CN101549039B - Application of schisandra fruit or related monomeric compound thereof for preventing or curing fatty liver - Google Patents
Application of schisandra fruit or related monomeric compound thereof for preventing or curing fatty liver Download PDFInfo
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Abstract
The invention discloses an application of schisandra fruit, schisandra fruit monomeric compound or other related artificially synthesized monomeric compounds (bifendate or bicyclol) during the preparation of a drug for preventing and curing the fatty liver. The experiments show that the schisandra fruit extract or the related monomeric compound (Gamma-schizandrin, bifendate or bicyclol) thereof can effectively reduce the content of the triglyceride and the total cholesterol of the liver of the fatty liver model animal, and the medicament is especially suitable for curing the fatty liver patients with low blood fat level.
Description
Technical field
The present invention relates to a kind of novel medical use of a kind of plant extract or its relevant monomeric compound, relate in particular to Fructus Schisandrae Chinensis extrat or the purposes of its relevant monomeric compound in prevention or treatment fatty liver, belong to the field of Chinese medicines.
Background technology
Fructus Schisandrae Chinensis is the mature fruit of Magnoliaceae perennial fallen leaves bejuco Fructus Schisandrae Chinensis Schisandra chinensis (Turcz.) Baill. or schisandra chinensis Schisandra sphenanthera Rehd.et Wils..The former practises title " Radix Schisandrae Bicoloris ", and main product is in northeast; The latter practises title " Fructus Schisandrae Sphenantherae ", and main product is in southwest and on the south the Yangtze river basin.Main volatile oil, organic acid, tannin, vitamin, sugar and the resin etc. of containing.Main component in the seed volatile oil is a schizandrin, mainly contains cyclohexyl biphenyl octene class material, and deoxyschizandrin is arranged, and second is plain, third element, and pure first (schizandrin), pure second and ester first,, and the third, fourth, penta; Also contain volatile oil, be mainly monoterpenes, sesquiterpenoids, hendecanone etc.Other still contains organic acid, vitamin A, vitamin E and polysaccharide etc.Up to now, the main pharmacological effect of the Fructus Schisandrae Chinensis of finding is following:
1, the central nervous system had sedation.2, hepatoprotective effect: Chinese Magnoliavine Fruit alcohol extract and deoxyschizandrin, second element, third element, pure first, pure second, ester first, ester the second grade have the significant protection effect to the animal liver cell damage that chemical toxicant causes; Can suppress transaminase's release, make the active reduction of ALT in the blood.Obviously inducing mouse and rat liver microsomes cytochrome P-450 are active.Increase the liver detoxification ability.3, blood vessel dilating effect.4, delaying senility function.5, have and eliminate the phlegm and antitussive effect.6, to lymphocyte DNA is synthetic facilitation is arranged, lymphoblast is generated increase, and promote the spleen immunologic function.7, antiulcer action.
Bifendate: be synthetic schisandrin C analog, can safeguard that liver plasma membrane is complete, alleviate poisonous substance, have and obviously fall the aminotransferase effect, and can improve cardinal symptoms such as the pain in the hepatic region of hepatitis, weak, abdominal distention to hepatocellular infringement.
Bicyclol (trade name hundred match promises): be bifendate similar medicine, its chemical name is 4,4 '-dimethoxy-5,6, and 5 ', 6 '-two (methylene-dioxy)-2-methylols-2 '-methoxycarbonyl group joins.The aminotransferase of the chmice acute hepatic injury that bicyclol causes carbon tetrachloride, D-Gal amine, acetaminophen raises, the aminotransferase of mouse immune hepatitis raises has the reduction effect, and the infringement of liver organization pathomorphology has alleviating in various degree.The in vitro tests result shows that the 2.2.15 cell strain to HCC transfection human hepatitis B virus has the HBeAg of inhibition, HBV-DNA, the excretory effect of HBsAg.Bicyclol maybe be through regulating certain signaling mechanism of body, or transfer the body specific immune function and play a role, and apoptosis appears in the hepatocyte of inductive infection hepatitis virus, to reach the effect that suppresses virus replication, hepatocellular apoptosis is then played a protective role.At present, bicyclol is clinical to be used to treat chronic viral hepatitis B, hepatitis C, and it protects the liver and antivirus action is confirmed.
Up to now, there are not Fructus Schisandrae Chinensis, bifendate and bicyclol to have the relevant report that reduces fatty liver animal pattern liver tg and cholesterol effect as yet.
Investigation of clinical epidemiology shows, the change of Along with people's living habit and dietary structure, and clinical B ultrasonic development of technology and extensive use, and the recall rate of fatty liver is increasing in recent years, and sickness rate is in rising trend.Fatty liver is meant the pathological changes of fatty overheap in the hepatocyte that causes owing to a variety of causes, and causes liver inflammatory reaction, fibrosis, liver cirrhosis on this basis, even canceration.Generally speaking, fatty liver belongs to the reversibility disease, and early diagnosis and treatment in time often can recover normal.Total fat amount in normal person's the liver, account for liver heavy 5%, include phospholipid, triglyceride, fat acid, cholesterol and cholesterol ester etc.And the person of suffering from fatty liver, total fat amount can reach 40%-50%, mainly is triglyceride and fat acid, increases and phospholipid, cholesterol and cholesterol ester are only a small amount of.In certain areas, fatty liver has become the second largest hepatopathy that is only second to viral hepatitis.In China, the sickness rate of fatty liver is 8-10%, and the sickness rate of Beijing is 26%, and Shanghai City is 30%.In the U.S., the sickness rate of fatty liver is 10-15%, and the sickness rate of fatty liver is 50% in fat and diabetics, in known easy trouble factor, is followed successively by obesity (69%), hyperlipemia (56%), drinks (44%) and diabetes (17%).At present, fatty liver divides two types of ethanol property and non-ethanol, and is wherein in the majority with non-alcoholic fatty liver disease, in the Shanghai City, China, and the artificial non-alcoholic fatty liver disease of 90% fatty liver.
In the alcohol fatty hepatopath, have only few part patient blood fat possibly occur and increase.Non-alcoholic fatty liver disease, its reason more complicated comprises obesity, diabetes, hyperlipidemia, medicine and inherited genetic factors etc., also has about 40% to be agnogenic fatty liver.In the non-alcoholic fatty liver disease patient, also have only groups of people's blood fat to raise.Obviously, the Patients with Fatty Liver that blood fat is not high is taken hypolipidemic, and the treatment fatty liver is had no meaning.Even Patients with Fatty Liver with hyperlipidemia, can not be used hypolipidemic rashly.This be because; Most hypolipidemics can impel the lipid in the blood to focus on liver and carry out metabolism, and just there is lipodystrophy originally in the liver of having suffered from fatty liver, and the lipid that from blood, bursts upon is difficult to handle more; Can only it be deposited in the liver once again, this undoubtedly can the weight fat liver.In addition, doctors also observe, and pylephlebitis, portal vein fibrosis on every side can take place the person to abuse the hypolipidemic for a long time, even can promote that fatty liver develops to liver cirrhosis.
Up to the present, still there is not lipotropic active drug.General normal protection hepatocyte, degrease medicine and the antioxidant etc. selected for use; Like vitamin B, C, E, lecithin, ursodesoxycholic acid, silymarin, inosine, coenzyme A, reduced glutathion, taurine, carnitine Orotate, glucuronolatone, and some fat-reducing medicament or the like.Though said medicine is a lot, still need further its curative effect of checking and safety mostly.Therefore, the research and development of treatment fatty liver medicine more and more receive people's attention, yet up to the present also do not find the medicine of a species specific treatment fatty liver.Mostly those are hypolipidemic to the medicative medicine of fatty liver at present, promptly reach the purpose of treatment fatty liver through the effect of blood fat reducing, can produce injury effect to liver function after this type medicine is taken for a long time.
Summary of the invention
A kind of new purposes that the purpose of this invention is to provide five tastes of medicinal herb son and relevant monomeric compound (schisandrin B, bifendate and bicyclol) thereof, promptly these chemical compounds are as the new purposes of medicine in treatment fatty liver and lipid metabolism are studied.
The inventor finds through lot of test; The allied compound of the synthetic that monomeric compound in five tastes of medicinal herb seed extract, the Fructus Schisandrae Chinensis extrat or Fructus Schisandrae Chinensis are relevant; Can reduce the triglyceride and the total cholesterol level of fatty liver animal pattern liver; And when reducing the liver lipid rapidly, do not influence the blood fat of animal pattern.
Described five tastes of medicinal herb seed extract is preferably ethanol extraction; Described schisandra chinensis ethyl hydrate extract can prepare according to the method that various document is put down in writing; These all are technology well-known to those skilled in the art; In addition, schisandra chinensis ethyl hydrate extract also can be bought through various commercial sources and obtain.
As a reference, schisandra chinensis ethyl hydrate extract also can prepare according to following method: get Fructus Schisandrae Chinensis 500g, fragmentation; Extract at twice with 80% ethanol 5000ml then; Merge extracted twice liquid, filtration, water-bath are condensed into 250ml (every ml contains crude drug 2g), and it is subsequent use to put 4 ℃ of refrigerators.
The monomeric compound of described Fructus Schisandrae Chinensis extrat is preferably deoxyschizandrin, schisandrin B, schisandrin C; Schisandrin B more preferably;
The allied compound of the synthetic that described Fructus Schisandrae Chinensis is relevant is bifendate or bicyclol (commodity " hundred match promises " by name).
The present invention utilizes Fructus Schisandrae Chinensis extrat, and (schisandrin B, bifendate or bicyclol treatment fatty liver have following advantage: 1) rapid-action with relevant monomeric compound; 2) reduction liver tg and cholesterol effect are obvious; 3) when reducing the liver lipid, do not influence the blood fat of animal pattern.So side effects of pharmaceutical drugs of the present invention are little, be particularly suitable for treating the not high Patients with Fatty Liver of blood lipid level.
The specific embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage of the present invention and characteristics will be more clear along with description.But these embodiment only are exemplary, scope of the present invention are not constituted any restriction.What those skilled in the art should understand that is; Down can make amendment with form or replace (like the method for distilling that changes Fructus Schisandrae Chinensis extrat, the molecular structure that changes allied compound etc.) without departing from the spirit and scope of the present invention, but these modifications and replacing all fall in protection scope of the present invention the details of technical scheme of the present invention.
Test Example 1 schisandra chinensis ethyl hydrate extract reduces the lipid content of fatty liver model mice liver
One, experiment material
Laboratory animal: the ICR mice, male, body weight 25-30g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., animal quality certification SCXK (capital) 2002-0003.Normal mouse is fed with conventional feed, and the fatty liver model mice is fed with high fat/cholesterol feed, and wherein Adeps Sus domestica content is 10% (W/W), and cholesterol level is 1% (W/W).
Fructus Schisandrae Chinensis extrat: Fructus Schisandrae Chinensis is purchased in Anguo Chinese crude drug wholesale market, through being accredited as Radix Schisandrae Bicoloris.Get Fructus Schisandrae Chinensis 500g, fragmentation is extracted with 80% ethanol 5000ml then at twice, merges extracted twice liquid, filters, water-bath is condensed into 250ml (every ml contains crude drug 2g), and it is subsequent use to put 4 ℃ of refrigerators.
Other medicines and reagent: cholesterol is purchased the chemical reagents corporation in Beijing; Luxuriant and rich with fragrance nobert is purchased the pharmaceuticals in Yongkang, Beijing; Triglyceride and T-CHOL are measured test kit and are purchased the biochemical reagent company in north.
Two, experimental technique and result
Mice uses schisandra chinensis ethyl hydrate extract 0.5ml/kg (being equivalent to crude drug 1g/kg) and 2.5ml/kg (being equivalent to crude drug 5g/kg) to irritate stomach, every day 1 time, continuous 7 days respectively after feeding 7 days with high fat/cholesterol feed.The positive drug group is with luxuriant and rich with fragrance nobert 0.1g/kg (preparing with 0.5%CMC), and normal and not administration model group mice is irritated stomach with 0.5%CMC (carboxymethyl cellulose) 10ml/kg.Several 10 of every treated animal.After last administration 24 hours, get liver, weigh, homogenate, centrifugal, get supernatant and measure hepatic tissue triglyceride and total cholesterol level.Experimental result finds that schisandra chinensis ethyl hydrate extract can reduce fatty liver model mice liver cholesterol and triglyceride levels.The result sees table 1.
The effect of table 1. Fructus Schisandrae Chinensis extrat reduction fatty liver animal pattern liver lipid content (mean ± SEM)
| Group | Dosage (g/kg) | Liver triglyceride (μ mol/g) | Liver T-CHOL (μ mol/g) |
| Normal group | 2.997±0.262 | 2.164±0.184 | |
| Model group | 18.828±1.729* | 5.736±0.522* | |
| Model+schisandra chinensis ethyl hydrate extract | 1 | 7.285±1.307 # | 2.046±0.234 # |
| Model+schisandra chinensis ethyl hydrate extract | 5 | 12.324±1.742 # | 6.849±0.718 |
| Model+luxuriant and rich with fragrance nobert | 0.1 | 14.077±0.974 # | 5.492±0.321 |
*P＜0.05 is with the normal group ratio;
#P＜0.05 is with fatty liver model group ratio.
Test Example 2 schisandrin Bs reduce the lipid content of fatty liver model mice liver
One, experiment material
Laboratory animal: the ICR mice, male, body weight 25-30g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., animal quality certification SCXK (capital) 2002-0003.Normal mouse is fed with conventional feed, and the fatty liver model mice is fed with high fat/cholesterol feed, and wherein Adeps Sus domestica content is 10% (W/W), and cholesterol level is 1% (W/W).
Schisandrin B: provided by Hong Kong University of Science and Thchnology, purity is greater than 95%.
Other medicines and reagent: cholesterol is purchased the chemical reagents corporation in Beijing; Luxuriant and rich with fragrance nobert is purchased the pharmaceuticals in Yongkang, Beijing; Triglyceride and T-CHOL are measured test kit and are purchased the biochemical reagent company in north.
Two, experimental technique and result
Mice was fed 7 days with high fat/cholesterol feed, used schisandrin B 0.05,0.1,0.2g/kg simultaneously respectively, and luxuriant and rich with fragrance nobert 0.1g/kg irritates stomach, every day 1 time, continuous 6 days.Several 10 of every treated animal.Medicine is prepared with olive oil.Normal and not administration model group mice is irritated stomach with olive oil 10ml/kg.After last administration 24 hours, get liver, weigh, homogenate, centrifugal, get supernatant and measure hepatic tissue triglyceride and total cholesterol level.Experimental result finds that five tastes second have the effect that reduces fatty liver model mice liver cholesterol and triglyceride.The result sees table 2.
The effect of table 2. schisandrin B reduction fatty liver animal pattern liver lipid content (mean ± SEM)
| Group | Dosage (g/kg) | Liver triglyceride (μ mol/g) | Liver T-CHOL (μ mol/g) |
| Normal group | 2.746±0.246 | 1.924±0.135 | |
| Model group | 4.664±0.193 * | 3.771±0.156 * |
| Model+schisandrin B | 0.05 | 3.768±0.193 | 3.635±0.147 |
| Model+schisandrin B | 0.1 | 2.322±0.195 # | 2.856±0.121 # |
| Model+schisandrin B | 0.2 | 3.223±0.439 # | 2.596±0.226 # |
| Model+luxuriant and rich with fragrance nobert | 0.1 | 2.438±0.393 # | 2.426±0.147 # |
*P＜0.05 is with the normal group ratio;
#P＜0.05 is with fatty liver model group ratio.
Test Example 3 bifendate reduce the lipid content of fatty liver model mice liver
One, experiment material
Laboratory animal: the ICR mice, male, body weight 25-30g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., animal quality certification SCXK (capital) 2002-0003.Normal mouse is fed with conventional feed, and the fatty liver model mice is fed with high fat/cholesterol feed, and wherein Adeps Sus domestica content is 10% (W/W), and cholesterol level is 1% (W/W).
Bifendate: the Beijing XieHe medicine Factory produces.
Other medicines and reagent: cholesterol is purchased the chemical reagents corporation in Beijing; Luxuriant and rich with fragrance nobert is purchased the pharmaceuticals in Yongkang, Beijing; Triglyceride and T-CHOL are measured test kit and are purchased the biochemical reagent company in north.
Two, experimental technique and result
Mice was fed 10 days with high fat/cholesterol feed, and the 6th to the 9th day, treatment group mice was irritated stomach with bifendate 0.03,0.1,0.3g/kg respectively, every day 1 time.The positive drug group is irritated stomach with luxuriant and rich with fragrance nobert 0.1g/kg.Medicine is prepared with 0.5%CMC.Normally and do not treat the model group mice and irritate stomach with 0.5%CMC 10ml/kg.Several 10 of every treated animal.After last administration 24 hours, get liver, weigh, homogenate, centrifugal, get supernatant and measure hepatic tissue triglyceride and total cholesterol level.Experimental result finds that bifendate has the effect that reduces fatty liver model mice liver cholesterol and triglyceride.The result sees table 3.
The effect of table 3. bifendate reduction fatty liver animal pattern liver lipid content (mean ± SEM)
| Group | Dosage (g/kg) | Liver triglyceride (μ mol/g) | Liver T-CHOL (μ mol/g) |
| Normal group | 9.30±0.79 | 3.57±0.18 | |
| Model group | 19.39±0.90 * | 13.14±0.44 * | |
| Model+bifendate | 0.03 | 14.27±0.74 # | 10.19±0.64 # |
| Model+bifendate | 0.1 | 15.45±0.85 # | 9.60±0.43 # |
| Model+bifendate | 0.3 | 13.91±0.75 # | 8.22±0.36 # |
| Model+luxuriant and rich with fragrance nobert | 0.1 | 11.02±0.76 # | 5.63±0.43 # |
*P＜0.05 is with the normal group ratio;
#P＜0.05 is with fatty liver model group ratio.
Test Example 4 bicyclols reduce the lipid content of fatty liver model mice liver
One, experiment material
Laboratory animal: the ICR mice, male, body weight 25-30g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., animal quality certification SCXK (capital) 2002-0003.Normal mouse is fed with conventional feed, and the fatty liver model mice is fed with high fat/cholesterol feed, and wherein Adeps Sus domestica content is 10% (W/W), and cholesterol level is 1% (W/W).
Bicyclol: the Beijing XieHe medicine Factory produces; Chemical name is 4,4 '-dimethoxy-5,6,5 ', 6 '-two (methylene-dioxy)-2-methylols-2 '-methoxycarbonyl group joins.
Other medicines and reagent: cholesterol is purchased the chemical reagents corporation in Beijing; Luxuriant and rich with fragrance nobert is purchased the pharmaceuticals in Yongkang, Beijing; Triglyceride and T-CHOL are measured test kit and are purchased the biochemical reagent company in north.
Two, experimental technique and result
Mice was fed 8 days with high fat/cholesterol feed, and the mice of treatment group is simultaneously used bicyclol 0.1,0.3g/kg respectively, or luxuriant and rich with fragrance nobert 0.1g/kg irritates stomach.Every day 1 time, continuous 7 days.Medicine is prepared with 0.5%CMC.Normally and do not treat the model group mice and irritate stomach with 0.5%CMC 10ml/kg.Several 10 of every treated animal.After last administration 24 hours, get liver, weigh, homogenate, centrifugal, get supernatant and measure hepatic tissue triglyceride and total cholesterol level.The result finds that bicyclol has the effect that reduces fatty liver model mice liver cholesterol and triglyceride.The result sees table 4.
The effect of table 4. bicyclol reduction fatty liver animal pattern liver lipid content (mean ± SEM)
| Group | Dosage (g/kg) | Liver triglyceride (μ mol/g) | Liver T-CHOL (μ mol/g) |
| Normal group | 4.730±0.088 | 2.766±0.108 | |
| Model group | 13.860±1.452 * | 4.602±0.420 * | |
| Model+bicyclol | 0.1 | 6.000±0.667 # | 3.053±0.285 # |
| Model+bicyclol | 0.3 | 4.520±0.813 # | 3.409±0.223 # |
| Model+luxuriant and rich with fragrance nobert | 0.1 | 4.339±0.910# | 2.479±0.258 # |
*P＜0.05 is with the normal group ratio;
#P＜0.05 is with fatty liver model group ratio.
Claims (1)
1. schisandra chinensis ethyl hydrate extract or schisandrin B are as the purposes in the medicine of unique active component lipid content in preparation reduction liver.
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104490896A (en) * | 2014-11-27 | 2015-04-08 | 上海中医药大学 | Pharmaceutical use of protopanaxatriol or/and derivatives thereof |
| CN106994122A (en) * | 2016-01-26 | 2017-08-01 | 中国人民解放军军事医学科学院毒物药物研究所 | The purposes of schizandrin A anti-hepatic fibrosis |
| CN105748463A (en) * | 2016-02-05 | 2016-07-13 | 上海中医药大学 | Pharmaceutical application of schisandra lignan compound |
| CN112755192A (en) * | 2019-10-21 | 2021-05-07 | 北京协和药厂 | Application of bicyclol compounds in preparation of medicines for preventing or treating atherosclerotic diseases and pharmaceutical composition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1256125A (en) * | 1999-12-01 | 2000-06-14 | 潘思源 | New application of schisandra essence |
| CN101073602A (en) * | 2006-05-15 | 2007-11-21 | 成都地奥九泓制药厂 | Medicinal composition for treating or improving liver function, its production and use |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1256125A (en) * | 1999-12-01 | 2000-06-14 | 潘思源 | New application of schisandra essence |
| CN101073602A (en) * | 2006-05-15 | 2007-11-21 | 成都地奥九泓制药厂 | Medicinal composition for treating or improving liver function, its production and use |
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| 刘耕陶等.五味子有效成分对动物肝脏药理作用研究的近况.《中西医结合杂志》.1983,第3卷(第3期),182-185. * |
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| 汤臣康.五味子的化学和药理研究的新进展.《西北药学杂志》.1994,第9卷(第6期),278-282. * |
| 王良骏等.五味子在肝病中的运用.《中西医结合肝病杂志》.1997,第7卷(第3期),185-188. * |
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