high-quality institute, for example, it has been found that L-fucose baseization can to reduce antibody thin with NK cell
Born of the same parents' Fc receptor bindings, so as to lower antigen-dependent cytotoxity, thus can be by adjusting core fucosylation enzyme (FUT8)
Body cell is affected to kill ability.Regrettably, although experiment interior emerges be related in a large number fucose impact Alimentary tract disease
Evidence, it is removed outside as disease observation index in clinical effect, and the effect in terms for the treatment of Alimentary tract disease has no report
Road.
L-fucose is applied to the treatment of Alimentary tract disease.First, experimental group specify that by intestinal pathological changes animal model
L-fucose can make it obtain significant long-term prognosis benefit.Secondly, L-fucose can pass through DC cells in terms of immunoregulation
Regulation and control mesenteric lymph node Treg cell activations, suppress the potential of colon T h1 and Th17 differentiation.On the other hand, L-fucose can
The generation of bile acid by the regulation to intestinal microbial population, can be suppressed to reduce inflammation reaction.Finally, we specify that L-fucose leads to
Crossing nNOS approach suppresses intestinal muscle to shrink the effect of spasm, can finally mitigate the symptom of abdominal pain diarrhea.
In sum, L-fucose regulates and controls intestinal Treg cell activations by adjusting body DC cellullar immunologic responses, adjusts
Intestinal microbial population bile acid is generated, while L-fucose can suppress intestinal muscle to shrink spasm by adjusting nNOS.
Present invention also offers a kind of medicine or health-care preparation for treating Alimentary tract disease, the preparation includes L- rock algaes
Sugar.Wherein, medicine or health-care preparation are oral formulations.Oral formulations are tablet, capsule or granule.
The beneficial effects of the present invention is：
When Alimentary tract disease occurs, the L-fucose of the present invention is given birth to by adjusting immunity of organism, intestinal microbial population and muscle
Reason, and then the state of an illness such as inflammation damnification and diarrhoea is reduced, it is final to reduce related clinical adverse events (the body weight mistake of Alimentary tract disease
Gently, it is dead) incidence rate.
Description of the drawings
Fig. 1 is the trendgram that L-fucose intervenes the change of DSS chronic colitiss Mouse Weight；
Fig. 2 is the trendgram of the body weight change that L-fucose intervenes DSS acute colitis mices,
Fig. 2A is each group mouse disease activity index figure,
Fig. 2 B are each group Mouse Weight rate of change figure,
Fig. 2 C are each group mouse Colon length vs figure,
Fig. 2 D are each group mouse Colon pathological change figure；
Fig. 3 is that L-fucose regulates and controls situation map to dendritic cell,
Fig. 3 A are that L-fucose intervenes DSS inducing acute colitis mice, to DC hypotypes in colon and mesenteric lymph node
Regulation and control figure,
Fig. 3 B are L-fucose direct intervention DC2.4 cells, can activate the variation diagram of different effect factor expression downstream；
Fig. 4 is action diagram of the L-fucose to intestinal flora metabolism,
Fig. 4 A are that L-fucose intervenes acute DSS inductions enteritis mouse ileum intestinal contentses pH value,
Fig. 4 B are ileal contents metabolite LC-MS analysis figure；
Fig. 5 is impact figure of the L-fucose to the Spontaneous Contraction of Isolated colon smooth muscle
Fig. 5 A act on rat lower distal colon longitudinal muscle smooth muscle contractile activity figure for control sucrose,
Fig. 5 B act on rat lower distal colon longitudinal muscle smooth muscle contractile activity figure for L-fucose,
Fig. 5 C act on rat proximal colon longitudinal muscle smooth muscle contractile activity figure for L-fucose,
Fig. 5 D act on people's colon longitudinal muscle smooth muscle contractile activity figure for L-fucose sugar,
Fig. 5 E are L-fucose (control sucrose) to people and the impact figure of rat colon smooth muscle；
Fig. 6 is impact figure of the L-fucose to rat colon smooth muscle under spasticity；
Fig. 6 A are the impact figure (L-fucose) after (control sucrose) Ach stimulations to rat lower distal colon longitudinal muscle bar,
Fig. 6 B are the impact figure (control sucrose) after the stimulation of control sucrose Ach to rat lower distal colon longitudinal muscle bar；
Fig. 7 is the mechanism choice that L-fucose suppresses Isolated colon longitudinal muscle Spontaneous Contraction,
Fig. 7 A give variable concentrations fucose smooth muscle contractile activity figure for rat colon longitudinal muscle bar,
Fig. 7 B are given after TTX blockings for rat colon longitudinal muscle bar, then give the work of variable concentrations fucose smooth muscle contraction
Cardon,
Fig. 7 C are given after L-NAME blockings for rat colon longitudinal muscle bar, then give variable concentrations fucose smooth muscle contraction
Activity diagram,
Fig. 7 D are given after SMT blockings for rat colon longitudinal muscle bar, then give the work of variable concentrations fucose smooth muscle contraction
Cardon,
Fig. 7 E are given after DMSO control incubations for rat colon longitudinal muscle bar, then give variable concentrations fucose smooth muscle receipts
Contracting activity diagram,
Fig. 7 F are given after 7-NI blockings for rat colon longitudinal muscle bar, then give the work of variable concentrations fucose smooth muscle contraction
Cardon.
Specific embodiment
In order to preferably explain the present invention, the main contents of the present invention are further elucidated below in conjunction with specific embodiment, but
Present disclosure is not limited solely to following examples.
Name is write a Chinese character in simplified form
| Write a Chinese character in simplified form | Chinese full name |
| FUC | Fucose |
| FGID | Functional gastrointestinal disorder |
| DSS | Sodium dextran sulfate |
| FL | Fucosyllactose |
| TTX | Fugu ocellatus toxin |
| L-NAME | L-NAME hydrochlorate |
| SMT | S- methyl isothioureas |
| 7-NI | 7- nitro indazoles |
| NOS | Nitricoxide synthase |
| nNOS | Neuron nitric oxide synthase |
| iNOS | Nitric oxide synthase type |
| eNOS | Endothelial nitric oxide synthase |
| DAI | Disease activity index |
Packet is set up and intervened to the DSS of embodiment 1 induction colitis models
1. experimental subject
CD57 male mice body weight 20-22g of 150 6-8 week old, is purchased from CDC of Hubei Province, according to
It is promulgated according to NAS in 2011《Experimental animal feeding and guide for use》, letting animals feed is dynamic in the Central China University of Science and Technology
Thing experimental center SPF level experimental animal room；
2. model packet
Matched group：Simple normal saline gavage, does not process, 10 totally.
Simple fucose intervention group：Give L-fucose gavage merely to process, totally 10.
DSS model group：By DSS induce colitis model standard modeling, normal saline gavage, totally 20.
DSS model fucose intervention groups：Colitis model standard modeling is induced by DSS, the process of L-fucose gavage is given, altogether
20
3. dosage, frequency and approach
Dosage：L-fucose 1mmol/kg, DSS mass fraction 2.5%；
Frequency：DSS adds drinking water freely to drink 7 days, while giving gastric infusion, rests 3 weeks afterwards, then row lower whorl is given
Medicine, amounts to 3 and takes turns
Approach：DSS is oral, L-fucose gavage
Impact of the L-fucose of embodiment 2 to Mouse Weight
1. material：L-fucose purchased and be dissolved in before Sigma-Aldrich, gavage in PBS isotonic buffer solutions
Animal and packet：The CD57 male mices of 6-8 week old, are divided into matched group；
DSS model group；Three groups of DSS model L-fucoses intervention group
2. reagent and instrument：Toy gavage apparatus (Shanghai Medical Apparatus and Instruments Factory, China)
3. method：
1) DSS inducing acutes colitis model：The DAI changes of each group mice and body weight change are recorded daily to 7 days in modeling,
Count and draw DAI scorings and body weight change curve
2) DSS inducing chronics colitis model：The body weight change for recording each group mice daily in modeling is completed to 3 wheels, is counted
And draw body weight change curve
4. result：As shown in figure 1, for chronic DSS induces enteritis group, after recovery the phase shows L-fucose intervention group body weight
Write higher than DSS groups with matched group without significant difference；Colitis model is induced simultaneously for acute DSS, as shown in Fig. 2 L- rock algaes
Sugared intervention group is in DSS groups no matter in body weight, DAI scorings, without significant difference on pathology.This shows that L-fucose can be in digestive tract disease
Become paracmastic and show protective effect, and this effect is produced not due to its direct nutrition to body, but via
Relatively indirectly long-term mode improves the body condition of DSS inductivity enteritis mices, so as to illustrate L-fucose to inflammatory bowel
Disease has therapeutical effect.
Embodiment 3L- fucose is on immune impact
1. material：L-fucose purchased and be dissolved in before Sigma-Aldrich, gavage in PBS isotonic buffer solutions
2. animal and packet：The CD57 male mices of 6-8 week old, are divided into matched group；DSS model group；DSS model fucosees
Three groups of intervention group
3. reagent and instrument：PBS, Percoll separating liquid, platform phenol are blue, anti-CD103, CD11b antibody etc.；Appearance sound refrigerator
BCD-575WYM (Rong Sheng companies, China), Thermo Forma-86 DEG C refrigerators (Thermo companies, the U.S.), low temperature, at a high speed from
Scheming (Eppendorf companies, Germany)
4. method：
(1) vertebra method of breaking puts to death mice, and 75% alcohol-pickled 3min takes whole small intestinal specimen, fully floats in sterilizing PBS solution
Wash.
(2) lamellar of 0.5cm or so is cut into, DTT containing 1mmol/L, 1mmol/L EDTA, 1% antibiotic is inserted
(Penicillin+Streptomycin) and in sterilizing PBS solution 40ml of 5% calf serum, 37 DEG C of incubation 20min, slightly
Vibration, removes epithelial tissue and mucus, repeats this step 2 time.
(3) taking-up tissue is placed in sterilizing PBS and fully rinses, and 1mg/ml collagenases IV are placed in after shredding (can also use glue
Protoenzyme D) in solution 40ml, 37 DEG C of water-baths are incubated 60min.
(4) after successively being filtered with 200 mesh and 400 mesh filter screens, 300 × g is centrifuged 10min；Supernatant is abandoned, with containing 1% antibiotic
(Penicillin+Streptomycin), the full culture medium 4ml suspension cells of the RPMI1640 of 5% calf serum.
(5) 75%percoll solution and each 2ml of 40%percoll solution are configured, and layering is inserted in teat glass,
Its upper strata adds cell suspension, centrifugation (2000rpm, 20min, 20 DEG C) to obtain mononuclearcell, be suspended in containing 5% calf serum
The full culture medium of RPMI1640.
(6) after cell counting, it is centrifuged (300g, 10min), abandons supernatant.With MACS Buffer again suspension cell (80ul
buffer/107Cell), CD11c magnetic bead antibody (20ul/107cell) is added, after fully mixing, 4~8 DEG C of incubation 15min, point
Choosing.With the incubation of CD11b and CD103 fluorescent antibodys, centrifugation, streaming buffer, the detection of streaming instrument are dissolved in.
5. result：As shown in figure 3, the DC hypotype ratios of the regulation and control Treg that mesenteric lymph node is gone back to the nest caused by DSS models
Decline, L-fucose can improve this decline, indicate that L-fucose may have and pass through DC cell regulate and control mesenteric lymph nodes
Treg is activated, and suppresses the potential of colon T h1 and Th17 differentiation.
Impact of the L-fucose of embodiment 4 to intestinal microbial population
1. material：L-fucose is purchased in Sigma-Aldrich
2. animal and packet：The CD57 male mices of 6-8 week old, DSS model group；Two groups of DSS model fucosees intervention group
3. reagent and instrument：PBS, chromatographic grade acetonitrile, methanol, isopropanol, formic acid is purchased from CNW companies；Appearance sound refrigerator BCD-
575WYM (Rong Sheng companies, China), Thermo Forma-86 DEG C refrigerators (Thermo companies, the U.S.), low temperature, high speed centrifuge
(Eppendorf companies, Germany)
4. method：
(1) 50mg samples are taken, homogenate adds 1ml methanol, shakes 30s, are homogenized 2min, ice bath excusing from death 30min,
12000rpm, 4 DEG C centrifugation 10min, take 200 microlitres it is to be measured in sample introduction bottle
(2) chromatographic condition：
Instrument：ACQUITYTM UPLC system chromatographic columns：Waters ACQUITY UPLC HSS T3 posts (2.1mm ×
100mm, 1.8 μm)；Column temperature：40 DEG C of mobile phases：A：Water (V/V) (contains 0.1% formic acid), Mobile phase B：Acetonitrile (contains 0.1% formic acid)
Flow velocity：0.3mL/min sample sizes：4μL
(3) Mass Spectrometry Conditions：ESI sources, scan mode:ESI+, ESI- pattern, capillary voltage:1.4kV and 1.3kV, taper hole
Voltage:40V and 23V, ion source temperature:120 DEG C, desolvation temperature:350 DEG C, taper hole throughput:50L/h, desolventizing air-flow
Amount:600L/h, collision energy (10-40V), ion energy:1V, 1 collection of illustrative plates is gathered per 0.2s；Exact mass is determined and adopts rutin
Solution is lock mass solution.Mass scan range:50-1 500m/z.
5. result：As shown in figure 4, DSS groups pH value is higher than Control groups and fucose intervention group.Intestinal contents pH value
Event closely related with intestinal inner metabolism product combines mass spectrography via liquid matter has carried out preliminary inspection to its metabolite
Survey.Chromatographic results show that fucose group and DSS group metabolites have differences.Mass Spectrometer Method Taurochenodeoxycholic Acid, bilirubin
Fucose intervention group is far above Deng abundance of the material in DSS groups, and the material such as L- excrement gallbladders, D- Urobilins is in fucose group
Abundance is then far above DSS groups.Because bile acid biosynthesis and bilirubin metabolism are in close relations with intestinal flora metabolism in related intestinal,
This experiment thinks that L-fucose may affect body function by regulating intestinal canal flora.
Impact of the L-fucose of embodiment 5 to the Spontaneous Contraction of Isolated colon smooth muscle
1. material：Fucose is purchased in Sigma-Aldrich
2. animal：SD male rats are purchased in CDC of Hubei Province, and row SPF levels are raised
3. reagent and instrument：5600 dew point osmometers；Organ bath's system (Organ Bath)
4. method：
(1) dew point osmometer determines each concentration control sucrose group and fucose experimental group osmotic pressure.
(2) isolated smooth muscle bar experiment detection L-Fucose is to SD male rats near-end and lower distal colon longitudinal muscle, distal end
The impact of the Spontaneous Contraction of colon circular muscle and people's colon longitudinal muscle.
(3) by isolated smooth muscle bar experiment detection L-Fucose in SD male rat lower distal colon stringer muscular spasticities
When (give Ach Chloride 10-5M) to the impact of its Spontaneous Contraction；
5. result：As shown in Fig. 5~6, (1) isolated smooth muscle bar experiment in vitro shows：L-fucose is in 0.25%-
Under 1.5% Concentraton gradient, there is obvious inhibiting effect to the Spontaneous Contraction of rat lower distal colon longitudinal muscle, and as concentration increases
Inhibitory action gradually strengthens (p ＜ 0.05)；And each concentration point is noticeably greater than respective concentration sucrose osmotic pressure matched group,
Inhibitory action Δ AUC% is 27.75 ± 3.22%vs 12.21 ± 0.83% (p ＜ 0.05) during 1.5% concentration；L-fucose is same
Sample can suppress the Spontaneous Contraction of rat proximal colon longitudinal muscle, rat lower distal colon circular muscle and people's colon longitudinal muscle, respectively
Concentration is to rat difference colon muscle strip (lower distal colon longitudinal muscle, proximal colonic longitudinal muscle, lower distal colon circular muscle) inhibitory action
And zero difference (p ＞ 0.05)；
(2) 10 are given after isolated rat lower distal colon longitudinal muscle balance-5M ACH Chloride stimulations treat that its is spontaneously received
After contracting is stable, then L-Fucose is given, with impact nothing of the control sucrose group phase specific concentration at 0.5% to flesh bar Spontaneous Contraction
Difference, can significantly inhibit flesh bar and shrink (p ＜ 0.05) when concentration is in 1% and 1.5% compared with matched group.L- indicated above
Fucose can significantly inhibit the Spontaneous Contraction of rat lower distal colon longitudinal muscle compared with the control of sucrose osmotic pressure, and with concentration
Dependency；And it can also suppress the spontaneity of rat proximal colon longitudinal muscle, lower distal colon circular muscle and people's colon longitudinal muscle
Shrink；When rat lower distal colon longitudinal muscle bar is in spasticity under exogenous Ach effects, L-Fucose can also suppress it certainly
The property sent out contraction movement.
Impact of table 1L- fucosees (control sucrose) to people and rat colon smooth muscle
Note：AUC% Mean ± SEM% represent n=flesh bar numbers.
Impact of the L-fucose to rat lower distal colon longitudinal muscle bar after table 2Ach effects
Note：AUC% Mean ± SEM% represent n=flesh bar numbers
Impact of the L-fucose of embodiment 6 to Isolated colon longitudinal muscle Spontaneous Contraction
1. material：L-fucose is purchased in Sigma-Aldrich
2. animal and packet：SD male rats are purchased in CDC of Hubei Province, and row SPF levels are raised
3. reagent and instrument：Organ bath (Organ Bath)
4. method：By giving isolated smooth muscle bar neuronal sodium channel blocker TTX and various nitric oxide synthetases
(NOS) after inhibitor L-NAME, SMT and 7-NI incubations, then give L-Fucose and observe the change of its action effect.
5. result：As shown in fig. 7, isolated rat colon longitudinal muscle gives 10-5g/L Fugu ocellatus toxin TTX, the total NOS of 10-4M
Inhibitor L-NAME is incubated more than 20min, then gives variable concentrations (0.5%, 1.0%, 1.5%) L-Fucose, with matched group
Compare L-Fucose to significantly reduce (p ＜ 0.05) rejection ability of flesh bar Spontaneous Contraction；And give iNOS inhibitor 10-3M
Weaken the ability (p ＞ 0.05) of L-Fucose suppression flesh bar contractions after SMT incubations compared with matched group；Give 10-5M
Inhibitory action of the L-Fucose to flesh bar Spontaneous Contraction can be also reduced after nNOS inhibitor 7-NI incubations.L- indicated above
It may be enteric nervous (ENS) dependency that Fucose suppresses the effect that flesh bar shrinks, and it may pass through the oxygen of inducing neural type one
Change nitrogen synzyme nNOS synthesis NO to suppress smooth muscle contraction, promote diastole effect.
The impact that 3 two kinds of inhibitor of table are acted on fucose
Note：AUC% Mean ± SEM% represent n=flesh bar numbers
In sum：Jointly explanation L-fucose has remarkable result to embodiment 2~4 to mitigating organism immune response, and
And it has regulating and controlling effect to flora, reduce the unwanted metabolic products such as primary bile acid and generate, its improvement to inflammatory bowel is made
With so as to treat inflammatory bowel；
The inhibitory action that the explanation L-fucose of embodiment 5~6 shrinks to intestinal smooth, illustrates it to function of intestinal canal
Mediation weight loss is the inflammatory bowel of performance and the therapeutical effect of functional gastrointestinal disorder in change, inflammation.
Other unspecified parts are prior art.Although above-described embodiment is made that to the present invention retouching in detail
State, but it is only a part of embodiment of the invention, rather than whole embodiments, people can with according to the present embodiment without
Other embodiment is obtained under the premise of creativeness, these embodiments belong to the scope of the present invention.
Claims (5)
1. a kind of L-fucose is applied in the medicine or health product for the treatment of Alimentary tract disease.
2. application according to claim 1, it is characterised in that：The Alimentary tract disease includes inflammatory bowel, feature stomach
Function of intestinal canal that enteropathy, irritable bowel syndrome and its inflammatory bowel or functional gastrointestinal disorder cause changes, reconcile body weight in inflammation
Decline.
3. a kind of medicine or health-care preparation for treating Alimentary tract disease, it is characterised in that：The pharmaceutical preparation includes L- rock algaes
Sugar.
4. medicine according to claim 3 or health-care preparation, it is characterised in that the medicine or health-care preparation are mouth
Formulation.
5. medicine according to claim 4 or health-care preparation, it is characterised in that the oral formulations are tablet, capsule
Agent or granule.
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| CN109498634A (en) * | 2018-11-23 | 2019-03-22 | 福州大学 | Application of the brown alga oligose in preparation inflammatory enteropathy drug |
| CN113413465A (en) * | 2021-06-15 | 2021-09-21 | 北京大学 | Application of fucosylation inhibitor in resisting inflammation caused by cancer |
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| CN115466297A (en) * | 2022-08-25 | 2022-12-13 | 青岛农业大学 | Application of L-fucose, functional food and animal feed |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109498634A (en) * | 2018-11-23 | 2019-03-22 | 福州大学 | Application of the brown alga oligose in preparation inflammatory enteropathy drug |
| CN113413465A (en) * | 2021-06-15 | 2021-09-21 | 北京大学 | Application of fucosylation inhibitor in resisting inflammation caused by cancer |
| CN113413465B (en) * | 2021-06-15 | 2022-06-03 | 北京大学 | Application of fucosylation inhibitor in resisting inflammation caused by cancer |
| CN115466297A (en) * | 2022-08-25 | 2022-12-13 | 青岛农业大学 | Application of L-fucose, functional food and animal feed |
| CN115381843A (en) * | 2022-10-28 | 2022-11-25 | 四川大学华西医院 | Application of L-fucose in preparing medicine for treating respiratory system diseases |
| CN115381843B (en) * | 2022-10-28 | 2023-01-10 | 四川大学华西医院 | Application of L-fucose in preparing medicine for treating respiratory system diseases |
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Application publication date: 20170517 |