CN106491585A - Application of the rotenone in fat and Fatty Liver Disease medicine is prepared - Google Patents
Application of the rotenone in fat and Fatty Liver Disease medicine is prepared Download PDFInfo
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- CN106491585A CN106491585A CN201710010633.4A CN201710010633A CN106491585A CN 106491585 A CN106491585 A CN 106491585A CN 201710010633 A CN201710010633 A CN 201710010633A CN 106491585 A CN106491585 A CN 106491585A
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- fat
- rotenone
- fatty liver
- mouse
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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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
Abstract
The present invention relates to a kind of new opplication of application of the rotenone in medicine is prepared, specifically rotenone in fat and Fatty Liver Disease medicine is prepared.The present invention feeds high fat high cholesterol diet induction obesity and fatty liver mouse model in ApoE deficient mices, after low dose of (100ppm) rotenone treatment of application, it was found that Mouse Weight is significantly mitigated, internal subcutaneous fat, perirenal fat, gonadal fat and liver fat are substantially reduced, and show that rotenone is a kind of effective means for treating fatty liver and obesity, prepare fatty liver and fat disease medicament provides possibility so as to be that later stage research and development are related.
Description
Technical field
The present invention relates to application of the rotenone in medicine is prepared, specifically rotenone are preparing fat and fatty liver disease
A kind of new opplication in medicine, belongs to biomedicine technical field.
Background technology
As the fast development of social economy, the living standard of compatriots are increased substantially, life style also there occurs huge
Change, corresponding is that the incidence of metabolic disease increases significantly, this not only had a strong impact on the life-span of patient and
Quality of life, also brings great financial burden to country and patient home.Effectively preventing and treating metabolic disease has become China
Or even a global difficult problem.Obesity is a kind of chronic metabolic disease caused by many factors, shows as fat cell
Volume and cell number increase and cause the percentage of body fat percentage of liveweight to increase extremely, and in the excessive deposition fat in local.Fat
Liver is the excessive pathology of fat accumulation in the liver cell caused due to many reasons.Fatty liver disease is just seriously threatening being good for for compatriots
Health, becomes the second largest hepatopathy for being only second to virus hepatitis.The degree of fatty liver is directly proportional to body weight, 30%~50% obesity
Merge fatty liver, severe obesity fatty liver variability up to 61%~94%.Therefore, exploitation novel therapeutic is fat and fatty
Liver medicine is still the key for the treatment of metabolic disease.
Rotenone (also known as malicious trifoliate jewelvine, English name tubatoxin), be present in the seed of pulse family trifoliate jewelvine platymiscium, stem and
Root, water insoluble, it is dissolved in alcohol, acetone, chloroform, carbon tetrachloride, ether etc..Agricultural insecticide is mainly used as, people can be also prevented and treated
Carcass epizoa and Biochemical Research.Controlling object has:Aphid, plant hopper, striped flea-beetle, thrips, aulacophora femoralis, daikon leaf beetle, dark greyish green
Worm, prodenia litura, beet armyworm, diamondback moth etc..It is a kind of very strong material of specificity in toxicology, to insect especially dish
White butterfly larva, diamondback moth and aphid have strong tagging and two kinds of effects of stomach toxicity.The research of early stage shows that rotenone is mainly
A certain composition between nadh dehydrogenase and ubiquinone is had an effect, and is suppressed the electron transport chain of pest cell, so as to
Reducing biological internal ATP levels finally makes insect cannot get energy supply, then drumble, paralysis and slow dead.
At present, there is no is used for any report for treating obesity and fatty liver with regard to rotenone.
Content of the invention
In order to overcome the deficiencies in the prior art, present invention aim at providing rotenone is preparing fat and fatty liver disease
A kind of application in medicine, there is provided new treatment drug candidate.Supplement the deficiency of existing medicine.
The technical solution used in the present invention is as follows:
Application of the rotenone in fat and Fatty Liver Disease medicine is prepared.
Further, the dosage of the rotenone is low dosage.
Further, the dosage of the rotenone is 100ppm.
Present invention rotenone used in the mouse high fat diet animal model, its are that a kind of specific mitochondrial is combined
- 1 inhibitor of body, with very strong fat-soluble, directly can enter kytoplasm by cell membrane, specifically suppress mitochondrial respiratory
Chain cpd I, so as to reduce the level of biological ATP in vivo, reduces the supply of energy, mitigates formation and the lipid of fat cell
Transhipment, and then mitigate formation and the progress of fat and fatty liver.
The technique effect of the present invention:
1st, the present invention feeds high fat high cholesterol diet induction obesity and fatty liver mouse model in ApoE deficient mices,
After low dose of (100ppm) rotenone treatment of application, it is found that Mouse Weight is significantly mitigated, internal subcutaneous fat, all fat of kidney
Fat, gonadal fat and liver fat are substantially reduced, and show that rotenone is a kind of to treat the effective of fatty liver and obesity
Means, prepare fatty liver and fat disease medicament provides possibility so as to be that later stage research and development are related.
2nd, rotenone is a kind of mitochondria activity inhibitor, the result of study prompting, suppresses mitochondria activity by appropriate,
So as to reduce the level of biological ATP in vivo, the supply of energy is reduced, with certain potential applicability in clinical practice.
3rd, rotenone, is mainly used as agricultural insecticide at present, has strong toxic action, the rotenone of high dose to insect
For cell and living individual have toxic and side effect, what therefore we selected is a comparatively safe low dosage
(100ppm).
Description of the drawings
Fig. 1:Mouse Weight change curve is fed in control group/rotenone administration group 0~8 week;
Fig. 2:Control group/rotenone administration group feeds the ratio of mouse subcutaneous fat percentage of liveweight;
Fig. 3:Control group/rotenone administration group feeds the ratio of mouse perirenal fat percentage of liveweight;
Fig. 4:Control group/rotenone administration group feeds the ratio of mouse propagation gland fat percentage of liveweight;
Fig. 5:Under oil red O stain, control group/rotenone administration group feeds mouse fatty liver degree (mirror figure below);
Fig. 6:Lower control group/rotenone the administration group of HE dyeing feeds mouse fatty liver degree (mirror figure below);
Fig. 7:Control group/rotenone administration group feeds the ratio of total triglyceride in mouse liver.
Specific embodiment
Technical scheme is described in further detail below with reference to specific embodiments and the drawings.
Rotenone used in following examples of the present invention is purchased in Sigma;ApoE knock-out mices are purchased in Peking University
Medical board Experimental Animal Center.
1 rotenone of embodiment can reduce high fat diet Mouse Weight
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Mouse Weight is detected in experimentation, such as Fig. 1 institutes
Show the body weight of rotenone treatment group mouse from feed one week when be less than control group, with significant difference.
2 rotenone of embodiment can reduce high fat diet mouse subcutaneous fat than row
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Experiment takes mouse subcutaneous fat after terminating, and weighs,
The ratio of subcutaneous fat percentage of liveweight, statistics control group and rotenone treatment group is calculated, such as Fig. 2 results show that rotenone can drop
Low high fat diet mouse subcutaneous fat ratio row, with statistics difference (p<0.0001).
3 rotenone of embodiment can reduce high fat diet Mouse Kidney week fat ratio row
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Experiment takes mouse perirenal fat after terminating, and weighs,
The ratio of perirenal fat percentage of liveweight, statistics control group and rotenone treatment group is calculated, such as Fig. 3 results show that rotenone can drop
Low high fat diet Mouse Kidney week fat ratio row, with statistics difference (p=0.0006).
4 rotenone of embodiment can reduce high fat diet mouse propagation gland fat ratio row
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Experiment takes mouse propagation gland fat after terminating, claim
Weight, calculates the ratio of gonadal fat percentage of liveweight, statistics control group and rotenone treatment group, and such as Fig. 4 results show rotenone
High fat diet mouse propagation gland fat ratio row can be reduced, with statistics difference (p<0.0001).
5 rotenone of embodiment can reduce high fat diet mouse fatty liver degree
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Experiment takes mouse liver after terminating, frost is embedded,
Section, oil red O stain, the fat drips in liver can dye redness, and such as Fig. 5 results show that rotenone can reduce fat in mouse liver
The accumulation of fat.
6 rotenone of embodiment can reduce high fat diet mouse fatty liver degree
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Experiment takes mouse liver, mouse liver after terminating
After paraformaldehyde is fixed, dehydration, FFPE, section, then HE dyeing, the fat drips in liver can be shown as cavity., such as
Fig. 6 results show that rotenone can reduce the accumulation of fat in mouse liver.
7 rotenone of embodiment can reduce total triglyceride in high fat diet mouse liver
The ApoE deficient mices that high fat high cholesterol diet is fed are divided into control group and rotenone treatment group, 7 per group,
Add the rotenone of 100ppm, continuous nursing 8 weeks in treatment group's mouse feed.Experiment takes mouse liver after terminating, using reagent
Box extracts the total triglyceride in mouse liver, measures concentration, calculates the content of total triglyceride in mouse liver.Such as Fig. 7
As a result show that rotenone can reduce the content of total triglyceride in high fat diet mouse liver.
Claims (3)
1. application of the rotenone in fat and Fatty Liver Disease medicine is prepared.
2. application of the rotenone described in claim 1 in fat and fatty liver medicament is prepared, it is characterised in that the fish
The dosage of rattan ketone is low dosage.
3. application of the rotenone described in claim 2 in fat and fatty liver medicament is prepared, it is characterised in that the fish
The dosage of rattan ketone is 100ppm.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114651785A (en) * | 2022-03-28 | 2022-06-24 | 中山大学 | Non-alcoholic steatohepatitis mouse model construction method based on PEDF/ApoE double gene knockout and application |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150051429A (en) * | 2013-11-04 | 2015-05-13 | 아주대학교산학협력단 | Composition for preventing or treating obesity comprising Rotenone |
US20150225416A1 (en) * | 2012-10-24 | 2015-08-13 | Korea Atomic Energy Research Institute | Novel Rotenone Derivatives and a Use Thereof |
CN104983727A (en) * | 2015-07-23 | 2015-10-21 | 上海市第六人民医院 | Application of rotenone in preparation of drugs for reducing liver fat deposition |
-
2017
- 2017-01-06 CN CN201710010633.4A patent/CN106491585A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150225416A1 (en) * | 2012-10-24 | 2015-08-13 | Korea Atomic Energy Research Institute | Novel Rotenone Derivatives and a Use Thereof |
KR20150051429A (en) * | 2013-11-04 | 2015-05-13 | 아주대학교산학협력단 | Composition for preventing or treating obesity comprising Rotenone |
CN104983727A (en) * | 2015-07-23 | 2015-10-21 | 上海市第六人民医院 | Application of rotenone in preparation of drugs for reducing liver fat deposition |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114651785A (en) * | 2022-03-28 | 2022-06-24 | 中山大学 | Non-alcoholic steatohepatitis mouse model construction method based on PEDF/ApoE double gene knockout and application |
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Application publication date: 20170315 |