CN114085257B - Para-benzofurancaprolactam and two phenylpropanoid glycosides, preparation and use thereof - Google Patents
Para-benzofurancaprolactam and two phenylpropanoid glycosides, preparation and use thereof Download PDFInfo
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- 229930182470 glycoside Natural products 0.000 title abstract description 7
- 229930015704 phenylpropanoid Natural products 0.000 title abstract description 7
- -1 phenylpropanoid glycosides Chemical class 0.000 title abstract description 7
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- 244000022198 Mirabilis jalapa Species 0.000 claims abstract description 10
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- TYBDOHPQDOTAGR-UHFFFAOYSA-N pyrido[3,4-b]indol-9-ylmethanol Chemical compound C1=NC=C2N(CO)C3=CC=CC=C3C2=C1 TYBDOHPQDOTAGR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
- C07H1/08—Separation; Purification from natural products
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
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- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a pair of benzofurancaprolactam and two phenylpropanoid glycosides, preparation and application thereof, wherein the benzofurancaprolactam and the two phenylpropanoid glycosides have the activity of inhibiting the generation of IL-6, TNF-alpha and NO through the extraction and separation of Mirabilis jalapa, the chemical composition research of a system and the evaluation of the inhibition activity of inflammatory mediators.
Description
Technical Field
The invention belongs to the technical field of medicines, and in particular relates to benzofuran-caprolactam (1, 1a and 1 b) and phenylpropanoid glycoside (2, 3) in Tibetan medicine Mirabilis himalaica as well as a preparation method and application thereof.
Background
The Tibetan medicine Mirabilis jalapa is one of important Tibetan medicines for warming kidney, detumescence and relieving pain, and is received in the medicine standard of the Ministry of health of the people's republic of China. The Tibetan translation name is "Bazhu", the dry root of Mirabilis jalapa of Mirabilidaceae, which is produced in Qinghai-Tibet plateau, is mainly used as a medicament, and is regarded as the top grade in five roots by Tibetan medicine, and has the effects of warming kidney, promoting granulation, promoting urination, removing urinary calculus and drying "yellow water", and is commonly used for treating stomach cold, kidney cold, lower body cold, impotence edema, vesical calculus, lumbago, arthralgia and "yellow water" pain diseases.
Inflammation is the process by which human tissue produces a self-protective response when foreign pathogens and noxious stimuli invade the human body, involving the local vascular system and the immune system, as well as damaging various molecular mediators in the tissue. Uncontrolled inflammation, however, may lead to a range of diseases. Pulmonary fibrosis is the direct result of repeated damage to lung epithelial cells and myofibroblast activation, and this change is caused by persistent uncontrolled inflammation. Idiopathic pulmonary fibrosis is a chronic, highly lethal pulmonary interstitial disease caused by a variety of causes, and currently lacks effective therapeutic agents, and lung transplantation is the only therapeutic means that can prolong the life of patients. Thus, controlling the cascade activation of inflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor (TNF- α) and Nitric Oxide (NO) is a promising approach to treat inflammatory diseases as well as pulmonary fibrosis.
Disclosure of Invention
The invention provides a preparation method and application of benzofurancaprolactam and phenylpropanoid glycoside, which solve the problem that medicines for treating inflammatory diseases in the prior art can be selected less.
The technical scheme of the invention is as follows:
a compound of the structure:
the preparation method of the compound comprises the following steps:
(1) Pulverizing Mirabilis jalapa, extracting with solvent, and recovering extractive solution to obtain total extract;
(2) Dispersing the total extract obtained in the step (1) in water, extracting by adopting an organic solvent which is not miscible with water, and recovering the solvent to obtain an extract;
(3) Separating the raffinate (water phase) obtained in the step (2) by D101, MCI gel CHP-20P, HPLCone or medium pressure liquid chromatography, and performing gradient or isocratic elution by taking methanol/water or ethanol/water mixed solvent as mobile phase;
(4) And (3) separating the flow obtained in the step (3) by a preparative high performance liquid chromatography, and performing gradient elution by taking methanol/water or acetonitrile/water as a mobile phase to obtain the compound 1-3.
(5) And (3) performing chiral separation on the compound 1 obtained in the step (4) through high performance liquid chromatography, and performing gradient elution by taking acetonitrile/water as a mobile phase to obtain compounds 1a and 1b.
The Tibetan medicine Mirabilis jalapa is dried root of Mirabilis jalapa (Oxybaphus himalaicus Edgew or Mirabilis himalaica (edge.) Hein.) of Mirabilis (Nyctaginaceae) plant, tibetan language translation name "Bacina".
The extraction method in the step (1) is heating reflux extraction, leaching, diacolation or ultrasonic extraction, the solvent is at least one of methanol, ethanol, methanol-water or ethanol-water with the concentration of more than 20 percent, and the weight-volume ratio of the medicinal materials to the solvent is 1:4-1:15.
The extraction method in the step (2) uses any one of petroleum ether, dichloromethane, chloroform, diethyl ether and ethyl acetate as the organic solvent, and the volume ratio of the aqueous solution to the organic solvent is 1:1-1:2.
In the step (3), the gradient or isocratic elution is carried out by a methanol/water or ethanol/water system of 10:90-100:0. Wherein the optimized ratio of the methanol/water system is 10:90-60:40, and the optimized ratio of the ethanol/water system is 40:60.
In the step (4), methanol/water or acetonitrile/water is eluted in a gradient way according to the volume ratio of 20:80-90:10, and the optimal ratio is 20:80-50:50.
In the step (5), acetonitrile/water is eluted in a gradient way according to the volume ratio of 10:90-80:20, and the optimal ratio is 10:90-30:70.
A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable adjuvant.
The application of the compound and the pharmaceutical composition in preparing anti-inflammatory and anti-pulmonary fibrosis disease medicines.
The anti-inflammatory drug is a drug which inhibits the activity of IL-6, TNF-alpha and NO production.
The invention has the beneficial effects that: through systematic chemical composition research and inflammation medium inhibition activity evaluation of Tibetan medicine Mirabilis himalaica, the research discovers that the pair of novel benzofurancaprolactam and two phenylpropanoid glycosides provided by the invention have the activity of inhibiting the generation of IL-6, TNF-alpha and NO, and can be used for preparing medicines for treating inflammation and lung fibrosis related to the inflammation.
Drawings
FIG. 1 UV spectrum of compound 1 of the present invention;
FIG. 2 IR spectrum of Compound 1 of the present invention;
FIG. 3 HRESIMS spectra of Compound 1 of the invention;
FIG. 4 is a 1H-NMR spectrum of Compound 1 of the present invention;
FIG. 5 13C-NMR spectrum of compound 1 of the present invention;
FIG. 6 DEPT-135NMR spectrum of compound 1 of the present invention;
FIG. 7 is a COSY spectrum of Compound 1 of the present invention;
FIG. 8 HSQC spectrum of Compound 1 of the present invention;
FIG. 9 HMBC spectra of Compound 1 of the present invention;
FIG. 10 UV spectrum of Compound 2 of the present invention;
FIG. 11 is an IR spectrum of Compound 2 of the present invention;
FIG. 12 HRESIMS spectra of Compound 2 of the invention;
FIG. 13 is a 1H-NMR spectrum of Compound 2 of the present invention;
FIG. 14 shows the 13C-NMR spectrum of Compound 2 of the present invention;
FIG. 15 DEPT-135NMR spectra of Compound 2 of the invention;
FIG. 16 COSY spectrum of Compound 2 of the present invention;
FIG. 17 HSQC spectrum of Compound 2 of the present invention;
FIG. 18 HMBC spectra of Compound 2 of the present invention;
FIG. 19 UV spectrum of Compound 3 of the present invention;
FIG. 20 IR spectrum of Compound 3 of the present invention;
FIG. 21 HRESIMS patterns of Compound 3 of the invention;
FIG. 22 shows the 1H-NMR spectrum of Compound 3 of the invention;
FIG. 23 13C-NMR spectrum of compound 3 of the present invention;
FIG. 24 DEPT-135NMR spectrum of Compound 3 of the invention;
FIG. 25 COSY spectrum of Compound 3 of the present invention;
FIG. 26 HSQC spectrum of Compound 3 of the present invention;
FIG. 27 HMBC spectra of Compound 3 of the present invention;
FIG. 28 experimental and calculated ECD spectra of Compound 1 of the present invention.
Detailed Description
The invention is further illustrated below in connection with specific examples, which are to be understood as being illustrative of the invention and not limiting the scope of the invention.
Example 1
(1) 9.0 kg of Tibetan medicine Himalayan mirabilis jalapa medicinal material is crushed, is leached with 95% ethanol for 2 times at room temperature, is soaked for 24 hours each time, is subjected to reflux extraction with 7 times of 95% ethanol for 2 times, is subjected to 4 hours each time, and is subjected to decompression and solvent recovery to obtain 95% ethanol extract; reflux-extracting the residue with 10 times of 50% ethanol for 2 times (each for 4 hr), and recovering solvent under reduced pressure to obtain 50% ethanol extract.
(2) Dispersing the 95% ethanol extract and the 50% ethanol extract obtained in the step (1) in 5 times of water to prepare suspension, extracting with ethyl acetate to remove impurities, and filtering the water phase to obtain raffinate (water phase);
(3) Separating the extract obtained in the step (2) by using a D101 macroporous adsorption resin column, and performing isocratic elution by using an ethanol/water (40:60) mixed solvent as a mobile phase;
(4) The ethanol/water (40:60) fraction obtained in the above step (3) was separated by preparative high performance liquid chromatography (reversed phase silica gel C18) and gradient elution was performed (45:55 to 60:40) using acetonitrile/water as mobile phase to obtain compound 1 (yield 0.0012%), 2 (yield 0.0015%), 3 (yield 0.0009%).
(5) The compound 1 obtained in the above step (4) was subjected to chiral separation by high performance liquid chromatography (Daicel chiral IG column), and gradient elution was performed using acetonitrile/water (20:80) as a mobile phase to obtain the compound 1a (yield 0.0004%) and the compound 1b (yield 0.0008%).
Example 2
(1) 2 kg of Tibetan medicine Mirabilis jalapa, crushing, soaking in 60% ethanol at room temperature for 8 hours, reflux-extracting for 3 times, reflux-extracting for 8L multiplied by 1 hour each time, and recovering solvent under reduced pressure to obtain 60% ethanol extract;
(2) Dispersing the 85% ethanol extract obtained in the step (1) in water to prepare suspension, extracting with ethyl acetate to remove impurities, and filtering the water phase to obtain raffinate (water phase);
(3) Separating the extract obtained in the step (2) by medium-pressure liquid chromatography (reversed phase silica gel C18), and performing gradient elution by taking acetonitrile/water mixed solvent as mobile phase (15:85-70:30);
(4) The acetonitrile/water (20:80-60:40) fraction obtained in the step (3) was separated by preparative high performance liquid chromatography (reversed phase silica gel C18), and the new compound 1 (yield 0.0009%), 2 (yield 0.0012%), 3 (yield 0.0007%) was obtained by gradient elution (20:80-80:20) with acetonitrile/water as mobile phase.
(5) Compound 1 obtained in the above step (4) was subjected to high performance liquid chromatography (Daicel chiral IG column) and eluted with a gradient of acetonitrile/water (22:78) as a mobile phase to give Compound 1a (yield 0.0002%) and Compound 1b (yield 0.0004%).
Example 3
(1) 1 kg of Tibetan medicine Mirabilis jalapa, crushing, soaking in 70% methanol at room temperature for 4 hours, then extracting with ultrasonic vibration (ultrasonic frequency: 40KHz, ultrasonic power: 500W) for 3 times, 4.5L×1 hour each time, and recovering solvent under reduced pressure to obtain 70% methanol extract;
(2) Dispersing 70% methanol extract obtained in the step (1) in water to prepare suspension, extracting with diethyl ether to remove impurities, and filtering the water phase to obtain raffinate (aqueous solution);
(3) Separating the raffinate (aqueous solution) obtained in the step (2) by medium-pressure liquid chromatography (reversed phase silica gel C18), and performing gradient elution by taking a methanol/water mixed solvent as a mobile phase (10:90-80:20);
(4) The methanol/water (25:75-85:15) fraction obtained in the step (3) was separated by preparative high performance liquid chromatography (reversed phase silica gel C18), and the new compound 1 (yield 0.0010%), 2 (yield 0.0011%), 3 (yield 0.0008%) was obtained by gradient elution (18:82-75:25) using acetonitrile/water as mobile phase.
(5) Compound 1 obtained in the above step (4) was subjected to high performance liquid chromatography (Daicel chiral IG column) and eluted with a gradient of acetonitrile/water (18:82) as a mobile phase to give Compound 1a (yield 0.0003%) and Compound 1b (yield 0.0006%).
Experimental example 1
The structure of the compounds 1 to 3 was identified based on their physicochemical properties and spectroscopic data (the spectroscopic analysis patterns of the compounds 1 to 3 are shown in FIGS. 1 to 28).
The compound trans-benzofuran caprolactam-2-phenyl-10,3'-dimethoxy-4' -O-beta- D The structural identification data of glucopyranoside (1) are as follows:
white feather needle crystal (20% CNCH) 3 -H 2 O)；1a:[α] 20 D +47.5(c 0.04,75％MeOH-H 2 O)；ECDλ max (Δε) 214.4(+23.05),227.5(-17.56)nm；1b:[α] 20 D -44.8(c 0.03,75％MeOH-H 2 O)；ECDλ max (Δε) 214.9(-10.45),227.2(+12.86)nm；UVλ max (logε)280(3.98)nm；IR(KBr)ν max 3587,3524,3442, 3326,2924,2853,1652,1628,1601,1512,1386,1283,1264,1220,1085,948,801,770,668,552, 450； 1 H NMR(DMSO-d 6 400 MHz) and 13 C NMR(DMSO-d 6 100 MHz) data are shown in table 1; HRESIMS m/z 526.1678[ M+Na ]] + ,calcd for C 25 H 29 NNaO 10 + ,526.1684. The corresponding spectrograms obtained by experimental determination are shown in figures 1-9. The absolute configuration of the pair of compounds was determined by comparing the experimentally determined ECD pattern with the ECD pattern of the enantiomer calculated using the TDDFT (time Density functional theory) method. The absolute configurations of compounds 1a and 1b were determined as 2S,3S and 2R,3R, ECD maps, respectively, see FIG. 28.
Compound 6-O-feruloyl-beta- D Structural identification data of-glucopyranosyl- (1→5) -arabitol (2) are as follows:
pale yellow powder (MeOH); [ alpha ]] 20 D -18.0(c 0.02,MeOH)；UVλ max (logε)219(4.71),240(4.57),300 (4.65),325(4.80)nm；IR(KBr)ν max 3588,3525,3442,3307,3197,2924,1710,1649,1630,1599, 1516,1453,1429,1395,1273,1250,1177,1124,1073,1031,937,875,843,921,812,769,760, 718,525,531； 1 H-NMR(MeOD-d 4 400 MHz) and 13 C NMR(MeOD-d 4 100 MHz) data are shown in table 2; HRESIMS m/z 489.1626[ M-H ]] - ,calcd for C 21 H 29 O 13 - ,489.1614. The corresponding spectrograms obtained by experimental determination are shown in figures 10-18.
Compound 6-O-feruloyl-beta- D Structural identification data of-glucopyranosyl- (1→6) -glucitol (3) are as follows:
pale yellow powder (MeOH); [ alpha ]] 20 D -14.0(c 0.03,MeOH)；UVλ max (logε)218(4.70),234(4.54),300 (4.48),325(4.63)nm；IR(KBr)ν max 3524,3306,3209,2925,1701,1652,1646,1629,1598,1516, 1456,1429,1388,1377,1273,1251,1177,1125,1063,1030,1000,990,936,874,853,844,822, 562,552,532； 1 H-NMR(MeOD-d 4 400 MHz) and 13 C-NMR(MeOD-d 4 100 MHz) data are shown in table 2; HRESIMS m/z 519.1733[ M-H ]] - ,calcd for C 22 H 31 O 14 - 519.1719 the corresponding spectra obtained by experimental determination are shown in FIGS. 19-27.
TABLE 1 Compound 1 1 H and 13 c NMR data (DMSO-d) 6 400MHz nuclear magnetic resonance apparatus
TABLE 2 Compounds 2 and 3 1 H and 13 c NMR data (DMSO-d) 6 400MHz nuclear magnetic resonance apparatus
Experimental example 2
Anti-inflammatory Activity test of novel Compounds 1-3
Lipopolysaccharide (LPS) is adopted to induce RAW264.7 mouse macrophages to generate NO, IL-6 and TNF-alpha models, and the anti-inflammatory activity of the RAW264.7 mouse macrophages is evaluated by detecting the expression level of three inflammatory mediators in RAW264.7 cells after the test compound is added, so that potential drugs for resisting inflammation and treating ischemic cardiovascular and cerebrovascular diseases are discovered.
1. Method for preparing test compound solution
Test compounds were dissolved in DMSO to give a stock solution at a concentration of 50mM and stored at-20 ℃. The samples were diluted to 10mM, 5mM, 3mM, 1mM, 0.1mM and 0.01mM in the DMEM medium.
2. Culture of mouse RAW264.7 macrophages
The DMEM culture medium is used as a base to prepare a cell culture solution containing 10% of fetal bovine serum and 1% of double antibody (penicillin: streptomycin=1:1), wherein the temperature is 37 ℃ and the CO is 5% 2 Culturing in an incubator, changing the liquid once for 2-3 days until the cells are fully paved on the bottom of a culture bottle for testing.
3. Cytotoxicity of test compounds
Regulating cell density of logarithmic phase to 1×10 5 Inoculating into 96-well plate at 37deg.C with 5% CO 2 In the incubator, test compounds were added at different concentrations after 24 hours of incubation, and after 20 hours, the survival of the cells was observed and the toxicity of the compounds to the cells was quantitatively measured using MTT to determine the test concentration of the test compounds.
NO inhibition Activity assay
RAW264.7 cells in logarithmic phase were seeded in 96-well plates (1X 10) 4 And/well), for 24 hours, after the cells are completely attached, the compounds to be treated are added in different concentrations, after pretreatment for 30 minutes, LPS is added to a final concentration of 1.0 mug/mL, and the culture is continued for 24 hours. Taking 160 mu L of cell culture supernatant, adding 80 mu L of Griess reagent, measuring absorbance at 550nm according to Griess method, and determining absorbance value and standard curveThe inhibition of NO by each compound was calculated.
IL-6 and TNF-alpha inhibition Activity assay
RAW264.7 cells in the logarithmic growth phase were seeded in 96-well plates (1X 10) 5 Individual/well), for 24 hours, after the cells have been completely adherent, the compounds to be treated are added in different concentrations, after a pretreatment of 30 minutes, LPS is added to a final concentration of 10ng/mL, and the culture is continued for 24 hours. The extracted RNA was reverse transcribed into cDNA using ELISA kit for measuring IL-6 and TNF-alpha, and mRNA expression level of IL-6 and TNF-alpha was detected by real-time quantitative PCR method to determine inhibition of LPS-induced inflammatory response by each compound.
6. Statistical method
All data were processed and analyzed using the IBM SPSS Statistics statistical software package. Results are expressed as standard error of the mean. Calculating IC of each compound by using nonlinear regression fit of parameters such as each dose and inhibition rate 50 Values.
TABLE 3 Compounds 1-3 IC inhibiting NO production and IL-6, TNF-alpha secretion 50 Value (mu M)
a Dexamethasone (dexamethasone) was used as a positive control drug.
The data in Table 3 show that compounds 1-3 can obviously inhibit the generation of NO and/or the expression level of IL-6, TNF-alpha mRNA in Lipopolysaccharide (LSP) -induced mouse macrophage RAW264.7, and are in dose-dependent relationship, so that the compounds have obvious anti-inflammatory activity and can be used for preparing novel anti-inflammatory active medicaments.
The invention is not limited to the embodiments described above, and many variations of detail are possible without thereby departing from the scope and spirit of the invention.
Claims (6)
1. A compound of the structure:
2. a process for the preparation of a compound according to claim 1, comprising the steps of:
(1) Pulverizing Mirabilis jalapa, extracting with solvent, and recovering extractive solution to obtain total extract;
(2) Dispersing the total extract obtained in the step (1) in water, extracting by adopting an organic solvent which is not miscible with water, and separating and removing the extractant to obtain raffinate, namely a water phase;
(3) Separating the raffinate obtained in the step (2) by D101/MCI gel CHP-20P/HPLCone or reversed-phase medium-pressure liquid chromatography, and performing gradient or isocratic elution by taking methanol/water or ethanol/water mixed solvent as mobile phase;
(4) Separating the flow obtained in the step (3) by a preparative high performance liquid chromatography, and performing gradient elution by taking acetonitrile/water as a mobile phase to obtain compounds 1-3;
the solvent used in the step (1) is at least one of methanol and ethanol, and the weight-volume ratio of the medicinal materials to the solvent is 1:4-1:15;
the organic solvent in the step (2) is any one of diethyl ether and ethyl acetate, and the volume ratio of the aqueous solution to the organic solvent is 1:1-1:2;
in the step (3), the gradient or isocratic elution is carried out by a methanol/water or ethanol/water system of 10:90-100:0;
and (3) in the step (4), acetonitrile/water is eluted in a gradient way according to the volume ratio of 20:80-90:10.
3. The method for preparing a compound according to claim 2, wherein the extraction method in step (1) is a heat reflux extraction, a leaching, a percolation or an ultrasonic extraction.
4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable adjuvant.
5. Use of a compound according to claim 1, a pharmaceutical composition according to claim 4 for the preparation of a medicament for the treatment of inflammation and inflammation-associated pulmonary fibrosis.
6. The use according to claim 5, wherein the medicament for treating inflammation and inflammation-associated pulmonary fibrosis is a medicament having an activity of inhibiting IL-6, TNF- α and NO production.
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| CN110229128A (en) * | 2018-03-06 | 2019-09-13 | 蔡德成 | A kind of new benzofuran type compound and its extracting method |
| CN110669034A (en) * | 2019-09-30 | 2020-01-10 | 天津大学 | Isoflavone-chalcone dimer and chalcone dimer, preparation method and application |
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| CN110229128A (en) * | 2018-03-06 | 2019-09-13 | 蔡德成 | A kind of new benzofuran type compound and its extracting method |
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