CN118084855A - Aryl naphthalene phenolic acid compound extracted from ephedra root and preparation method and application thereof - Google Patents
Aryl naphthalene phenolic acid compound extracted from ephedra root and preparation method and application thereof Download PDFInfo
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- -1 Aryl naphthalene phenolic acid compound Chemical class 0.000 title claims abstract description 18
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000000935 antidepressant agent Substances 0.000 claims abstract description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 108
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- 239000002253 acid Substances 0.000 claims description 36
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to an aryl naphthalene phenolic acid compound extracted from ephedra roots, a preparation method and application thereof, which can effectively develop new medicinal value of ephedra and realize application problems in preparing antidepressant active medicaments.
Description
1. Technical field
The invention relates to the field of medicines, in particular to an aryl naphthalene phenolic acid compound extracted from ephedra roots, and a preparation method and application thereof.
2. Background art
Depression is a mental disorder characterized by major clinical features of mood dysfunction, bradycardia, hypovolemia, impaired cognitive function, and social dysfunction. Depression has now become the primary factor in suicide, severely affecting the quality of life of humans. At present, the clinical study on the level of corticosterone is related to the severity of depression, the level of plasma corticosterone of depression patients is increased, the effect of anti-glucocorticoid treatment on major depression patients is obvious, and the level of plasma corticosterone is reduced after treatment. Sustained elevation of corticosterone levels in plasma and cerebrospinal fluid may play an important role in the development of depression. Therefore, the screening of the antidepressant activity of the compound is carried out by adopting a corticosterone-induced PC-12 cell injury model, and the search of the natural product with potential antidepressant activity is a technical problem which is urgently solved by pharmaceutical researchers.
The ephedra root is called as a dried root and rhizome of a plant of the genus Ephedra (Ephedra Tourn ex Linn.) of the family Ephedraceae (EPHEDRACEAE DUMORTIER), namely, ephedra sinica (EPHEDRA SINICA Stapf.) or Ephedra sinica (EPHEDRA INTERMEDIA SCHRENK ET C.A.Mey.), and is mainly distributed in Shanxi, sichuan and other places, is a traditional Chinese medicine, and is received in Chinese pharmacopoeia. It is originally found in Shennong Ben Cao Jing (Shennong's herbal medicine), and has the effects of treating apoplexy, typhoid headache, wen Nve, releasing sweat, eliminating pathogenic heat, relieving cough, and removing cold and heat, and breaking accumulation. Related researches show that the chemical components of ephedra root mainly comprise alkaloids, flavonoids, phenolic acids, polysaccharides and the like. However, the further research on ephedra root and stem is less at present, in order to fully utilize abundant ephedra resources in China, further develop new medicinal value of ephedra and search for new active ingredients of ephedra, the ephedra root is selected as a research object, but no disclosure report on how to extract the ephedra root phenolic acid components with antidepressant activity from ephedra root is found, namely, aryl naphthalene phenolic acid compound 1 (ephedra root phenolic acid B), compound 2 (ephedra root phenolic acid C) and compound 3 (ephedra root phenolic acid D) which have potential antidepressant activity are prepared from ephedra root.
3. Summary of the invention
Aiming at the situation, the invention aims to solve the defects of the prior art, and provides an aryl naphthalene phenolic acid compound extracted from ephedra roots, a preparation method and application thereof, which can effectively develop new medicinal value of ephedra and realize the application problem in preparing antidepressant active medicaments.
The technical scheme is that the aryl naphthalene phenolic acid compound extracted from ephedra root comprises a compound 1, a compound 2 and a compound 3, wherein molecular formulas of the aryl naphthalene phenolic acid compound are C 14H12O5、C13H11NO3 and C 13H10O4 respectively, and structural formulas of the aryl naphthalene phenolic acid compound are as follows:
The preparation method comprises the following steps:
1) Extracting dried root and rhizome of herba Ephedrae with 15 times of water for 2 times (each time for 2 hr), extracting with 95% ethanol for 2 times (each time for 1 kg) of herba Ephedrae root with 4L ethanol under reflux for 2 hr, concentrating the extractive solution under reduced pressure to obtain total extract, dispersing with water, dissolving, sequentially extracting with petroleum ether (5 times×7L), dichloromethane (10 times×10L), ethyl acetate (12 times×10L), and n-butanol (6 times×6L), and recovering solvent to obtain petroleum ether part, dichloromethane part, ethyl acetate part, and n-butanol part;
2) Separating the dichloromethane part obtained in the step 1) by silica gel column chromatography (100-200 meshes), wherein the ratio of sample mixing silica gel to blank silica gel is 1:7-8, and petroleum ether-ethyl acetate is used according to the volume ratio of 10: 1. 5: 1. 3: 1. 1:1 and methylene dichloride-methanol according to a volume ratio of 20:1, carrying out gradient elution to obtain 15 corresponding fractions M1-M15;
3) Separating the fraction M12 obtained in the step 2) by silica gel column chromatography (200-300 meshes), and mixing petroleum ether and ethyl acetate according to a volume ratio of 30: 1. 20: 1. 10: 1. 5:1 and methylene chloride-methanol according to a volume ratio of 30: 1. 20: 1. 10:1, carrying out gradient elution to obtain 6 corresponding fractions M12-1 to M12-6;
4) Concentrating the fraction M12-5 obtained in the step 3) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 8 components M12-5-1-M12-5-8;
5) Separating the fraction M12-5-4 obtained in the step 4) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: collecting the flow with water=47:53 and flow speed of 3ml/min and retention time t R =27-29 min, concentrating and drying to obtain compound ephedrinoic acid B;
6) Separating the fraction M14 obtained in the step 2) by silica gel column chromatography (200-300 meshes), and mixing with petroleum ether-ethyl acetate according to a volume ratio of 50: 1. 30: 1. 15: 1. 5: 1. 3:1, carrying out gradient elution to obtain 5 corresponding fractions M14-1 to M14-5;
7) Concentrating the fraction M14-2 obtained in the step 6) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 5 components M14-2-1-M14-2-5;
8) Separating the fraction M14-2-4 obtained in the step 7) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: collecting the flow with water=42:58 and flow speed of 3ml/min and retention time t R =52-54 min, concentrating and drying to obtain compound ephedrinoic acid C;
9) Concentrating the fraction M11 obtained in the step 2) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 50%, 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 9 components M11-1 to M11-8;
10 Separating the fraction M11-8 obtained in the step 9) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=60:40, flow rate 3ml/min, collecting the fraction with retention time t R =7-9 min, concentrating and drying to obtain compound ephedrinophenolic acid D.
The application of the phenolic acid compounds ephedra root phenolic acid B, ephedra root phenolic acid C and ephedra root phenolic acid D in preparing antidepressant drugs is provided.
The invention is identified as three aryl naphthalene phenolic acid compounds extracted from ephedra root, the preparation method is easy to operate, the guidance is strong, the product purity is high, the compound can be effectively used for preparing antidepressant active medicaments, the medicinal value of ephedra root is developed, and the economic and social benefits are huge.
4. Description of the drawings
FIG. 1 is a chemical structure diagram of ephedra root phenolic acid 1,2 and 3.
FIG. 2 is a graph showing the effect of compounds 1,2, 3 of the invention on cell viability in a corticosterone-induced PC-12 cell injury model, wherein x —±s,n＝4.## P <0.01vs CORT; * P <0.05, < P <0.01vs cor.
FIG. 3 shows the 1 H-NMR spectrum (in DMSO-d 6) of ephedrinophen acid B as a compound of the invention.
FIG. 4 is a 13 C-NMR spectrum (in DMSO-d 6) of ephedrinophen acid B as a compound of the invention.
FIG. 5 shows the DEPT 135 spectrum (in DMSO-d 6) of ephedra rhizophenolic acid B as a compound of the present invention.
FIG. 6 is a 1H-1 H COSY spectrum (in DMSO-d 6) of ephedra rhizophenolic acid B as a compound of the invention.
FIG. 7 is the HSQC spectrum (in DMSO-d 6) of ephedra rhizophenolic acid B as a compound of the present invention.
FIG. 8 is a HMBC spectrum (in DMSO-d 6) of ephedra rhizophenolic acid B as a compound of the present invention.
FIG. 9 is an HR-ESI-MS spectrum (in MeOH) of ephedra rhizophenolic acid B as a compound of the present invention.
FIG. 10 is an IR spectrum (in MeOH) of ephedrinophen acid B, a compound of the invention.
FIG. 11 is a UV spectrum of ephedrinophen acid B (in MeOH) which is a compound of the present invention.
FIG. 12 is a 1 H-NMR spectrum (in DMSO-d 6) of ephedrinophenolic acid C as a compound of the invention.
FIG. 13 is a 13 C-NMR spectrum (in DMSO-d 6) of ephedrinophenolic acid C as a compound of the invention.
FIG. 14 is a DEPT 135 spectrum (in DMSO-d 6) of ephedra rhizophenolic acid C as a compound of the present invention.
FIG. 15 is a 1H-1 H COSY spectrum (in DMSO-d 6) of ephedra rhizophenolic acid C as a compound of the invention.
FIG. 16 is the HSQC spectrum (in DMSO-d 6) of ephedra rhizophenolic acid C as a compound of the present invention.
FIG. 17 is a HMBC spectrum (in DMSO-d 6) of ephedra rhizophenolic acid C as a compound of the present invention.
FIG. 18 is an HR-ESI-MS spectrum (in MeOH) of ephedrinophenolic acid C, a compound of the present invention.
FIG. 19 is an IR spectrum (in MeOH) of ephedrinophenolic acid C, a compound of the invention.
FIG. 20 is a UV spectrum of ephedrinophenolic acid C (in MeOH) as a compound of the invention.
FIG. 21 is a 1 H-NMR spectrum (in CD3 OD) of ephedrinophen acid D, a compound of the invention.
FIG. 22 is a 13 C-NMR spectrum (in CD3 OD) of ephedrinophen acid D, a compound of the invention.
FIG. 23 is a DEPT 135 spectrum (in CD3 OD) of ephedrinophend acid D, a compound of the invention.
FIG. 24 is a 1H-1 H COSY spectrum (in CD3 OD) of ephedra rhizophenolic acid D, a compound of the invention.
FIG. 25 is the HSQC spectrum (in CD3 OD) of ephedrinophenic acid D, a compound of the invention.
FIG. 26 is a HMBC spectrum (in CD3 OD) of ephedrinophen acid D, a compound of the invention.
FIG. 27 is a HR-ESI-MS spectrum (in MeOH) of ephedrinophen acid D as a compound of the present invention.
FIG. 28 is an IR spectrum (in MeOH) of ephedrinophen acid D, a compound of the invention.
FIG. 29 is a UV spectrum of ephedrinophen acid D (in MeOH) of a compound of the invention.
5. Detailed description of the preferred embodiments
The following describes in further detail the embodiments of the present invention with reference to the drawings and examples.
Example 1
The invention, when embodied, comprises the steps of:
1) Extracting dried root and rhizome of herba Ephedrae with 15 times of water for 2 times (each time for 2 hr) by water decoction method, extracting the extracted root of herba Ephedrae with 95% ethanol for 2 times (each time for 2 hr) by 10L heating reflux device, adding 4L ethanol into 1kg root of herba Ephedrae, heating reflux for 2 hr, concentrating the extractive solution under reduced pressure to obtain total extract 10.0kg, dispersing with water, dissolving, sequentially extracting with petroleum ether (5 times×7L), dichloromethane (10 times×10L), ethyl acetate (12 times×10L), and n-butanol (6 times×6L), recovering solvent to obtain petroleum ether part (211.6 g), dichloromethane part (245.1 g), ethyl acetate part (335.5 g), and n-butanol part (62.5 g);
2) Separating the dichloromethane part (170.0 g) obtained in the step 1) from blank silica gel (2000 g) by silica gel column chromatography (100-200 meshes), and mixing the blank silica gel (270 g) with petroleum ether-ethyl acetate according to a volume ratio of 10: 1. 5: 1. 3: 1. 1:1 and methylene dichloride-methanol according to a volume ratio of 20:1, carrying out gradient elution to obtain 15 corresponding fractions M1-M15;
3) Separating the fraction M12 (13.31 g) obtained in the step 2) by silica gel column chromatography (200-300 meshes) and mixing petroleum ether and ethyl acetate according to the volume ratio of 30: 1. 20: 1. 10: 1. 5:1 and methylene chloride-methanol according to a volume ratio of 30: 1. 20: 1. 10:1, carrying out gradient elution to obtain 6 corresponding fractions M12-1 to M12-6;
4) Concentrating the fraction M12-5 (6.3 g) obtained in the step 3) under reduced pressure (about 20 ml), carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting the spray detection of anisaldehyde-concentrated sulfuric acid, and combining the same fraction once every 100ml to obtain 8 components M12-5-1-M12-5-8;
5) The fraction M12-5-4 (101.76 mg) obtained in step 4) was separated by semi-preparative HPLC, the upper specification model: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=47:53, the flow rate is 3ml/min, the fraction with retention time t R =28.4 min is collected, concentrated and dried to obtain the compound ephedrinophen acid B;
6) Separating the fraction M14 (10.23 g) obtained in the step 2) by silica gel column chromatography (200-300 meshes) and mixing the components with petroleum ether-ethyl acetate according to the volume ratio of 50: 1. 30: 1. 15: 1. 5: 1. 3:1, carrying out gradient elution to obtain 5 corresponding fractions M14-1 to M14-5;
7) Concentrating the fraction M14-2 (3.3 g) obtained in the step 6) under reduced pressure (about 20 ml), carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting the spray detection of anisaldehyde-concentrated sulfuric acid, and combining the same fraction once every 100ml to obtain 5 components M14-2-1-M14-2-5;
8) The fraction M14-2-4 (67.71 mg) obtained in step 7) was separated by semi-preparative HPLC, the upper specification model: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=42:58, the flow rate is 3ml/min, the fraction with retention time t R =53.3 min is collected, concentrated and dried to obtain the compound ephedrinoic acid C;
9) Concentrating the fraction M11 (4.8 g) obtained in the step 2) under reduced pressure (about 20 ml), carrying out MCI GEL CHP P column chromatography, eluting with 50%, 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the column volume, the flow rate is 3ml/min, adopting the spray detection of anisaldehyde-concentrated sulfuric acid, and combining the same fraction once every 100ml to obtain 9 components M11-1 to M11-8;
10 Separating the fraction M11-8 (78.46 mg) obtained in step 9) by semi-preparative HPLC, the upper specification model being: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=60:40, flow rate 3ml/min, collecting fraction with retention time t R =8.6 min, concentrating and drying to obtain compound ephedrinophenolic acid D.
The invention selects ephedra root as a research object, carries out systematic separation and identification on chemical components of the ephedra root, and separates 3 novel aryl naphthalene phenolic acid compounds from the ephedra root, namely ephedra root phenolic acid B-D, and adopts a corticosterone-induced PC-12 cell injury model to carry out compound activity screening, and the result shows that: the compounds 1-3 can obviously improve PC-12 cell injury induced by corticosterone, have potential antidepressant activity, and related test data are as follows:
Instrument and reagent
Bruker AVANCE III 500 Nuclear magnetic resonance apparatus (TMS internal standard) (Bruker), nicolet is 10Microscope Spectrometer (Thermo Scientific, USA) for infrared spectrum, bruker maxis HD mass spectrometer for high resolution mass spectrum, shimadzu UV-2401PC apparatus for ultraviolet spectrum, WATERS AIANCE series 2695 high performance liquid system for high performance liquid chromatography, 2998 type diode array detector, empower3 chromatography datse:Sup>A workstation, C50 type high pressure liquid chromatograph, UV200 type ultraviolet detector [ Saiko Rui (North) technology Co., td ], YMC-Pack ODS-A column (250X 10mm. D.S-5mm,12 mm) (YMC Co., td.), the rest comprises an N-1100 type rotary evaporator (Shanghai Ailang instruments Co., td.), an A-1000S type water flow air extractor (Shanghai Ailang instruments Co., td.), an N-1111 type chilled water circulation device (Shanghai Ailang instruments Co., td.), an FDU-2110 type freeze dryer (Shanghai Ailang instruments Co., td.), se:Sup>A DFZ-60508 type vacuum drying oven (Shanghai Yiheng scientific instruments Co., td.), an AB204-N millionth precision analytical balance (METTER TOEDO), se:Sup>A iMARK type enzyme-labeled instrument (American BIO-RAD), se:Sup>A carbon dioxide incubator (Shanghai STIK), and an ultrse:Sup>A clean bench (Sujing group).
Rat adrenal pheochromocytoma cell PC-12, purchased from Shanghai cell bank of China academy of sciences; corticosterone (Shanghai ala Ding Shenghua B2302817, china); fluoxetine (Med Chem Express company 251273, usa); CCK8 (GLPBIO company 43 in the united states); 5-HT 7 antibody (WUHANSANYING Biotechnology Co., ltd 00058665); tubulin antibody (GR 3398636-5); DAPI stain (GR 3445296-5, ABCAM, USA); column chromatography packing Diaion HP-20, MCI GEL CHP-20P (Mitsubishi chemical company of Japan), silica gel H (100-200 mesh) used for column chromatography is produced by Qingdao ocean chemical factory, chromatographic pure reagent site Tianjin four-friend fine chemical Co., ltd, and analytical pure reagent is produced by Beijing chemical factory and Tianjin third chemical reagent factory.
Goat anti-rabbit IgG H & L (Alexa)488 Pre-adsorbed secondary antibody (GR 3449096-1); goat anti-mouse IgG H & L (Alexa/>)594 Pre-adsorbed secondary antibody (GR 3413419-1, ABCAM Co., USA); RPMI1640 medium (Invitrogen corporation 2315381, USA); fetal bovine serum (south america ex cell Bio company 12a 218);
The ephedra root selected by the invention is purchased from the Bozhou medicinal material market in 2021 month 5, and is identified as dried root and rhizome of ephedra (EPHEDRA SINICA stapf.) belonging to the ephedra family by teaching of pharmaceutical college Dong Cheng, and plant specimens (NO. 20210517) are stored in a traditional Chinese medicine chemical extraction and separation laboratory of Henan traditional Chinese medicine university.
Two structure identification
Mahonate B white amorphous powder (CH 2Cl2), HR-ESI-MS gave excimer ion peak m/z 261.0757[ M+H ] + (Calcd. For 261.0751), molecular formula C14H12O5;UV(MeOH)λmax(logε):249(1.38),256(1.38),290(0.77)nm;IRνmax:3369,1639,1462,1255cm-1;1H NMR(DMSO-d6,500MHz) and 13C NMR(DMSO-d6, 125MHz data are shown in Table 1.
Mahonate C white amorphous powder (CH 2Cl2), HR-ESI-MS excimer ion peak m/z 230.0810[ M+H ] + (Calcd. For 230.0811), molecular formula C13H11NO3;UV(MeOH)λmax(logε):203(1.38),247(1.55),288(0.89)nm;IRνmax:3441,1679,1466,1241,1209cm-1;1H NMR(CD3OD,500MHz) and 13C NMR(CD3 OD,125 MHz) data are shown in Table 1.
Mahonate D white amorphous powder (CH 2Cl2), HR-ESI-MS excimer ion peak m/z 253.0460[ M+H ] + (Calcd. For 253.0471), molecular formulas C13H10O4;UV(MeOH)λmax(logε):210(0.87),244(1.25),251(1.24),285(0.55)nm;IRνmax:3405,1618,1574,1397,1241cm-1;1H NMR(CD3OD,500MHz) and 13C NMR(CD3 OD,125 MHz) data are shown in Table 1.
TABLE 1 NMR spectroscopic data of ephedrinophenolic acid B, C, D
b Recorded in DMSO-d6,c Recorded in CD3OD,d Recorded in CD3OD
Three-activity assay
PC-12 cells were placed in a 5% CO 2, 37℃incubator with 10% fetal bovine serum in RPMI1640 medium, cells of the optimal growth phase were selected, digested with 0.25% trypsin, after termination of digestion, with 10% fetal bovine serum in RPMI1640 to a cell concentration of 1X 10 4, seeded in 96 well plates with 100. Mu.L of cell suspension per well, placed in the incubator, and after cell attachment, the medium was changed to serum-free medium. After 24h starvation, PC-12 cells were divided into 6 groups: normal NC (control, RPMI1640 medium), model cor (model, corticosterone), positive control FXT (fluoxetine, 0.4 μmol·l -1), dosing (1-3, 2 μmol·l -1) experimental. After 24h incubation for each group of 6 duplicate wells, after replacement of fresh medium, 10 μl of CCK8 solution was added to each well, after incubation at 37 ℃ for 1.5 hours, absorbance OD was measured at 450nm with a microplate reader, and cell viability was calculated according to the following formula:
cell viability = (dosing OD value-blank OD value)/(normal control OD value-blank OD value) ×100%.
Results of four Activity
Cell viability in the corticosterone-induced PC-12 cell injury model was examined by using CCK8 method for compounds 1-3, and the results are shown in FIG. 2. The cell viability of the model group was significantly reduced (P < 0.05) compared to the normal control group; compared with the model group, the compound 1-3 can obviously improve the cell activity (P < 0.01), improve the damage of corticosterone to PC-12 cells, and show that the compound 1-3 has good antidepressant activity.
Five conclusions
According to the invention, 3 novel aryl naphthalene phenolic acid compounds are separated from ephedra root, identified as ephedra root phenolic acid B, C, D, and compound activity screening is carried out by adopting a corticosterone-induced PC-12 cell damage model, and the result shows that: the ephedra root phenolic acid B, C, D can obviously improve PC-12 cell injury induced by corticosterone, has potential antidepressant activity, can be effectively used for preparing antidepressant drugs, and has huge development prospect and huge economic and social benefits.
Claims (5)
1. The aryl naphthalene phenolic acid compound extracted from ephedra root is characterized by comprising a compound 1, a compound 2 and a compound 3, wherein molecular formulas of the compound are C 14H12O5、C13H11NO3 and C 13H10O4 respectively, and the structural formulas are as follows:
2. the method for preparing an arylnaphthalene-based phenolic acid compound extracted from ephedra root as claimed in claim 1, comprising the steps of:
1) Extracting dried root and rhizome of herba Ephedrae with 15 times of water for 2 hr each time, extracting the extracted root with 95% ethanol for 2 times with 10L heating reflux device, adding 4L ethanol to 1kg root of herba Ephedrae each time, heating reflux for 2 hr, concentrating the extractive solution under reduced pressure to obtain total extract, dispersing with water, dissolving, sequentially extracting with petroleum ether, dichloromethane, ethyl acetate, and n-butanol, and recovering solvent to obtain petroleum ether part, dichloromethane part, ethyl acetate part, and n-butanol part;
2) Separating the dichloromethane part obtained in the step 1) by silica gel column chromatography, wherein the ratio of sample mixing silica gel to blank silica gel is 1:7-8, and petroleum ether-ethyl acetate is used according to the volume ratio of 10: 1. 5: 1. 3: 1. 1:1 and methylene dichloride-methanol according to a volume ratio of 20:1, carrying out gradient elution to obtain 15 corresponding fractions M1-M15;
3) Separating the fraction M12 obtained in the step 2) by silica gel column chromatography, and mixing petroleum ether and ethyl acetate according to a volume ratio of 30: 1. 20: 1. 10: 1. 5:1 and methylene chloride-methanol according to a volume ratio of 30: 1. 20: 1. 10:1, carrying out gradient elution to obtain 6 corresponding fractions M12-1 to M12-6;
4) Concentrating the fraction M12-5 obtained in the step 3) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 8 components M12-5-1-M12-5-8;
5) Separating the fraction M12-5-4 obtained in the step 4) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: collecting the flow with water=47:53 and flow speed of 3ml/min and retention time t R =27-29 min, concentrating and drying to obtain compound 1 ephedra root phenolic acid B;
6) Separating the fraction M14 obtained in the step 2) by silica gel column chromatography, and mixing petroleum ether and ethyl acetate according to a volume ratio of 50: 1. 30: 1. 15: 1. 5: 1. 3:1, carrying out gradient elution to obtain 5 corresponding fractions M14-1 to M14-5;
7) Concentrating the fraction M14-2 obtained in the step 6) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 5 components M14-2-1-M14-2-5;
8) Separating the fraction M14-2-4 obtained in the step 7) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: collecting the flow with water=42:58 and flow speed of 3ml/min and retention time t R =52-54 min, concentrating and drying to obtain compound 2 ephedra root phenolic acid C;
9) Concentrating the fraction M11 obtained in the step 2) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 50%, 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 9 components M11-1 to M11-8;
10 Separating the fraction M11-8 obtained in the step 9) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=60:40, flow rate 3ml/min, collecting the fraction with retention time t R =7-9 min, concentrating and drying to obtain compound 3 ephedrinophenolic acid D.
3. The method for preparing an arylnaphthalene-based phenolic acid compound extracted from ephedra root as claimed in claim 2, comprising the steps of:
1) Extracting dried root and rhizome of herba Ephedrae with 15 times of water for 2 times (each for 2 hr) by water decoction method, extracting the extracted root of herba Ephedrae with 95% ethanol for 2 times (each for 2 hr) by 10L heating reflux device, adding 4L ethanol into 1kg root of herba Ephedrae, heating reflux for 2 hr, concentrating the extractive solution under reduced pressure to obtain total extract 10.0kg, dispersing with water, dissolving, sequentially extracting with petroleum ether for 5 times (each for 7L); extracting with dichloromethane for 10 times, 10L each time; extracting with ethyl acetate for 12 times, 10L each time; extracting n-butanol for 6 times, 6L each time; recovering solvent to obtain petroleum ether part, dichloromethane part, ethyl acetate part and n-butanol part;
2) Separating the dichloromethane part obtained in the step 1) by silica gel column chromatography, wherein 2000g of blank silica gel and 270g of sample-mixing silica gel are mixed, and petroleum ether-ethyl acetate is used according to the volume ratio of 10: 1. 5: 1. 3: 1. 1:1 and methylene dichloride-methanol according to a volume ratio of 20:1, carrying out gradient elution to obtain 15 corresponding fractions M1-M15;
3) Separating the fraction M12 obtained in the step 2) by silica gel column chromatography, and mixing petroleum ether and ethyl acetate according to a volume ratio of 30: 1. 20: 1. 10: 1. 5:1 and methylene chloride-methanol according to a volume ratio of 30: 1. 20: 1. 10:1, carrying out gradient elution to obtain 6 corresponding fractions M12-1 to M12-6;
4) Concentrating the fraction M12-5 obtained in the step 3) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 8 components M12-5-1-M12-5-8;
5) Separating the fraction M12-5-4 obtained in the step 4) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=47:53, flow rate 3ml/min, collecting fraction with retention time t R =28.4 min, concentrating and drying to obtain compound 1 ephedra root phenolic acid B;
6) Separating the fraction M14 obtained in the step 2) by silica gel column chromatography, and mixing petroleum ether and ethyl acetate according to a volume ratio of 50: 1. 30: 1. 15: 1. 5: 1. 3:1, carrying out gradient elution to obtain 5 corresponding fractions M14-1 to M14-5;
7) Concentrating the fraction M14-2 obtained in the step 6) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 5 components M14-2-1-M14-2-5;
8) Separating the fraction M14-2-4 obtained in the step 7) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=42:58, flow rate 3ml/min, collecting fraction with retention time t R =53.3 min, concentrating and drying to obtain compound 2 ephedra root phenolic acid C;
9) Concentrating the fraction M11 obtained in the step 2) under reduced pressure, carrying out MCI GEL CHP P column chromatography, eluting with 50%, 70%, 80%, 90% and 100% methanol in sequence, wherein the use amount of each eluting part is 10 times of the volume of the column, the flow rate is 3ml/min, adopting anisaldehyde-concentrated sulfuric acid spray detection, detecting once every 100ml, and combining the same fractions to obtain 9 components M11-1 to M11-8;
10 Separating the fraction M11-8 obtained in the step 9) by semi-preparative HPLC, wherein the specification and model are as follows: 250X 10mm, 5 μm particle size, 12nm pore size 5C 18 -MS-II chromatographic column, mobile phase methanol: water=60:40, flow rate 3ml/min, collecting fraction with retention time t R =8.6 min, concentrating and drying to obtain compound 3 ephedrinophenolic acid D.
4. The use of an arylnaphthalene phenolic acid compound extracted from ephedra root as claimed in claim 1 in the preparation of antidepressant drugs.
5. Use of an arylnaphthalene phenolic acid compound extracted by the extraction method of claim 2 or 3 in the preparation of antidepressant drugs.
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