CN102552238A - New application of luteolin - Google Patents
New application of luteolin Download PDFInfo
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- CN102552238A CN102552238A CN2011104308732A CN201110430873A CN102552238A CN 102552238 A CN102552238 A CN 102552238A CN 2011104308732 A CN2011104308732 A CN 2011104308732A CN 201110430873 A CN201110430873 A CN 201110430873A CN 102552238 A CN102552238 A CN 102552238A
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Abstract
The invention discloses new application of luteolin, namely application of the luteolin to preparation of medicines for treating fatty liver. Animal experiments indicate that the luteolin can reduce the content of cholesterol and triglyceride in blood and the synthesis of the triglyceride in liver to block the source of lipid accumulation in the liver, so the luteolin is widely applied to preparing the medicines for treating the fatty liver, is high in practicability and has good economic benefit and social effect.
Description
Technical field
The present invention relates to luteolin, be specifically related to a kind of new purposes of luteolin.
Background technology
Fatty liver has become the fastest chronic disease of China's sickness rate rising at present.The ratio of finding fatty liver in recent years rises year by year, and sickness rate is 5% among the crowd, and also has the trend of rejuvenation.The expert points out that 40% above obese people suffers from fatty liver, and overnutrition, excessive drinking, diabetes are the principal elements of causing a disease, and other diseases also can cause fatty liver, such as tuberculosis, serious anemia, pulmonary heart disease etc.; In addition, some drugs or poisonous substance also can cause fatty liver.The harm of fatty liver is a lot, mainly comprises: (1) forms hepatic fibrosis, liver cirrhosis.Fat drips and increases in the hepatocyte, makes hepatic cell fattydegeneration, and secular hepatocellular degeneration meeting causes liver cell regeneration obstacle and necrosis, and then forms hepatic fibrosis, liver cirrhosis.(2) bring out or increase the weight of hypertension, coronary heart disease, atherosclerosis.The disease progression research of fatty liver shows that the many complicated hypertensions of alcohol fatty hepatopath, coronary heart disease cause myocardial infarction easily.(3) encephalopathy fatty liver syndrome.Some overweight peoples that fatty liver takes place usually show as pernicious obesity, the very easily concurrent mortality cardiovascular and cerebrovascular disease of this type patient.(4) bring out or increase the weight of diabetes.According to investigations, merge the about 50% of fatty liver in the diabetics, complication with diabetes is 30%～40% in the Patients with Fatty Liver.(5) bring out hepatocarcinoma.Though the generation of fatty liver and primary hepatocarcinoma does not have direct relation, but the cause of disease of fatty liver, as drink, malnutrition, drug effect and noxious substance infringement etc., can bring out hepatocarcinoma.Therefore, fatty liver also can increase the incidence probability of hepatocarcinoma.
Fatty liver belongs to the liver metabolism obstacle disease, thus be reversible, through rationally recovering normal fully after the treatment.Except that diet, exercise therapy, make to heal with medicine, main medicine comprises: (1) type of protecting the liver medicine more at present.Liver protecting therapy is the indispensable treatment measure of most of Patients with Fatty Liver, once making a definite diagnosis fatty liver, in etiological treatment and dietetic therapy, all should be aided with hepatic, is beneficial to the recovery as early as possible of liver function.Hepatoprotective commonly used has: glucuronolatone, vitamin C, inosine etc.(2) blood fat reducing class medicine.Patients with Fatty Liver is because of lipodystrophy, and triglyceride and cholesterol all have rising in various degree in the body, and often with hyperlipemia.So need fat-reducing medicament inevitably, like Max EPA, Herb Gynostemmae Pentaphylli general glycoside, JIANGZHILING, inositol niacinate and methionine etc.Also can obey some fat Chinese herbal medicine of dispelling.(3) other ancillary drug.Patients with Fatty Liver is often with vitamin deficiency, so also should take vitamin C, vitamin B12, folic acid etc., vitamin C can promote decomposition, the conversion of cholesterol, can strengthen the effect that liver is removed cholesterol.Riboflavin, pyridoxic acid(0) etc. also have delipidation.When the patient with the digestive tract malaise symptoms as feeling sick, when inappetence, abdominal distention, constipation or loose stool, can giving symptomatic treatment, corresponding symptomatic drugs such as oral yeast tablet.
At present, clinical blood fat reducing class drug main commonly used will comprise: (1) Statins.Trimethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor; Be cholesterol biosynthesis enzyme inhibitor (statins); Be the synthetic rate-limiting enzyme of cell inner cholesterol, i.e. the inhibitor of HMG-CoA reductase is most widely used clinically one type of lipid-regulation medicine at present.Because the English name of this type medicine all contains " statin ", so often abbreviate Statins as.In recent years, the statins serious toxic and side effects that often come to light.Sensational " visiing sthene " incident once took place in calendar year 2001.China National Drug Administration and August 9 calendar year 2001 are sent emergency notice, ban use of cerivastatin sodium (visiing sthene).It is reported that since the statins listing, the whole world only has 6,000,000 humans to cross it; And visit sthene as one of statins, cause more than 30 American to lose one's life because of toxic and side effects is excessive.The a recent period of time, external medium are reported one after another: statins has also brought toxic and side effects such as liver function decline, myalgia in blood fat reducing.(2) shellfish is special type.The principal indication of fibrate is: hypertriglyceridemia or be master's combined hyperlipidemia familial with the triglyceride rising.The fibrate of clinical practice at present mainly contains ciprofibrate, bezafibrate, fenofibrate and gemfibrozil.According to clinical practice, these medicines are triglyceride reducing 22%～43% effectively, is merely 6%～15% and reduce TC, and the effect of high density lipoprotein increasing is in various degree arranged.The untoward reaction of this medicine is gastrointestinal reaction, feels sick, suffers from diarrhoea, and has the report life-time service can cause hepatic injury.(3) nicotinic acid class.Nicotinic acid class medicine belongs to vitamin B group, when consumption surpasses it as the dosage of vitamin effect, tangible effect for reducing fat can be arranged.The scope of application of such medicine is wider, can be used for removing the subtype familial hypercholesterolemia that isozygotys, and any kind hyperlipemia beyond the I type hyperlipoproteinemia.But the quick releasing formulation erious adverse reaction of this medicine is not generally used separately.(4) cholic acid chelating agent.This type medicine is also referred to as cholic acid at a distance from putting agent.Colestyramine (Cholestyramine) is arranged, and common drug has cholestipol.The common untoward reaction of this medicine is gastrointestinal reaction, feel sick, constipation or diarrhoea, intestinal obstruction or headache etc.(5) cholesterol absorption inhibitor.This type of drug main will reach the purpose of blood fat reducing through suppressing the absorption of interior diet of intestinal and bile cholesterol.At present, such medicine listing seldom.
Luteolin (luteolin) is a kind of natural flavone compounds, is present in the various plants.Have multiple pharmacologically active, like antiinflammatory, antiallergic, antitumor, antibiotic, antiviral etc., clinically be mainly used in cough-relieving, eliminate the phlegm, antiinflammatory, treatment cardiovascular disease, treatment " amyotrophic lateral sclerosis ", SARS, hepatitis etc.But in treatment fatty liver disease, have no research and report.
Summary of the invention
Goal of the invention: to the deficiency that exists in the prior art, the purpose of this invention is to provide a kind of new purposes of luteolin, to realize that it is widely used in preparation treatment fatty liver medicine.
Technical scheme: in order to realize the foregoing invention purpose, the technical scheme that the present invention adopts is following:
A kind of new purposes of luteolin is for being used for treating the application of fatty liver medicine in preparation.
A kind of medicine that is used to treat fatty liver, effective ingredient are luteolin.
Luteolin, chemical name: 3', 4', 5,7-luteolin, another name: cyanidenon, cyanidenon, CasNo:491-70-3, chemical formula: C
15H
10O
6, molecular weight: 286.23.Physical behavior: yellow acicular crystal, fusing point 328-330 ℃.Be slightly soluble in water, the tool faintly acid dissolves in the alkaline solution, and is stable under the normal condition.The many forms with glucosides of luteolin are present in the various plants, and these plants are higher with Herba Dracocephali Integrifolii, Fructus Capsici, Flos Chrysanthemi Indici, Flos Lonicerae, Folium Perillae content, have antitussive and phlegm-dispelling functions.Research shows that luteolin suppresses the macrophage phosphorylation, suppresses the activity of transcription factor NF-kB, can suppress the inductive macrophage of lipopolysaccharide (LPS) and produce cytokine IL-6, TNF-a.Luteolin can also improve IFN-γ, reduces specificity Ig-E, reduces eosinophilic granulocyte's infiltration.In addition, luteolin also has the PDE of inhibition, anti-SARS, HIV virus characteristic except antiinflammatory, the anti-allergic effects.
The present invention; Show that through zoopery luteolin can reduce the increase of cholesterol and triglyceride in the blood, reduce the synthetic of triglyceride in the liver; Thereby blocked the source of lipid accumulation in the liver, being used for treating the fatty liver medicine in preparation will have been widely used.
Beneficial effect: be used to treat the fatty liver medicine and compare with existing; The outstanding advantage that luteolin kind treatment fatty liver medicine of the present invention has comprises: show through zoopery; Luteolin can reduce the content of cholesterol and triglyceride in the blood; Triglyceride is synthetic in the minimizing liver, thereby has blocked the source of lipid accumulation in the liver, and being used for treating the fatty liver medicine in preparation will have been widely used; Have good practicability, can produce favorable economic benefit and social benefit.
Description of drawings
Fig. 1 is the lipids contents figure after the mice administration intervened for 8 weeks;
Fig. 2 is the content of triglyceride figure in the liver after the mice administration intervened for 8 weeks;
Fig. 3 is that the random blood sugar of respectively organizing mice contains spirogram;
Fig. 4 is the carbohydrate tolerance figure as a result that respectively organizes behind the mice fasting 12h;
Fig. 5 is a characteristic pattern of respectively organizing mouse liver after 8 weeks of administration intervention;
Fig. 6 is glycogen figure (C) and fatty tissue figure (D) in the ultrasonic image figure (A) that respectively organizes mouse liver after 8 weeks of administration intervention, the lipid figure (B) in the liver, the liver;
Fig. 7 is the expression of results figure that detects the synthetic rate-limiting enzyme of fatty acid through western blot method;
Fig. 8 influences figure as a result during to be luteolin to the lipid of human hepatoma cell line HepG2 and mice primary hepatocyte synthetic.
The specific embodiment
Below in conjunction with specific embodiment the present invention is done further explanation.
Embodiment 1
(1) luteolin is available from Nat'l Pharmaceutical & Biological Products Control Institute, and the spontaneous animal model db/db of non-alcoholic fatty liver mice is available from model animal institute of Nanjing University.
(2) experimental group db/db mice: male, in 6 ages in week, body weight 28 ~ 33g/ only; Divide into groups: totally 18, be divided into 3 groups at random, 6 every group.Brood negative mice (C57BL/KsJ): male, in 6 ages in week, body weight 18 ~ 22g/ only; Divide into groups: totally 6, as matched group.
(3) administration is handled: intraperitoneal injection, was administered once, and continued medication for 6 ~ 8 weeks in per two days by 20mg/kg/ or 100mg/kg/.
(4) collection of blood sample: the eye corner of the eyes is got blood, places the dry 0.5ml EP pipe of heparin sodium anticoagulant, 3000r/min, and centrifugal 5min, every mice is got serum 20ul at every turn, is used for the detection of mice blood fat.Lipids contents is as shown in Figure 1 as a result, and content of triglyceride is as shown in Figure 2.The db/db mice is as the animal model of a spontaneous obesity, and cholesterol in the blood and triglyceride are that significance increases.After db/db mice successive administration is intervened, in the conventional sense of the blood fat that carries out, find that luteolin can reduce the increase of cholesterol and triglyceride in the blood, the while has also been blocked the source of lipid accumulation in the liver.
(5) mensuration of blood glucose:, adopt the safe and reliable blood glucose meter of Abbott Laboratories to carry out the detection of mouse blood sugar through the blood sampling of tail vein Wicresoft.It is as shown in Figure 3 to measure the random blood sugar result.Because the db/db mice is spontaneous hyperglycemia model, excessively absorbs the sugar content food with high and also can cause fat.Through detecting the effect experiment of luteolin to the db/db mouse blood sugar; The result shows that luteolin can increase the picked-up of glucose; And this part takes in intravital glucose and is stored in the liver with the form of glycogen, do not have a large amount of fat that is converted into, and the control group mice result is opposite.
(6) abdominal cavity glucose tolerance experiment: adopt method, the situation of change of the mouse blood sugar when back 0,15,30,60 and 120min are injected in monitoring respectively through lumbar injection 2g/kg glucose.The carbohydrate tolerance result is as shown in Figure 4.
In the process that continues medication, also repeatedly observe the in vivo development of fatty liver through toy B ultrasonic appearance, the while, during 8 weeks, the liver and the fat that take out mice carried out section detection and liver albumen western detection in administration.
(7) B-mode ultrasonography of mouse liver: select for use VEVO2100 toy Ultrasound Instrument to carry out the real-time diagnosis and the monitoring of live body fatty liver;
(8) the oil red O of liver and haematoxylin complex staining: with D-hanks that sample cell or tissue slice flushing is abundant earlier; Add oil red dilution dyeing 10 ~ 15 minutes then; Next with 75% alcoholic solution that matter between sample differentiation extremely is clear; Distilled water dashes then, and last reuse haematoxylin pair cell nuclear part is redyed, and under 100 times of mirrors, observes and take pictures.Take pictures observation to investigate the effect of lipid accumulation with every group of sample picked at random 5 ~ 10 visuals field.
(9) the glycogen color of liver: the liver specimens section, with periodic acid-SchiffShi method (PAS) row hepatic glycogen dyeing, mirror is observed section down, takes pictures with every group of sample picked at random 5 ~ 10 visuals field and observes to investigate content of glycogen in the liver.
(10) haematoxylin-Yihong of fatty tissue (HE) dyeing: as for 60 ℃ of baking oven 45s, 95% alcohol fixation behind the haematoxylin dyeing 15min, is carried out the hydrochloride alcohol differentiation with the fatty tissue section, and room temperature is returned blue 10min, Yihong dyeing 5min, dehydration, mounting.
(11) Western bolt: with the fresh liver BIAO and BEN that takes out, put in people's liquid nitrogen, go to-80 ℃ of preservations.With organizing cracking process to extract-20 ℃ of preservations behind the albumen, with Coomassie brilliant blue method measurement protein concentration.PAGE adopts 39 g/L to concentrate glue, 100 g/L separation gels; Applied sample amount 50 μ g, albumen Marker 5 μ L, voltage 60 V treat to transfer to 120 V after albumen is run out of concentrated glue; Electrophoresis finishes the back and takes out gel, with Quantity One software analysis OD value.
In the process that continues medication, repeatedly observe the in vivo development of fatty liver through toy B ultrasonic appearance, the while, during 8 weeks, the liver and the fat that take out mice carried out section detection and liver albumen western detection in administration.The characteristic pattern of respectively organizing mouse liver after 8 weeks of administration intervention is as shown in Figure 5, and it is as shown in Figure 6 respectively to organize mouse liver each item detection index after 8 weeks of administration intervention, and wherein A figure is a ultrasonic image, and B figure is the lipid in the liver, and C figure is a glycogen in the liver, and D figure is a fatty tissue; Through the expression of lipogenesis GAP-associated protein GAP in the western blot method detection mouse liver, the result is as shown in Figure 7; Each experimental result shows that luteolin can reduce the expression and the athero of the fatty acid synthesis related gene in the db/db mouse liver, the idiopathic fatty liver of the improvement of significance.
Embodiment 2
The separation of primary hepatocyte and cultivation: the pentobarbital sodium of C57BL/KsJ mouse peritoneal injection 1% is carried out anaesthetic treatment; From the portal catheterization of mice and after being interrupted postcava; Pour into Kreb solution with the 2ml/min flow velocity; After treating that the interior blood of liver is rinsed well, continue to pour into collagenase IV 30ml with the 2ml/min flow velocity.After treating that liver fully digests, piece of tissue is shredded, add DMEM complete culture solution 50ml and stop digestion and abundant mixing, filter with 200 mesh.With the centrifugal 5min of 50G/min, concentrate hepatocyte.
In order to observe comparatively significantly fat accumulation at cellular level, adopted liver X receptor agonist T0901317 that HepG2 cell and mice primary hepatocyte are handled in advance, after handling 48h, carried out the plain – oil red dyeing of Su Mu.Experimental result is as shown in Figure 8, and the result shows that agonist T1317 can activate the activity of liver X receptor, raises the fatty acid synthesis related gene in downstream, thereby the content of intracellular fatty acid and triglyceride is increased.But in the observation process, obviously be less than the T1317 processed group through luteolin and the common intracellular lipid content of handling of agonist T1317.Explained that the lipid that luteolin can reduce in the liver cell synthesizes.
Compare with the medicine of treatment fatty liver with existing prevention, the native compound luteolin has remarkable advantages, and drug effect is obvious, toxic and side effects is little.
Claims (2)
1. luteolin is used for treating the application of fatty liver medicine in preparation.
2. medicine that is used to treat fatty liver, it is characterized in that: effective ingredient is a luteolin.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011104308732A CN102552238A (en) | 2011-12-21 | 2011-12-21 | New application of luteolin |
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| CN2011104308732A CN102552238A (en) | 2011-12-21 | 2011-12-21 | New application of luteolin |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016141682A (en) * | 2015-02-03 | 2016-08-08 | ウィンテック コーポレイションＷｙｎｔｅｋ Ｃｏｒｐｏｒａｔｉｏｎ | Pharmaceutical compositions for treating hypertriglyceridemia or for reducing risk of developing hypertriglyceridemia |
| CN106172879A (en) * | 2016-07-18 | 2016-12-07 | 马鞍山市黄池食品（集团）有限公司 | A kind of luteolin Semen Sesami gel oil and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1493571A (en) * | 2003-08-25 | 2004-05-05 | 杭州福斯特化学品有限公司 | Luteolin metal salt and its preparation method and use |
| WO2006135084A1 (en) * | 2005-06-14 | 2006-12-21 | Kurume University | Prophylactic or therapeutic agent for steatohepatitis or fatty liver |
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2011
- 2011-12-21 CN CN2011104308732A patent/CN102552238A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1493571A (en) * | 2003-08-25 | 2004-05-05 | 杭州福斯特化学品有限公司 | Luteolin metal salt and its preparation method and use |
| WO2006135084A1 (en) * | 2005-06-14 | 2006-12-21 | Kurume University | Prophylactic or therapeutic agent for steatohepatitis or fatty liver |
Non-Patent Citations (3)
| Title |
|---|
| JIN-FENG LIU,ET AL: "《Reduction of Lipid Accumulation in HepG2 Cells by Luteolin is associated with Activation of AMPK and Mitigation of Oxidative Stress》", 《PHYTOTHERAPY RESEARCH》 * |
| 石亚中，伍亚华: "《花生壳综合利用研究现状》", 《花生学报》 * |
| 韩炜，邢燕，康廷国: "《木犀草素生物活性研究进展》", 《云南中医中药杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016141682A (en) * | 2015-02-03 | 2016-08-08 | ウィンテック コーポレイションＷｙｎｔｅｋ Ｃｏｒｐｏｒａｔｉｏｎ | Pharmaceutical compositions for treating hypertriglyceridemia or for reducing risk of developing hypertriglyceridemia |
| CN106172879A (en) * | 2016-07-18 | 2016-12-07 | 马鞍山市黄池食品（集团）有限公司 | A kind of luteolin Semen Sesami gel oil and preparation method thereof |
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Application publication date: 20120711 |