CN110283156B - Novel hypolipidemic compound extracted from acanthopanax senticosus - Google Patents
Novel hypolipidemic compound extracted from acanthopanax senticosus Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
Abstract
The invention relates to a compound extracted and separated from acanthopanax senticosus. The compound has very obvious effect of reducing blood fat for a high-fat model rat, can reduce the level of triglyceride in the blood of a high-fat model animal, and also has good effects of reducing cholesterol and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol; at the same time, the compounds are less biologically toxic. Therefore, the compound of the present invention is suitable for use as a hypolipidemic agent.
Description
Technical Field
The invention relates to the field of medicines, in particular to a novel blood fat reducing compound extracted from acanthopanax senticosus and a preparation method thereof.
Background
Dyslipidemia is generally referred to as elevated plasma cholesterol (TC) and/or Triglycerides (TG), commonly known as hyperlipidemia. Hyperlipidemia is a main risk factor for atherosclerosis and is also an important factor for inducing cardiovascular and cerebrovascular diseases, and the serum content of TC, TG and low-density lipoprotein cholesterol (LDL-C) is increased, the content of high-density lipoprotein cholesterol (HDL-C) is reduced, so that the hyperlipidemia can cause intimal injury, the permeability is increased, and the deposition of lipid in the vascular endothelium is accelerated. When blood fat is increased, a large amount of oxygen free radicals are generated, lipid peroxidation is enhanced, a large amount of MDA is generated, SOD activity is reduced, and generation and development of atherosclerosis are promoted.
At present, the treatment of chronic diseases such as dyslipidemia, such as drug treatment and medical means (operation) plays little role. The prevention and treatment of dyslipidemia mainly adopts a mode of combining drug treatment with non-drug treatment. The first-line blood fat reducing medicaments which are commonly used clinically are statins, and the medicaments have the strongest effect of reducing TC, reducing TG and increasing HDL-C simultaneously, thereby effectively controlling blood fat. In addition, nicotinic acid and its derivatives, fibrates and the like are also available. However, the used medicines only can play a role in controlling blood fat, have more side effects and cannot fundamentally prevent and regulate blood fat. Therefore, regulating blood lipid by natural plant active ingredients to prevent diseases caused by hyperlipidemia has become a hot spot of current medical care research.
Acanthopanax senticosus (Latin's name: Eleutherococcus senticosus) is a plant used as both medicine and food, and is collected from the 1977 edition of Chinese pharmacopoeia, the root and rhizome of the plant can be used as medicines, and has the effects of tonifying qi, strengthening spleen, tonifying kidney, soothing nerves, promoting blood circulation and removing blood stasis, and the acanthopanax senticosus recorded in the compendium of materia medica can tonify the strength, replenish vital essence, improve eyesight and descend qi, tonify five strains and seven injuries, lighten body and resist aging after long-term taking, and is commonly used for treating spleen-kidney yang deficiency, body deficiency, debilitation, inappetence, soreness and pain of waist and knees, insomnia and dreamin. Modern medical research also shows that acanthopanax has various pharmacological actions and clinical applications of reducing blood sugar, reducing blood fat, resisting virus, resisting tumor, relieving pain, sterilizing and the like. CN102579532A, CN101584719A and the like research the function of the acanthopanax extract in reducing blood fat; the influence of the acanthopanax leaf saponin on the blood fat of experimental hyperlipidemic rats is researched by Liuhongyan, university of Bai-Yu-En medical science, 21 st No. 4, 341 plus 343 and the like.
The invention discovers a novel natural compound in the acanthopanax senticosus extract, and the compound has good hypolipidemic effect.
Disclosure of Invention
The invention overcomes the defects of the prior art and provides a novel natural hypolipidemic compound which is extracted from acanthopanax senticosus.
The invention is realized by the following technical scheme:
the structural formula of the novel natural hypolipidemic compound is shown as the formula I:
the compound shown in the formula I is named as (E) -2- (benzo [ d ] [1,3] dioxol-5-ylmethyl) -3- (3, 5-dimethoxystyryl) cyclopenten-2-one.
In another aspect, the invention provides a process for the preparation of said compounds.
In yet another aspect, the invention provides pharmaceutical compositions comprising said compounds.
In a further aspect, the invention provides the use of the compound in the manufacture of a medicament.
Advantageous effects
The compound shown in the formula I has very obvious blood fat reducing effect on a high-fat model rat, can reduce the level of triglyceride in the blood of a high-fat model animal, and also has good effects of reducing cholesterol and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol; at the same time, the compounds are less biologically toxic. Therefore, the compound shown in the formula I is suitable for being used as a hypolipidemic drug.
Detailed Description
While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art and are intended to be within the scope of the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned in this application are herein incorporated by reference.
Compound (I)
The invention provides a novel natural hypolipidemic compound, which has a structural formula shown as a formula I:
the compound shown in the formula I is named as (E) -2- (benzo [ d ] [1,3] dioxol-5-ylmethyl) -3- (3, 5-dimethoxystyryl) cyclopenten-2-one.
Preparation method
The invention also provides a preparation method of the compound shown in the formula I, which comprises the following steps:
(1) taking a dried acanthopanax (Eleutherococcus senticosus) medicinal material, crushing, adding 60-80% ethanol with the mass being 5-10 times of that of the dried acanthopanax senticosus medicinal material, heating, refluxing and extracting for 1-3 times, filtering for 2-4 hours each time, combining extracting solutions, and concentrating under reduced pressure to 1/5-1/10 of the initial volume of the extracting solution to obtain an acanthopanax senticosus ethanol extract;
(2) adding water with the volume 2-4 times of that of the ethanol extract of acanthopanax senticosus into the ethanol extract of acanthopanax senticosus to suspend, sequentially extracting with cyclohexane and ethyl acetate with the same volume, and decompressing and recovering solvents from each extract to obtain a cyclohexane part and an ethyl acetate part;
(3) separating the ethyl acetate part by using a silica gel column, sequentially carrying out gradient elution by using petroleum ether-methanol with different proportions, and combining the same fractions to obtain a crude fraction; separating the crude fraction with MCI column, gradient eluting with diethyl ether-methanol of different proportions, and mixing the same fractions to obtain the compound shown in formula I.
In one embodiment, the amount of ethanol used in the extraction in the step 1 is 6-8 times of the mass of the acanthopanax root medicinal material, and the concentration is 70-75%.
In one embodiment, the cyclohexane is used for extraction 2-4 times in the step 2, and the ethyl acetate is used for extraction 3-5 times.
In one embodiment, the ethyl acetate part is separated by using a silica gel column in the step 3, gradient elution is sequentially carried out by using petroleum ether-methanol with different ratios of 99: 1-50: 50(V/V), and the same fractions are combined to obtain 5 components of I-V; and separating the component V by using an MCI column, performing gradient elution by using diethyl ether and methanol in different proportions of 99: 1-80: 20(V/V) in sequence, merging the same fractions to obtain 6 components of V (1) -V (6), wherein the component V (4) is a compound shown in a formula I.
In one embodiment, the different ratios of petroleum ether-methanol in silica gel column separation are 99:1, 95:5, 90:10, 80:20, 70:30, 60:40, 50:50(v/v) petroleum ether-methanol.
In one embodiment, the different ratios of ether-methanol at the time of MCI column separation refer to 99:1, 95:5, 90:10, 85:15, 80:20, 70:30(v/v) ether-methanol.
Composition comprising a metal oxide and a metal oxide
The present invention relates to medicaments comprising a compound of formula I as pharmaceutically active ingredient, optionally together with one or more inert carriers and/or diluents.
The compounds of the present invention and the other active substances to be combined therewith may be formed together in one formulation, for example a tablet or capsule, or formulated separately in two identical or different formulations, for example so-called kits.
The compounds of the present invention may be administered to animals, preferably mammals including humans, as medicaments, on their own, in admixture with each other or in the form of pharmaceutical compositions. The administration mode can be as follows: oral administration, for example in the form of tablets, film-coated tablets, sugar-coated tablets, granules, hard and soft gelatin capsules, solutions (including water, alcohol and oily solutions), juices, drops, syrups, emulsions or suspensions; rectal administration, for example in the form of suppositories; or parenterally, for example in the form of solutions for subcutaneous, intramuscular or intravenous injection or infusion, in particular in the form of aqueous solutions.
Suitable pharmaceutical compounds for oral administration may be in the form of separate units, such as capsules, cachets, lozenges, or tablets, each containing a defined amount of a compound of the invention; is in the form of powder or granule; as a solution or suspension in an aqueous or non-aqueous liquid; or an oil-in-water or water-in-oil emulsion. As already mentioned, these compositions may be prepared by any suitable pharmaceutical process comprising a step in which the active ingredient and the carrier (which may consist of one or more other ingredients) are brought into contact. Compositions are generally prepared by uniformly and homogeneously mixing the active ingredient with liquid and/or finely divided solid carriers, after which the product is shaped, if desired. Thus, for example, a tablet may be prepared by compressing or molding a powder or granules of the compound, suitably together with one or more other ingredients. Compressed tablets may be prepared by tableting the compound in free-flowing form (e.g. powder or granules) in a suitable machine, if appropriate together with a binder, glidant, inert diluent and/or surfactant/dispersant(s). Molded tablets may be prepared by molding in a suitable machine the compound in powder form and which has been moistened with an inert liquid diluent.
Pharmaceutical compositions suitable for peroral (sublingual) administration include lozenges comprising a compound of the invention with a flavouring, usually sucrose and acacia or tragacanth, and pastilles comprising the compound in an inert base, such as gelatin and glycerol or sucrose and acacia.
Coated formulations and coated sustained release formulations, in particular acid-and gastric juice-resistant formulations, also belong within the framework of the present invention. Suitable coatings resistant to gastric juices include cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate and anionic polymers of methacrylic acid and methyl methacrylate.
Pharmaceutical compositions suitable for rectal administration are preferably in the form of single dose suppositories. These can be prepared as follows: the compounds of the present invention are mixed with one or more conventional solid carriers and the resulting mixture is shaped.
Pharmaceutical compositions suitable for parenteral administration preferably comprise sterile aqueous preparations of a compound of the invention, which are preferably isotonic with the blood of the intended recipient. Although intravenous administration of these formulations is preferred, subcutaneous, intramuscular or intradermal injection may also be administered. These formulations can preferably be prepared as follows: the compound is mixed with water and the resulting solution is rendered sterile and isotonic with blood. Injectable compositions of the invention will generally contain from 0.1% to 5% by weight of the active compound.
Other suitable administration forms are, for example, transdermal or topical administration, for example in the form of ointments, creams, tinctures, sprays, powders or transdermal therapeutic systems; or by inhalation, for example in the form of a nasal spray or aerosol mixture, or for example in the form of microcapsules, implants.
Pharmaceutical compositions suitable for topical use on the skin are preferably in the form of ointments, creams, lotions, pastes, sprays, aerosols or oils. The carrier used may be petroleum jelly, lanolin, polyethylene glycol, alcohol and a combination of two or more of these substances. The active ingredient is generally present at a concentration of 0.1% to 15% by weight of the composition, for example 0.5% to 2% by weight.
Transdermal administration is also possible. Pharmaceutical compositions suitable for transdermal administration may be in the form of a single patch suitable for long-term intimate contact with the epidermis of a patient. The above-mentioned patches suitably contain the active ingredient in an aqueous solution, which is suitably buffered, dissolved and/or dispersed in an adhesive or dispersed in a polymer. Suitable active ingredient concentrations are about 1% to 35%, preferably 3% to 15%. A particular choice is for the active ingredient to be released by electrotransport or iontophoresis.
The compounds of the invention can be used in a wide variety of combinations with other pharmacologically active compounds, either by separate administration of the active ingredients to the patient or in the form of a combination product in which a plurality of active ingredients are present in one pharmaceutical preparation. When administered separately, they may be administered simultaneously or sequentially in any order. The amounts of the compound of the present invention and the other pharmaceutically active ingredient(s) and the relative timing of administration can be selected to achieve the desired combined therapeutic effect. The administration of the combination may be accompanied by: (1) a unit pharmaceutical composition comprising all pharmaceutically active ingredients; or (2) separate pharmaceutical compositions each comprising at least one pharmaceutically active ingredient. Alternatively, the compositions may be administered separately, sequentially, wherein one therapeutic agent is administered prior to the second, and vice versa. The sequential administration may be close in time or remote in time.
Therapeutic agents suitable for combination include, for example, antidiabetics (such as insulin and insulin derivatives, gastrointestinal peptides, sodium-dependent glucose transporter 2(SGLT-2) inhibitors, biguanides, thiazolidinediones, GPR119 agonists and the like), anti-inflammatory agents for the treatment of metabolic syndrome and diabetes (such as nuclear factor kb inhibitors, adenosine monophosphate activated protein kinase), one or more other lipid lowering agents (such as simvastatin, rosuvastatin and the like), one or more active substances for the treatment of obesity (such as bromocriptine, phentermine and the like), agents affecting hypertension, chronic heart failure or atherosclerosis (such as nitric oxide donors, AT1 antagonists or angiotensin II (AT2) receptor antagonists) and the like.
The dosage of a compound of the invention to achieve a desired therapeutic effect will depend on a number of factors, such as the particular compound selected, the intended use, the mode of administration and the clinical condition of the patient. The daily dosage will generally be in the range 0.3mg to 100mg (preferably 3mg to 50mg) per day per kilogram body weight, for example 3-10 mg/kg/day. The compounds of the invention may be used as such, but they are preferably presented in the form of a pharmaceutical composition with a compatible carrier. Of course, the carrier must be acceptable in the sense of being compatible with the other ingredients of the composition and not injurious to the patient's health. The carrier may be a solid or a liquid or both and is preferably formulated with the compound as a single dose, e.g. a tablet, which may contain from 0.05% to 95% by weight of the active ingredient. The pharmaceutical compositions of the present invention may be prepared by one of the known pharmaceutical methods which generally comprise admixing the ingredients with pharmacologically acceptable carriers and/or excipients.
Use of
The compound shown in the formula I has good effects of reducing triglyceride level, cholesterol and low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol, and has low biological toxicity, so the compound is suitable for being used as a blood fat reducing medicine.
Therefore, the invention also provides the application of the compound shown in the formula I in preparing a medicament for reducing blood fat.
In another aspect, the invention also provides application of the compound shown in the formula I in preparing a medicament for preventing and/or treating cardiovascular and cerebrovascular diseases.
In one embodiment, the cardiovascular and cerebrovascular disease is hypertension, hyperlipidemia, and/or atherosclerosis.
Examples
Example 1: preparation of the Compound of formula I
(1) Taking 3Kg of dried acanthopanax root medicinal material, crushing, adding 24Kg of 75% ethanol, heating, refluxing and extracting for 3 times, each time for 4h, filtering, combining extracting solutions, and concentrating under reduced pressure to 1/5 of the initial volume of the extracting solution to obtain the acanthopanax root ethanol extract;
(2) suspending the ethanol extract of acanthopanax senticosus by adding 3 times of water, sequentially extracting with cyclohexane and ethyl acetate with equal volume, wherein the cyclohexane is extracted for 2 times, the ethyl acetate is extracted for 4 times, combining the extracts of the same solvent, and respectively recovering the solvent under reduced pressure to obtain a cyclohexane part (10.5g) and an ethyl acetate part (22.3 g);
(3) separating the ethyl acetate part with silica gel column, gradient eluting with petroleum ether-methanol of 99:1, 95:5, 90:10, 80:20, 70:30, 60:40, 50:50(V/V) in sequence, and mixing the same fractions to obtain 5 components of components I (1.8g), II (2.2g), III (3.7g), IV (0.9g), and V (2.5 g); and separating the component V by using an MCI column, performing gradient elution by using diethyl ether and methanol at the ratio of 99:1, 95:5, 90:10, 85:15, 80:20 and 70:30(V/V) in sequence, and combining the same fractions to obtain 6 components of V (1) (33.5mg), V (2) (28.4mg), V (3) (17.2mg), V (4) (24.6mg), V (5) (17.3mg) and V (6) (19.5mg), wherein the component V (4) is the target compound.
And (3) structural identification:
high resolution mass spectrometry results, HR-ESI-MS: m/z 401.1342[ M + Na ]]+(C23H22O5Na, calculated as 401.1365), the compound of formula I thus has the formula C23H22O5The unsaturation degree is 13. IR spectrum at 1675cm-1There is a stretching vibration peak attributed to C ═ O, combined to 1600cm-1A nearby stretching vibration peak attributed to C ═ C can be determined that a carbonyl-double bond conjugated structure exists in the molecular structure; at 1050cm-1-1010cm-1A stretching vibration peak attributed to C-O-C exists nearby, and indicates that ether bonds exist in the molecule.1H NMR(600MHz，CDCl3) The spectrum shows trans double bond hydrogen of delta 6.87d (15.2Hz), 6.81d (15.2 Hz); shows the benzene ring hydrogen peaks of delta 6.83s, 6.97d (7.5Hz), 6.93d (7.5Hz), 6.73s, 6.61s and 6.74 s; two methoxy hydrogens are shown for δ 3.80 s.13C NMR(600MHz，CDCl3) The spectrum shows the carbonyl carbon of delta 206.3, the double bond carbon of delta 148.5, 131.7, 134.8, 127.1, the benzene ring carbon of delta 131.0, 109.4, 147.1, 145.7, 108.6, 122.9, 136.8, 105.4, 161.2, 99.4, 161.2, 105.4, and the two methoxy carbons of delta 55.7. Process for the preparation of compounds of formula I1H NMR(600MHz，CDCl3) And13C NMR(600MHz，CDCl3) Summarized in table 1 below.
Table 1:
by analysis with reference to the respective characterization data, the structure of the compound of formula I can be determined as follows:
it is named as: (E) -2- (benzo [ d ] [1,3] dioxol-5-ylmethyl) -3- (3, 5-dimethoxystyryl) cyclopenten-2-one.
Example 2: test for hypolipidemic Activity of Compounds of formula I
Preparing a suspension liquid medicine of 10mg/ml of the compound shown in the formula I by using 5% DMSO, 2% Tween80 and 93% physiological saline, and ultrasonically mixing the suspension liquid medicine before use; each animal was given a dose of 20mg/kg at a dose volume of 200. mu.l/100 g.
The experimental method comprises the following steps: 36 SD rats, each half of male and female, were randomly divided into 3 groups, namely a normal control group, a model control group, and a compound group (i.e., administration group) represented by formula I, and 12 rats were each group. Feeding high-fat feed to the model control group and the administration group, and simultaneously performing intragastric administration on the compound shown in the formula I for 1 time (20mg/kg) every day for 4 weeks; the model control group was administered an equal volume of water by gavage. The normal control group was given normal feed. After 4 weeks and 1 hour after the last administration, rats were anesthetized by intraperitoneal injection of 45mg/kg of 1% pentobarbital (fasting does not prohibit water for 12 hours), blood was taken from the abdominal aorta, serum was separated, and the Total Cholesterol (TC), Triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) contents in the serum were measured. The statistical method comprises the following steps: statistical analysis was performed using Prism software. Comparing differences among the groups by ANOVA analysis; the two groups were compared using the t-test. The results are shown in table 1 below.
Table 1:
| test set | TC/mmol/l | TG/mmol/l | HDL-C/mmol/l | LDL-C/mmol/l |
| Normal control group | 1.38±0.21** | 1.49±0.18** | 1.19±0.22* | 0.42±0.08* |
| Model control group | 2.89±0.40 | 2.51±0.24 | 0.74±0.17 | 0.86±0.10 |
| Administration set | 2.02±0.33* | 1.78±0.19* | 0.93±0.20* | 0.57±0.06* |
Note: p < 0.05, P < 0.01, compared to model control
The experimental results are as follows: the content measurement results of TC, TG and HDL-C, LDL-C of the rats in the model control group are obviously inferior to those of the rats in the normal control group, which shows that the establishment of the hyperlipidemia rat model is successful after the rats are fed with high-fat feed. The content measurement results of TC, TG and HDL-C, LDL-C of rats in the administration group are superior to those of a model control group, and the compound shown in the formula I has a very obvious blood fat reducing effect on high-fat model rats.
Example 3: acute toxicity test
The experimental method comprises the following steps: taking 20 ICR mice with the weight of 18-20g, and taking the mice with the weight of half of the ICR mice; fasting was carried out for 16 hours before administration, and a single administration (5g/kg, 0.5% CMC-Na) was carried out by oral gavage, and fasting was carried out for 3 to 4 hours after administration of the test drug, and the general symptoms were closely observed for 6 hours and continued for 14 days. The experimental results are as follows: all animals did not die during the test, and there was no abnormality in the general condition.
Claims (10)
1. A compound of formula I:
2. a process for the preparation of a compound of formula I according to claim 1, comprising the steps of:
(1) taking a dried acanthopanax (Eleutherococcus senticosus) medicinal material, crushing, adding 60-80% ethanol with the mass being 5-10 times of that of the dried acanthopanax senticosus medicinal material, heating, refluxing and extracting for 1-3 times, filtering for 2-4 hours each time, combining extracting solutions, and concentrating under reduced pressure to 1/5-1/10 of the initial volume of the extracting solution to obtain an acanthopanax senticosus ethanol extract;
(2) adding water with the volume 2-4 times of that of the ethanol extract of acanthopanax senticosus into the ethanol extract of acanthopanax senticosus to suspend, sequentially extracting with cyclohexane and ethyl acetate with the same volume, and decompressing and recovering solvents from each extract to obtain a cyclohexane part and an ethyl acetate part;
(3) separating the ethyl acetate part by using a silica gel column, sequentially carrying out gradient elution by using petroleum ether-methanol with different proportions, and combining the same fractions to obtain a crude fraction; separating the crude fraction with MCI column, gradient eluting with diethyl ether-methanol of different proportions, and mixing the same fractions to obtain the compound shown in formula I.
3. The method according to claim 2, wherein the amount of ethanol used in the extraction in step 1 is 6-8 times of the mass of the acanthopanax root, and the concentration is 70-75%.
4. The method of claim 2, wherein the extraction in step 2 is performed 2-4 times with cyclohexane and 3-5 times with ethyl acetate.
5. The method according to claim 2, wherein the ethyl acetate fraction in step 3 is separated by silica gel column, gradient elution is sequentially carried out by petroleum ether-methanol with different ratios of 99: 1-50: 50(V/V), and the same fractions are combined to obtain 5 components of I-V; and separating the component V by using an MCI column, performing gradient elution by using diethyl ether and methanol in different proportions of 99: 1-80: 20(V/V) in sequence, merging the same fractions to obtain 6 components of V (1) -V (6), wherein the component V (4) is a compound shown in a formula I.
6. The method of claim 5, wherein the different ratios of petroleum ether-methanol in the silica gel column separation are 99:1, 95:5, 90:10, 80:20, 70:30, 60:40, 50:50(v/v) petroleum ether-methanol.
7. The method of claim 5, wherein the different ratios of ether-methanol in the MCI column separation are 99:1, 95:5, 90:10, 85:15, 80:20, and 70:30(v/v) ether-methanol.
8. A pharmaceutical composition comprising a compound of formula I according to claim 1 as pharmaceutically active ingredient, optionally comprising one or more inert carriers and/or diluents.
9. The use of a compound of formula I according to claim 1 for the preparation of a medicament for lowering blood lipids.
10. The use of a compound of formula I according to claim 1 for the preparation of a medicament for the prevention and/or treatment of cardiovascular and cerebrovascular diseases, which are hyperlipemia and/or atherosclerosis.
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