CN108478586A - The pharmaceutic usage of neohesperidin - Google Patents
The pharmaceutic usage of neohesperidin Download PDFInfo
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- CN108478586A CN108478586A CN201810134639.7A CN201810134639A CN108478586A CN 108478586 A CN108478586 A CN 108478586A CN 201810134639 A CN201810134639 A CN 201810134639A CN 108478586 A CN108478586 A CN 108478586A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The present invention discloses a kind of pharmaceutic usage of neohesperidin, specially, purposes of the neohesperidin in preparing treatment or alleviating the drug of bronchial asthma, either prepare eliminate or alleviate caused by bronchial asthma appetite reduce product in purposes or prepare treatment due to Th1/Th2 cellular immunities it is unbalance caused by relevant disease drug in purposes；The invention provides new approach for its application.
Description
Technical field
The invention belongs to field of medicaments, are related to the pharmaceutic usage of neohesperidin, and in particular to neohesperidin is being made
Purposes in the standby drug treated or alleviate bronchial asthma.
Background technology
Neohesperidin is a kind of flavanone glycoside compound, is Rutaceae citrus plant secondary metabolite, extensively
It is distributed in various plants.Research shows that neohesperidin is promoting the sides such as WeiDongLi Capsule, reducing blood lipid, hypoglycemic, promotion skin microcirculation
Face has stronger bioactivity.China Patent No.：1836665 B of CN disclose entitled " neohesperidin or combinations thereof
The patent of invention of the pharmaceutical applications of object " provides neohesperidin or combinations thereof object and is preparing the purposes for promoting WeiDongLi Capsule drug.In
State's patent No.：1317938 A of CN disclose entitled " related to blood fat and blood glucose level raising for treating or preventing
Disease the composition containing the double hydrogen chalcones of neohesperidin " patent of invention, the composition includes a effective amount of new orange peel
Glycosides double hydrogen chalcone and pharmaceutically acceptable excipient, carrier or diluents.China Patent No.：102258528 A of CN are disclosed
The patent of invention of entitled " new application of neohesperidin ", it was demonstrated that neohesperidin or the plant extracts comprising neohesperidin
It is preparing for improving and/or promoting skin microcirculation, or elimination and/or alleviation and the bad related illness of skin microcirculation
Or the purposes in the product of state.China Patent No.：103142631 A of CN disclose a kind of entitled " Chinese medicine composition
The patent of invention of application as antidepressant " discloses the composition of neohesperidin and aurantiamarin in antidepressant
Application.However, yet there are no new application of the neohesperidin in preparing treatment or alleviating the drug of bronchial asthma.
Invention content
The purpose of the present invention is to provide the pharmaceutic usage of neohesperidin, specifically, neohesperidin prepare treatment or
Alleviate the purposes in the drug of bronchial asthma, or the appetite reduction caused by bronchial asthma is eliminated or alleviate preparing
Product in purposes, or prepare treatment due to Th1/Th2 cellular immunities it is unbalance caused by relevant disease drug in
Purposes.
The present invention is found surprisingly that in the mouse asthmatic model that OVA is induced, and injects neohesperidin solution（It is a concentration of
25mg/kg or 50mg/kg）, the food-intake of mouse starts in rising trend after the 22nd day, it was demonstrated that the use of neohesperidin can delay
Solve the influence generated to mice with asthma appetite after OVA inductions.
In addition, injecting neohesperidin solution by the mice with asthma induced to OVA（A concentration of 25mg/kg or
50mg/kg）, the content of Th1 cell factors IFN-γ in Mice Body can be increased, Th2 cell factors IL-5 in Mice Body is reduced
The content of concentration and IL-4, adjusting Th1/Th2 cellular immunities are unbalance, to inhibit the generation of asthma, have and alleviate or treat
The effect of bronchial asthma.
The advantages of the present invention：The present invention demonstrates neohesperidin by experiment has treatment or alleviation branch gas
The effect of pipe asthma, while can also eliminate or alleviate due to symptoms such as anorexias caused by bronchial asthma, which is
Its application provides new approach, and small toxicity, no conventional anti-bronchus side effects of pharmaceutical drugs.
Description of the drawings
Fig. 1 is the food-intake variation diagram during each group mouse experiment；
Fig. 2 is the changes of weight figure during each group mouse experiment；
Fig. 3 is the mass change figure of each group mouse thymus and spleen；
Fig. 4 be each group mouse bronchoalveolar lavage fluid in IL-4 contain spirogram；
Fig. 5 be each group mouse bronchoalveolar lavage fluid in IL-5 contain spirogram；
Fig. 6 be each group mouse bronchoalveolar lavage fluid in IFN-γ contain spirogram；
Fig. 7 be T lymphocyte CDs 4, CD8 contain spirogram；
Fig. 8 is that neohesperidin dyes pathological change figure to asthmatic mouse HE；
Wherein, in Fig. 8, A is the HE dyeing of naive mice lung tissue；B is the HE dyeing of model group mouse lung tissue；C is low concentration
The HE dyeing of administration group mouse lung tissue；D is the HE dyeing of high concentration administration group mouse lung tissue；E is Dexamethasone group mouse lung group
Knit HE dyeing.
Specific implementation mode
To make the clear technical scheme of the present invention of those skilled in the art and its advantage, with reference to zoopery pair
The present invention is further described, but is not intended to limit the scope of protection of the present invention.
1, materials and methods
1.1 experimental animal
BALB/c mouse, female, weight 20-25g select healthy mice 50, are divided into 5 groups with randomized blocks, every group 10,
If blank control group, model control group, positive drug control group（Dexamethasone sodium phosphate injection, a concentration of 0.25mg/mL）,
Low concentration administration group（Neohesperidin solution, a concentration of 25mg/mL）, high concentration administration group（Neohesperidin solution, it is a concentration of
50mg/mL）.
1.2 sample treatment
By Mouse feeder one week, after adapting it to growing environment, start to test.This experiment is all noted using hypodermic injection and abdominal cavity
The mode being combined is penetrated to be injected.
1.3 solution are prepared
（1）OVA induces liquid：9.0 mg OVA are weighed, 18mL physiological saline is dissolved in, the hydrogen-oxygen of equivalent is then added into the solution
Change aluminium adjuvant, so that it is fully dissolved, matching while using.
（2）OVA exciting liquids：8.0 mg OVA are weighed, are placed in small test tube, adds 4mL physiological saline, it is made fully to dissolve,
Matching while using.
（3）Neohesperidin solution：The neohesperidin that sample purity is 95% is dissolved in physiological saline, makes its concentration be respectively
25mg/mL and 50mg/mL.
（4）Dexamethasone sodium phosphate injection：Take dexamethasone sodium phosphate injection（5mg/mL）1mL uses physiological saline
It is diluted to 20mL, a concentration of 0.25mg/mL of dexamethasone sodium phosphate.
1.4 Induction Process
（1）Blank control group：Each every injecting normal saline, NaCl contents 0.9% at the 0th, 7,14 day.
（2）Model control group：At the 0th, 7,14 day, every injection 0.2mL OVA induced liquid every time.
（3）Positive drug control group：At the 0th, 7,14 day, every injection 0.2mL OVA induced liquid every time.
（4）Low concentration administration group：At the 0th, 7,14 day, every injection 0.2mL OVA induced liquid every time.
（5）High concentration administration group：At the 0th, 7,14 day, every injection 0.2mL OVA induced liquid every time.
1.5 excitation process
（1）Blank control group：At the 21st, 22,23 day, 0.2mL physiological saline is injected intraperitoneally, after 1h is administered, with 50uL physiology salts
Water excites mouse collunarium.
（2）Model control group：At the 21st, 22,23 day, 0.2mL physiological saline is injected intraperitoneally, after 1h is administered, uses 50uLOVA
Exciting liquid collunarium excites.
（3）Positive drug control group：At the 21st, 22,23 day, 0.2mL dexamethasone solutions are injected intraperitoneally, after 1h is administered,
It is excited with 50uLOVA exciting liquid collunariums.
（4）Low concentration administration group：At the 21st, 22,23 day, 0.2mL low concentration neohesperidins are injected intraperitoneally, after 1h is administered,
It is excited with 50uLOVA exciting liquid collunariums.
（5）High concentration administration group：At the 21st, 22,23 day, 0.2mL high concentration neohesperidins are injected intraperitoneally, after 1h is administered,
It is excited with 50uLOVA exciting liquid collunariums.
The collection of 1.6 lung tissues
After the 24th day eyeball takes blood to put to death mouse, mouse lung tissue is taken, is cleaned up with physiological saline, then with 10% formaldehyde
It is fixed, 4 DEG C of preservations.
The collection of 1.7 bronchoalveolar lavage fluids
After the 24th day eyeball takes blood to put to death mouse, each group takes 7 mouse to carry out alveolar wass experiment；With PBS, lavation is small three times
Mouse lungs obtain bronchoalveolar lavage fluid, 4 DEG C of centrifugations（500 rpm, 5min）, take supernatant.
The preparation of 1.8 T cells
Eyeball takes the mouse after blood, takes out spleen and thymus gland, takes spleen cell, purify to obtain T cell using nylon cant method.
The measurement of IL-4, IL-5 in 1.9 bronchoalveolar lavage fluids, IFN-γ
It is detected according to the ELISA kit specification of IL-4, IL-5 of bronchoalveolar lavage fluid, IFN-γ.
The measurement of CD4 and cd8 cell quantity in 1.10 T lymphocytes
500 μ lPBS of obtained T lymphocytes are resuspended, required antibody is separately added into.Refrigeration is incubated half an hour, and 4 DEG C centrifuge,
It is primary that cell is cleaned with 1mLPBS, is finally resuspended in 300 μ LPBS, upper machine testing.
1.11 dye asthmatic mouse HE with reference to existing HE staining methods.
2, experimental result
The front and back food-intake variation of 2.1 each group mouse induction, the result is shown in Figure 1.
It will be seen from figure 1 that the food-intake of each group mouse reached most at the 21st day in addition to blank group and high concentration medicine group
High level；The food-intake of naive mice persistently increases, and reaches maximum value at the 23rd day.It is each in addition to blank group after collunarium excitation
Group mouse food-intake significantly reduces, it is possible thereby to which each group mouse will produce asthma symptoms after illustrating OVA inductions, to food-intake
It has an impact.Compared with model group, low concentration administration group（25mg/kg）With high concentration administration group（50mg/kg）The feed of mouse
Amount starts in rising trend after the 22nd day；Compared with positive drug control group, the food-intake self-induction of Dexamethasone group mouse
It persistently reduces afterwards, it can be seen that this positive drug of dexamethasone has an impact mouse appetite, and the use of neohesperidin can delay
Solve the influence generated to mice with asthma appetite after OVA inductions.
The front and back changes of weight of 2.2 each group mouse induction, is as a result shown in Fig. 2.
As shown in Fig. 2, in addition to high concentration medicine group and blank group, each group mouse weight reached maximum value at the 21st day；
The continued weight of naive mice increases, and weight reached maximum value at the 23rd day.After collunarium excitation, each group in addition to blank group
Mouse weight reduces.It can be seen that after collunarium excitation, the weight of mouse changes, and OVA asthmatic models is prompted to be created as
Work(.
The thymus gland of 2.3 each group mouse and the quality of spleen, are as a result shown in Fig. 3.
Thymus gland is the important lymphoid organ of body, is T cell differentiation, development, ripe place.As shown in figure 3, through statistics
Credit is analysed, and there are pole significant differences compared with model group mouse thymus quality for naive mice thymic factor D injection（p<0.01）, show
The thymus gland of each group mouse is had an impact after OVA inductions.
Spleen is the maximum immune organ of body, be lymphocyte transmigration and receiving occur after antigenic stimulus immune response,
Generate the important place of immune effector molecule.As shown in figure 3, through statistical analysis, naive mice spleen weight and model group
Mouse spleen quality is compared to there are pole significant differences（p<0.01）, show that the spleen of each group mouse after OVA is induced changes；It is low
There are pole significant differences compared with model group mouse spleen quality for acute drug group mouse spleen quality（p<0.01）, show new orange
Skin glycosides can reduce its influence to immune system, to inhibit the generation of asthma.
The content of IL-4 in 2.4 each group mouse bronchoalveolar lavage fluids, is as a result shown in Fig. 4.
IL-4 and IL-5 is a kind of cell factor secreted by Th2 cells, can activate mast cell, promote growth
Differentiation, forms the speed hair phase reaction of asthma, while the various inflammatory cells of air flue being activated to start asthma late phase reaction.It can by Fig. 4
Know, compared with blank group, the content of the IL-4 in model group mouse bronchoalveolar lavage fluid significantly increases；It is low dense compared with model group
Spend medicine group（25mg/kg）The content of IL-4 in mouse bronchoalveolar lavage fluid reduces.It follows that neohesperidin（25mg/kg）
It is inhibited to asthma.
The content of IL-5 in 2.5 each group mouse bronchoalveolar lavage fluids, is as a result shown in Fig. 5.
As shown in Figure 5, there are pole significance differences compared with model group for the content of the IL-5 in naive mice bronchoalveolar lavage fluid
It is different（p<0.01）, show the Th2 cell factors raising of each group mouse after OVA inductions；Compared with model group, low concentration medicine group
（25mg/kg）With high concentration medicine group（50mg/kg）The content of IL-5 in mouse bronchoalveolar lavage fluid significantly reduces.Thus table
Bright, neohesperidin can be lost by the concentration of Th2 cell factors IL-5 in reduction Mice Body to adjust Th1/Th2 cellular immunities
Weighing apparatus, inhibits the generation of asthma.
The content of IFN-γ, is as a result shown in Fig. 6 in 2.6 each group mouse bronchoalveolar lavage fluids.
IFN-γ is I type T helper cell（Th1 cells）Significant cell factor.It will be appreciated from fig. 6 that naive mice
The content of IFN-γ is higher compared with model group in bronchoalveolar lavage fluid；Compared with model group, low concentration medicine group（25mg/kg）With
High concentration medicine group（50mg/kg）The content of IFN-γ increases in mouse bronchoalveolar lavage fluid.It follows that neohesperidin can pass through
The content of Th1 cell factor IFN-γ in Mice Body is increased, it is unbalance to adjust Th1/Th2 cellular immunities, inhibit the hair of asthma
It is raw.
The T lymphocyte CDs 4 of 2.7 each group mouse, the content of CD8, are as a result shown in Fig. 7.
Cd4 cell is also referred to as T helper lymphocytes, and when anaphylactogen is invaded, CD4 sends out confrontation information to immune system,
The pivotal role of immune response is played, and cd4 cell number percent can increase at this time.As shown in Figure 7, compared with blank group,
The cd4 cell number percent of model group increases.It follows that the T lymphocytes of mouse are influenced after OVA inductions；With mould
Type group is compared, and the cd4 cell number percent of low concentration medicine group and high concentration medicine group reduces, and high concentration medicine group
Cd4 cell number percent closest to the ratio normally organized.
It is to inhibit and resist anaphylactogen after being connected to confrontation information that cd8 cell, which is also known as T to inhibit lymphocyte, effect,.When
After anaphylactogen invasion, the number percent of cd8 cell can reduce.As shown in Figure 7, compared with blank group, the cd8 cell of model group
Number percent reduces；Compared with model group, the cd8 cell number percent of low concentration medicine group and high concentration medicine group increases
Add, and the closest ratio normally organized of cd8 cell number percent of high concentration medicine group.It follows that neohesperidin has
Play the role of inhibiting asthma.
2.8 neohesperidins dye asthmatic mouse HE the influence of pathological change, as a result see Fig. 8.
As shown in figure 8, naive mice lung tissue section has no or accidental extremely slight pathology damage, peripheral vessels and branch
Tracheae contains minute quantity inflammatory cell, and alveolar structure is complete.Compared with blank group, the bronchus of model group mouse lung tissue slice
And massive inflammatory cells infiltrated around blood vessel, a large amount of eosinophil exudations, peripheral tissue edema are serious.With model group phase
Than the mouse lung inflammation of low concentration medicine group and high concentration medicine group has different degrees of improvement, bronchus and blood vessel week
Enclose and tube chamber in visible mild to moderate inflammatory cell infiltration, eosinophils situation mitigates, alveolar and bronchiole
Edematous condition is alleviated.It follows that neohesperidin can reduce the infiltration of inflammatory cell and eosinophil in lung tissue
Situation, to inhibited to bronchial asthma.
Claims (1)
1. neohesperidin prepare treatment or alleviate bronchial asthma drug in purposes, or prepare eliminate or alleviate by
Purposes in the product that the appetite caused by bronchial asthma reduces, or treatment is being prepared since Th1/Th2 cellular immunities are lost
Purposes in the drug of relevant disease caused by weighing apparatus.
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| CN201810134639.7A CN108478586A (en) | 2018-02-09 | 2018-02-09 | The pharmaceutic usage of neohesperidin |
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| CN201810134639.7A CN108478586A (en) | 2018-02-09 | 2018-02-09 | The pharmaceutic usage of neohesperidin |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102935131A (en) * | 2011-08-15 | 2013-02-20 | 天津药物研究院 | Application of Fructus Aurantii Immaturus total flavonoid extract in preparation of drug treating bronchial asthma |
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2018
- 2018-02-09 CN CN201810134639.7A patent/CN108478586A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102935131A (en) * | 2011-08-15 | 2013-02-20 | 天津药物研究院 | Application of Fructus Aurantii Immaturus total flavonoid extract in preparation of drug treating bronchial asthma |
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Application publication date: 20180904 |
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