CN103381173B - The pharmaceutical applications of Folium Ilicis saponin D - Google Patents
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Abstract
The invention provides the pharmaceutical applications as shown in the formula the Folium Ilicis saponin D shown in (I), particularly Folium Ilicis saponin D for the preparation of the purposes prevented and/or treated in dyslipidemia associated diseases and the/medicine of disease.
Description
Technical field
The invention belongs to pharmaceutical technology sectors.Specifically, the present invention relates to a kind of application of Folium Ilicis saponin D.
Background technology
Hyperlipemia mainly comprises hypercholesterolemia and hypertriglyceridemia, and the former hazardness is far away higher than the latter.For hyperlipemia, Drug Comprehensive Therapy for Correcting Lipidemia is the most effective measures for the treatment of hyperlipemia.At present, reduce the active drug of triglyceride a lot, but the active drug reducing cholesterol is still mainly Statins at present.Such drug main will to the arteriosclerosis caused by anti-hypercholesterolemiccompounds, and its mechanism of action is for suppressing hepatic cholesterol synthesis.But long-term taking statins has obvious toxic action to liver and muscle, cause transaminase to increase simultaneously, there is rhabdomyolysis and acute renal failure in minority user, although have passed through the modification of several generations medicines structure, and still its toxic and side effects problem unresolved.Therefore, there is the demand to new medicine.
Folium Ilicis is the traditional beverage among the people of China, and what the health tea as functions such as fat-reducing, blood fat reducing, blood pressure lowering, heat-clearing and toxic substances removing had nearly one thousand years drinks history.The present inventor's research in earlier stage finds that ilexlutifolia thumb total saponin has and well reduces the effect such as blood fat, atherosclerosis (Chinese patent application CN201110026026.X).By the chemical constitution study to total saponins position, be therefrom separated and obtain more than 30 compounds, be mainly saponin and a small amount of flavone compound.
Summary of the invention
The present inventor is through carrying out screening system to be separated in Folium Ilicis more than 30 compounds, find Folium Ilicis saponin component, especially Folium Ilicis saponin D (3-O-β-D-glucopyranosyl-(1 → 3)-[-α-L-rhamnopyranosyl (1 → 2)]-α-L-arabinofuranosyl-α-Herba Lactucae formosanae lactone, Folium Ilicis saponin D or saponin D is called in literary composition) there is blood fat reducing, study of anti-atherogenic effect, for the principle active component of Folium Ilicis blood fat reducing and study of anti-atherogenic effect, its action intensity is suitable with statins, but its mechanism and statins are completely different.In addition, this compound reduces the effect such as triglyceride, antioxidation in addition.Study on mechanism shows, Folium Ilicis saponin D blood fat reducing mechanism is for suppressing cholesterol intestinal absorption.Therefore Folium Ilicis saponin D may be used for the medicine preparing treatment hyperlipidemia and relevant disease and disease.
Therefore the object of the invention is to, provide Folium Ilicis saponin D for the preparation of the purposes prevented and/or treated in dyslipidemia associated diseases and the/medicine of disease.
For foregoing invention object, the invention provides following technical scheme:
The invention provides Folium Ilicis saponin D for the preparation of the purposes prevented and/or treated in dyslipidemia associated diseases and the/medicine of disease.
Wherein Folium Ilicis saponin D structure is as shown in the formula shown in (I):
Wherein,
Wherein, described disease and/disease are selected from one or more in hypercholesterolemia, hypertriglyceridemia, atherosclerosis, the injury of kidney caused by hyperlipemia and relevant disease thereof and disease.
Preferably, described disease and/disease are selected from one or more in hypertriglyceridemia, hypercholesterolemia and atherosclerosis and relevant disease thereof and disease;
Further preferably, described disease and/disease are selected from one or more in hypertriglyceridemia, hypercholesterolemia and atherosclerosis.
The medicine adopting Folium Ilicis saponin D to prepare can be used alone, also can with statins conbined usage, to improve drug effect and to improve the toxic and side effects of statins.
Existing many sections of documents disclose the preparation of Folium Ilicis saponin D.People (the OuyangMA such as such as OuyangMA, YangCR, ChenZL, WangHQ.Triterpenesandtriterpenoidglycosidesfromtheleaves ofIlexkudingcha.Phytochemistry.1996,41 (3): 871-877) disclosed method.
The present inventor is found by large quantity research, and Folium Ilicis saponin D can reduce the level of T-CHOL in blood plasma, total triglyceride, plasma high density lipoprotein level, increases the amount of lipid in feces simultaneously.By on the research of Folium Ilicis saponin in the affecting of small intestinal gene expression, find that Folium Ilicis saponin can suppress cholesterol intestinal absorption key enzyme (ABCG8) and the expression of the key enzyme (ACAT2) of synthetic cholesterol in intestinal, thus suppress cholesterol intestinal absorption, effectively lower blood lipid level.This mechanism of action is different from the statins of current extensive use, but action intensity is suitable with statins.In addition, this compound reduces triglyceride, antioxidation, kidney protection in addition, improves the effects such as hemorheology.
Accompanying drawing explanation
Hereafter will describe embodiments of the invention in detail in conjunction with following accompanying drawing:
Fig. 1 is the impact of Folium Ilicis saponin D on ApoE-/-mice plasma total cholesterol level; Wherein, CD is that normal diet is fed; HD is that high fat diet is fed; W1 is after administration 1 week; W2 is after administration 2 weeks; W3 is after administration 3 weeks; W4 is after administration 4 weeks; In figure, data are meansigma methods ± SEM.
Fig. 2 is the impact of Folium Ilicis saponin D on ApoE-/total triglyceride levels of-mice plasma; Wherein, CD is that normal diet is fed; HD is that high fat diet is fed; W1 is after administration 1 week; W2 is after administration 2 weeks; W3 is after administration 3 weeks; W4 is after administration 4 weeks; In figure, data are meansigma methods ± SEM.
Fig. 3 is the impact of Folium Ilicis saponin D on ApoE-/-mice plasma hdl level; Wherein, CD is that normal diet is fed; HD is that high fat diet is fed; W1 is after administration 1 week; W2 is after administration 2 weeks; W3 is after administration 3 weeks; W4 is after administration 4 weeks; In figure, data are meansigma methods ± SEM.
Fig. 4 is that Folium Ilicis saponin D is on the impact that ApoE-/-rat aorta is atherosis; Wherein, left side is oil red O stain result, and right side is hematoxylin-eosin staining result; Amplification × 40.
Fig. 5 is that Folium Ilicis saponin D affects statistical result to what ApoE-/-rat aorta was atherosis.* p<0.05vs. height fat matched group, * * p<0.01vs. height fat matched group.
Fig. 6 is the impact of Folium Ilicis saponin D on total cholesterol level in ApoE-/-stool in mice; Wherein, in figure, data are meansigma methods ± SEM,
*p<0.05vs. high fat matched group.
Fig. 7 is the impact that Folium Ilicis saponin D is expressed ApoE-/-mouse small intestine tissue gene; Wherein, in figure, data are meansigma methods ± SEM,
*p<0.05vs. high fat matched group.
Fig. 8 is the impact of Folium Ilicis saponin D on ApoE-/-mice intestinal tissue; Wherein, amplification × 400.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further described in detail, the embodiment provided only in order to illustrate the present invention, instead of in order to limit the scope of the invention.
Experimental technique in following embodiment, if no special instructions, is conventional method.Test material used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop.
Wherein, Folium Ilicis saponin D reference literature preparation (OuyangMA, YangCR, ChenZL, WangHQ.Triterpenesandtriterpenoidglycosidesfromtheleaves ofIlexkudingcha.Phytochemistry.1996,41 (3): 871-877), it is white amorphous powder, is soluble in methanol.Characterization result is as follows:
Liebermann-Burchard and Molish reacting positive, 10% sulphuric acid-ethanol reagent displaing amaranth speckle, shows that compound is triterpene saponin componds.
ESI-MS (m/z): 909 [M+H]
+analyze in conjunction with NMR, infer that its molecular formula is C
47h
72o
17.
1display 7 methyl signals: δ in H-NMR spectrum
h0.82 (3H, s), 0.87 (3H, s), 1.04 (3H, s), 1.09 (3H, s), 1.20 (3H, s), 1.49 (3H, s) and 1.68 (3H, s); Two alkene hydrogen signal: δ
h5.76 (1H, d, J=10.8Hz), 7.49 (1H, dd, J=2.7,10.2Hz); In conjunction with
13one group of carbon signal δ in C-NMR spectrum
c127.2 (C-11), 128.4 (C-12), 140.7 (C-13), 134.9 (C-18); 74.1 (C-19), 85.9 (C-20), 175.2 (C-28), 43.8 (C-17) show that the parent nucleus of this triterpene saponin is α-kudinlactone.
1the terminal hydrogen signal δ of sugar is can be observed in H-NMR spectrum
h4.86 (1H, d, J=5.6Hz), 5.10 (1H, d, J=8.0Hz), 6.17 (1H, br.s);
13sugared end group carbon signal δ is shown in C-NMR spectrum
c101.9,104.7,104.8, be three glucosides in prompting compound.
1can see typical 3 α-H (3.30,1H, dd, J=5.0,14.5Hz) in H-NMR spectrum, prompting Compound C-3 becomes glycosides.After idic acid hydrolysis, TLC inspection is known containing L-arabinose, D-Glucose and L-rhamnose.According to the coupling constant of each monosaccharide
3j
h1-H2judge that arabinose is α configuration, glucose is beta comfiguration, and rhamnose is α configuration.The carbon spectrum of synthesization compound and hydrogen modal data, and carry out full ownership, with bibliographical information (OuyangMA, YangCR, ChenZL, WangHQ.Triterpenesandtriterpenoidglycosidesfromtheleaves ofIlexkudingcha.Phytochemistry.1996,41 (3): 871-877) corresponding data of compound Folium Ilicis saponin D (kudinosideD) coincide, and therefore deterministic compound is Folium Ilicis saponin D.
1H-NMR(pyridine-d
5,500MHz)：δH0.82,0.87,1.04,1.09,1.20,1.49,1.68(3H×7,s,Me-23,Me-24,Me-25,Me-26,Me-27,Me-29,Me-30)，1.63(3H,d,J=8.0Hz,Rha-6-CH
3)，3.30(1H,dd,J=5.0,14.5Hz,H-3)，5.76(1H,d,J=10.5Hz,H-12)，7.49(1H,dd,J=1.7,10.5Hz,H-11)，4.86(1H,d,J=5.6Hz,Ara-1)，5.10(1H,d,J=8.0Hz,Glc-1)，6.17(1H,br.s,Rha-1)。
13c-NMR (pyridine-d
5, 125MHz): data are in table 1.
Compound prepared by table 1 embodiment 1
13cNMR data (pyridine-d
5)
embodiment 1: the effect of Folium Ilicis saponin D
In the present embodiment, demonstrate Folium Ilicis saponin D by different experiments, in blood fat reducing etc., there is good effect.
(1) experiment material and method:
1, experimental animal
C57/BL-ApoE-/-mice comes from Department Of Medicine, Peking University, the animal quality certification number: SCXK capital 2006-0008,6-8 age in week, and body weight 22 ± 2g, male and female half-and-half, are provided by Laboratory Animal Science portion of Department Of Medicine, Peking University.Rearing conditions comprises, temperature: 20 ± 2 DEG C; Humidity: 60 ± 5%; 12 h light and dark cycle; Freely drink water.
2, test grouping and administration
ApoE-/-mice, is divided into 5 groups at random by body weight.
(1) high fat matched group (HG): feeding adds the high lipid food 5 weeks of 0.2% cholesterol and 5% Adeps Sus domestica, every day, gavage gave normal saline simultaneously.
(2) atorvastatin treatment group (AG): feeding high lipid food start after one week gavage give atorvastatin (50mg/kg/d) treatment, every day gavage once, continue to give high fat diet, the course for the treatment of is 4 weeks simultaneously.
(3) Folium Ilicis saponin D low dose group (LSG): the course for the treatment of is the same, Folium Ilicis saponin D administration concentration is 30mg/kg/d.
(4) dosage group (MSG) in Folium Ilicis saponin D: the course for the treatment of is the same, and Folium Ilicis saponin D administration concentration is 75mg/kg/d.
(5) Folium Ilicis saponin D high dose group (HSG): the course for the treatment of is the same, Folium Ilicis saponin D administration concentration is 150mg/kg/d.
3, plasma biochemical index measures
(1) plasma TC (T-CHOL) level determination
Get 96 hole ELISA Plate, add each 2 μ l of different plasma sample, and the parallel each 2 μ l of variable concentrations TC titer adding standard substance doubling dilution and obtain, every hole adds 200 μ l working solutions again, after 37C hatches 10min, microplate reader is adopted to measure 490nm wavelength place absorbance value.TC concentration of standard solution is carried out linear fit with corresponding OD value, and OD value calculates the concentration of plasma TC per sample.
(2) blood plasma HDL-C (HDL-C) level determination
20% Polyethylene Glycol (PEG) is prepared: take PEG (MW8000) 20g, dissolve, finally supply volume to 100ml with the 0.2M glycine buffer of 60mlpH10.0.Get 50 μ l blood plasma to add in 1.5mlEp pipe, then add equal-volume 20%PEG, eddy blending machine mixes 90sec, 37 DEG C of shaking table 200rpm/min vibration 15min, 8000rpm × 10min.Be the lipoprotein being rich in apoB in precipitation, supernatant proceeded in another EP pipe, adopt the cholesterol concentration in said method detection supernatant.Note: because sample 20%PEG dilutes one times, 2 times of final tested volume are the actual concentrations of the HDL-C of plasma sample.
(3) plasma TG (triglyceride) level determination
Get 96 hole ELISA Plate, add each 2 μ l of different plasma sample, and the parallel each 2 μ l of variable concentrations TG titer adding standard substance doubling dilution and obtain, every hole adds 200 μ l working solutions again, 37 DEG C hatch 10min after, adopt microplate reader to measure 490nm wavelength place absorbance value.TG concentration of standard solution is carried out linear fit with corresponding OD value, and OD value calculates the concentration of plasma TG per sample.
(4) Lipoperoxide (MDA) measures
50 μ L dehydrated alcohol mix, with the dehydrated alcohol of equivalent for blank, with the standard substance of equivalent 10nmol/mL for standard pipe with 50 μ L sample blood plasma.After spiral mixing, 95 DEG C of water-bath 80min.Flowing water cooling after taking out, 8000rpm × 10min, the centrifugal precipitation that makes is complete.Get supernatant 800 μ L, 532nm place, 1cm optical path, distilled water returns to zero, and measures each pipe absorbance.
4, animal surgery operation
(1) anaesthetize
10% chloral hydrate anesthesia, by 10 μ l/g dosage lumbar injections.
(2) mice plasma is gathered
Mice fasting 6h, through mouse orbit posterior vein blood sampling about 200 μ l, anticoagulant heparin, 4 DEG C of centrifugal 4000rpm10min, get upper plasma, and after subpackage, frozen Yu – 80 DEG C is for subsequent use.
(3) cardiac perfusion
Along chest center line, mouse skin is cut off, with tweezers, skin is separated with subcutaneous tissue.Make a kerf in midline, along center line, rib is cut off, expose thoracic cavity and heart.A kerf is cut at position, mice right auricle, then rapid in apex of the heart position insertion syringe needle, slowly at the uniform velocity inject 20ml0.01MPBS and start heart perfusion, complete in 5min.
(4) draw materials
Mice is cut skin and subcutaneous thin film along ventrimeson, exposes each organs such as lung, liver, stomach, intestinal, spleen, pancreas, kidney.Get the tissues such as the liver of suitable size, kidney as required, freeze immediately after drawing materials in liquid nitrogen, turn frozen in-80 DEG C after a while.Sample is mainly used in extraction of lipid, and RNA extracts.Get the tissue leaving and taking morphological observation in addition, peel off aorta and heart, use 4% paraformaldehyde to fix, after 2h, proceed to 20% sucrose.Heart tissue is taken out with OCT embedding, after liquid nitrogen cools fixing 30s fast, and-20 DEG C of preservations.Partial liver tissue prepares paraffin section after dehydration, fixing, paraffin embedding, dyes for HE.4% paraformaldehyde 0.01MPBS prepares, and 65 DEG C of constant temperature stir and spend the night to dissolving completely, for subsequent use after filtering.
5, frozen section and section oil red O stain
After heart is separated with aorta, 4% paraformaldehyde extenal fixation 15min, OCT embed, after liquid nitrogen fixes 30s, and-80 DEG C of preservations.Naturally dry up after frozen section.4% paraformaldehyde fixes 10min.60% isopropyl alcohol 5min; ORO (distilled water and 0.5% stock solution (isopropyl alcohol is prepared) dilute by 4: 6 volume ratios, use front filtration, use in 1 ~ 2h) dyeing 30min; 60% isopropyl alcohol 2 times; Distillation washing 2 times; Haematoxylin redyeing 1 ~ 3min; Distillation washing 2 times; 90% glycerol mounting, to take pictures.Liver oil red O stain.
6, lipid analysis
Feces extraction of lipid: collect stool in mice weekly in experimentation, 60 DEG C of oven dry.Mix before extraction of lipid, after grinding, add chloroform: methanol (2: 1, v/v) carries out extraction of lipid twice, after organic facies nitrogen dries up, be dissolved in the TritonX-100 solution of 5%.
7, cell RNA extracts (with reference to Trizol description)
Cultivate in 12 orifice plates and after stimulating THP-1 cell differentiation, abandon culture medium, add 1mL1 × PBS and wash cell once, discard.Every hole adds 500 μ LTrizol and is placed in centrifuge tube, 12,000rpm centrifugal 10min under 4 DEG C of conditions.Get supernatant room temperature and leave standstill 5min.Add 100 μ L chloroforms, mixing 15s, room temperature leaves standstill 2 ~ 3min, 12,000rpm centrifugal 15min under 4 DEG C of conditions.Get supernatant and add 250 μ L isopropyl alcohols, room temperature leaves standstill 10min.12,000rpm centrifugal 10min under 4 DEG C of conditions.Abandon supernatant, add 75% ethanol 1mL washing precipitation.7,500rpm centrifugal 5min, vacuum drying RNA under 4 DEG C of conditions.With 0.1%DEPC water 20 μ L dissolve RNA, after subpackage-80 DEG C frozen.
8, reverse transcription
In 20 μ L reaction systems, add RNA5 μ g, random primer (50ng/ μ L) 2 μ L, 10mMdNTPmix2 μ L, supplement DEPC-treated distilled water to 20 μ L, fully mix, hatch ice bath 1min after 5min for 65 DEG C.10 × RTbuffer2.5 μ L is added, 0.1MDTT1 μ L, Rnaseout1 μ L, SuperScript in system
tMrT1 μ L, mixing; 42 DEG C hatch 60min after 70 DEG C hatch 15min.Ice bath cessation reaction, of short duration centrifugal after add RnaseH1 μ L, mixing, hatch 20min for 37 DEG C.Store or carry out PCR for-20 DEG C.
9, PCR in real time
Containing 10 × buffer2.5 μ L, 25mMMgCl in 25 μ L reaction systems
21.5 μ L, 10mMdNTP0.625 μ L, 10 μMs of P10.5 μ L, 10 μMs of P20.5 μ L, RTproduct1.0 μ L, Taqpolymerase0.25 μ L, SYBRgreen0.8uL, adds dH
2o is to 25 μ L cumulative volumes.RT product is substituted for negative control with distilled water.Reaction condition is 94 DEG C of degeneration 5min, 56 DEG C of annealing 30s, and 72 DEG C extend 1min; 94 DEG C of degeneration 30s afterwards, 56 DEG C of annealing 30s, 72 DEG C extend 1min, circulates after 30 times, 72 DEG C of extension 10min.
10, electrophoresis and data calculate
Get 10 μ LPCR products, 1.5% agarose gel (EB final concentration 0.5 μ g/mL) electrophoresis, ultraviolet imagery system is taken pictures.Mrna expression level is revised according to the cycle threshold (CT) of GAPDH in real-timePCR, and formula is 2 Δs
cT(Δ CT=GAPDHCT-geneofinterestCT).
11, intestinal tissue SABC
Section nature dries up.4% paraformaldehyde fixes 5-10min.0.01MPBS cleans 3 times.Methanol: H
2o
2(50: 1.5ml) soaks 10min.0.01MPBS cleans 3 times.5% rabbit anteserum is closed, 37 DEG C, 60min.Dry, directly add primary antibodie (Goat-anti-mouseACAT2,1: 100 dilution), 4 DEG C, spend the night.0.01MPBS cleans 3 times.Drip two anti-(Rabbit-anti-goat-HRP, 1: 400 dilutions), 37 DEG C, 60min.0.01MPBS cleans 3 times.DAB develops the color, and distilled water fully washs.Haematoxylin redyeing 1 ~ 3min.Distilled water fully washs.Graded series dehydration of alcohol: 70%, 80%, 95%, 95%, 100%, 100% each 2min.Transparent 10min × 2 of dimethylbenzene.Natural gum mounting.
12, statistical method
GraphpadPrism software is adopted to carry out, experimental data represents with average ± standard error (x ± SEM), between many groups, data compare employing one factor analysis of variance (one-wayANOVA), and between two groups of data, comparison in difference adopts Student ' st inspection.P<0.05 is that significant difference is remarkable.
(2) test and result
1, Folium Ilicis saponin D is on the impact of ApoE-/-mice plasma T-CHOL (TC) level
Each group after one week high lipid food feed, mice plasma T-CHOL is elevated to about 800mg/dL from 300-400mg/dL, starts gastric infusion after forming high hypercholesterolemia.Get weekly blood once afterwards, measure mice plasma total cholesterol level.Result shows, and all administration groups can reduce the plasma TC level of mice compared with high fat matched group.Middle and high dosage group and atorvastatin group are in administration plasma TC level reduction by 30% ~ 35% after a week, and wherein high dose group is substantially identical with atorvastatin group drug effect, there was no significant difference; Drug effect continues surrounding and keeps stable (Fig. 1).
2, Folium Ilicis saponin D is on the impact of the ApoE-/total triglyceride of-mice plasma (TG) level
After one week high cholesterol diet feeding, respectively organize plasma tg and all significantly raise, after forming high hypercholesterolemia, start gastric infusion for each group.Get weekly blood once afterwards, measure mice plasma triglyceride levels.Result shows, and all administration groups can reduce the plasma tg of mice compared with high fat matched group, significant difference (Fig. 2) compared with matched group.
3, Folium Ilicis saponin D is on the impact of ApoE-/-mice plasma high density lipoprotein (HDL-C) level
ApoE-/-mice is after giving high cholesterol diet, and each assembly does not exist significant difference.Get weekly blood once afterwards, measure mice plasma hdl level.Prompting Folium Ilicis saponin D does not affect (Fig. 3) ApoE-/-mice plasma high density lipoprotein (HDL-C) level.
4, Folium Ilicis saponin D is on ApoE-/-rat aorta is atherosis impact
After off-test, the aorta efferent tract speckle of each group of ApoE-/-mice is cut into slices, to dye and quantitatively.Aorta efferent tract, after frozen section, observes artery plaque form with HE dyeing, with oil red O (OilredO) to speckle dyeing (speckle is contaminated for redness), and quantitative to plaque area with software.Result of the test shows, and saponin KD and atorvastatin significantly can suppress the formation of aorta efferent tract atheromatous plaque, and the inhibition of atorvastatin and the middle and high dosage of KD significantly (P<0.01).Saponin KD reduces (Fig. 4, Fig. 5) with the increase plaque area of administration concentration.
5, Folium Ilicis saponin D is on the impact of total cholesterol level in ApoE-/-stool in mice
By the assay to T-CHOL in ApoE-/-stool in mice, detect KD to the impact of mice cholesterol intestinal absorption.Collect feces from the mice of fed high-fat diet, collect 2 days weekly, extract T-CHOL.Result shows, in each administration group, low dosage Ilex kudincha C. J. Tseng saponin group stool in mice cholesterol level is similar to high fat group, and middle and high dosage saponin group stool in mice cholesterol content ratio height fat matched group increase about 30%, with high fat group significant difference (Fig. 6).
6, Folium Ilicis saponin D is on the impact of ApoE-/-mouse small intestine tissue gene expression
In view of Folium Ilicis saponin D can increase the intestinal excretion of cholesterol, therefore the mrna expression level of this experiment to cholesterol intestinal absorption related gene detects.Detect the key enzyme NPC1L1 that gene comprises cholesterol intestinal absorption, ACAT2, ABCG5, ABCG8 and MTP etc.Result shows, and KD can significantly improve the mRNA level in-site of small intestine ABCG8, reduces the mRNA level in-site (Fig. 7) of ACAT2.ABCG5 and ABCG8 is the gene of involved in plant sterin and the cholesterol absorption be in recent years found, in small intestinal and liver, have high expressed, belongs to ABC transmembrane transport body family.Result display ABCG5 and ABCG8 can reduce the absorption of small intestinal to cholesterol after expressing and increasing, optionally increase the increase cholesterol biosynthesis of Neutral sterols excretion and compensatory, block this obviously to increase the response for dietary cholesterol content of blood plasma after gene and liver cholesterol levels, show that they play an important role in the bile secretion participating in food sterol absorption and sterin.ACAT catalysis free cholesterol and long-chain fatty acid form cholesteryl ester, and be the enzyme of synthetic cholesterol ester unique in cell, the expression of KD on ACAT1 does not affect, but significantly suppress the expression of ACAT2, thus suppress body to the esterification of cholesterol and absorption.Therefore KD is by suppressing the intestinal absorption of the expression inhibiting cholesterol of ACAT2, is promoted the excretion of cholesterol, thus effectively reduce the blood lipid level of ApoE-/-mice by the expression improving ABCG8.
7, Folium Ilicis saponin D is on the impact of ApoE-/-mice intestinal tissue
In order to verify the impact of Folium Ilicis saponin D on enterocyte ACAT2 protein expression.This test adopts the method for SABC, detects (Fig. 8) the ApoE-/-mice intestinal tissue ACAT2 protein expression of interior animal experiment.Result shows, and come to the same thing with test cell line, high fat matched group has a large amount of brown particle in ApoE-/-mouse small intestine organization edge, and D high dose administration group brown particle reduces in a large number.Show that D significantly suppress the ACAT2 expression of mouse small intestine, thus suppress mice to the esterification of cholesterol and Absorption.
Claims (4)
1. Folium Ilicis saponin D is for the preparation of the purposes prevented and/or treated in the medicine of dyslipidemia associated diseases and/or disease, described disease and/or disease be selected from hypercholesterolemia, hypertriglyceridemia, atherosclerosis, the injury of kidney that caused by hyperlipemia one or more, wherein said medicine is the medicine suppressing ACAT2 to express and/or improve ABCG8 to express.
2. purposes according to claim 1, is characterized in that, described disease and/or disease be selected from hypertriglyceridemia, hypercholesterolemia and atherosclerosis one or more.
3. Folium Ilicis saponin D is being expressed for the preparation of suppression ACAT2 and/or is improving the purposes in the medicine of ABCG8 expression.
4. purposes according to claim 3, is characterized in that, the intestinal absorption of described medicine by suppressing the expression of ACAT2 to suppress cholesterol, and/or is promoted the excretion of cholesterol by the expression improving ABCG8.
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