CN116589476A - Long-chain diterpene stellera chamaejasme A and preparation method and application thereof - Google Patents
Long-chain diterpene stellera chamaejasme A and preparation method and application thereof Download PDFInfo
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- 241001263604 Stellera chamaejasme Species 0.000 title claims abstract description 53
- 150000004141 diterpene derivatives Chemical class 0.000 title claims abstract description 45
- 229930004069 diterpene Natural products 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 201000007270 liver cancer Diseases 0.000 claims abstract description 23
- 208000014018 liver neoplasm Diseases 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 15
- 238000000926 separation method Methods 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 99
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000010828 elution Methods 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- 239000003480 eluent Substances 0.000 claims description 11
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 8
- 101710182532 Toxin a Proteins 0.000 claims description 7
- 101710084578 Short neurotoxin 1 Proteins 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 238000002791 soaking Methods 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 230000005764 inhibitory process Effects 0.000 abstract description 5
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 description 7
- 238000005457 optimization Methods 0.000 description 5
- 241001263603 Stellera Species 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- -1 Daphnane diterpene Chemical class 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000005918 in vitro anti-tumor Effects 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 241000221017 Euphorbiaceae Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000002276 neurotropic effect Effects 0.000 description 1
- 125000002092 orthoester group Chemical group 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/18—Bridged systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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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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Abstract
The invention relates to the technical field of separation and purification of radix euphorbiae Fischerianae, in particular to long-chain diterpene radix euphorbiae Fischerianae A, a preparation method thereof and application thereof in preparing medicaments for preventing liver cancer and resisting liver cancer. The invention discloses a compound long-chain diterpenoid stellera chamaejasme A for the first time, and the long-chain stellera chamaejasme A has a strong inhibition effect on HepG human liver cancer cells, so that the long-chain stellera chamaejasme A is applied as a potential anti-tumor drug.
Description
Technical Field
The invention relates to the technical field of separation and purification of radix euphorbiae Fischerianae, in particular to a long-chain diterpene radix euphorbiae Fischerianae A and a preparation method and application thereof.
Background
Liver cancer is a malignant tumor of liver, and can be divided into primary and secondary two kinds. Primary liver malignancy originates from the epithelial or mesenchymal tissue of the liver, the former being known as primary liver cancer, a severe malignancy; the latter is called sarcoma, which is less common than primary liver cancer. Secondary or metastatic liver cancer refers to invasion of malignant tumors of multiple organ origins throughout the body into the liver. Liver metastasis is commonly observed in malignant tumors of organs such as stomach, biliary tract, pancreas, colorectal, ovary, uterus, lung and breast. The treatment of liver cancer comprises various means such as operation, radiotherapy and chemotherapy, intervention, targeted drugs, immunotherapy and the like.
Daphnane diterpene natural products are mainly distributed in daphnaceae and Euphorbiaceae plants, have 5/7/6 tricyclic skeleton 1, usually have hydroxyl groups at the C3, C4, C5, C9, C13, C14, C20 positions, and have specific orthoester structures at the C9, C13, C14. To date, hundreds of daphnane diterpenoid natural products have been isolated and identified, which show good biological activity in terms of anti-HIV, anti-cancer, anti-leukemia, neurotropic, insecticidal and cytotoxic.
The stellera chamaejasme (stellera chamaejasme) is stellera plants of stellera chamaejasme of the daphnaceae, and is only distributed in Zhaosu county and foreign Ji-si-Tan areas of Xinjiang in China, and because of unique geographic environment and growing area, people have less research on the efficacy components of the stellera chamaejasme, and the main active component is daphne diterpenoid components, so that the stellera chamaejasme has multiple effects of resisting tumor, resisting inflammation and the like. Therefore, the diterpenoid monomer compound of the radix euphorbiae lathyris is developed and utilized, the potential medicinal value of the diterpenoid monomer compound is further excavated, and the diterpenoid monomer compound has remarkable significance for the deep development and utilization of the radix euphorbiae lathyris especially in the aspect of liver cancer immunotherapy.
Disclosure of Invention
The invention provides a long-chain diterpenoid stellera chamaejasme A, a preparation method and application thereof, overcomes the defects of the prior art, and firstly discloses the long-chain diterpenoid stellera chamaejasme A which can be applied to preparation of medicines for preventing and treating liver cancer and medicines for inhibiting or/and killing HepG human liver cancer cells.
One of the technical schemes of the invention is realized by the following measures: a long chain diterpene stellera chamaejasme A has a chemical structural formula of
。
The following are further optimizations and/or improvements to one of the above-described inventive solutions:
the long-chain diterpene stellera chamaejasme A is obtained by the following method: firstly, crushing radix euphorbiae lathyris, adding methanol, soaking for 3 to 4 hours at room temperature, heating and reflux-extracting for 3 times at 50 to 60 ℃ for 1 to 3 hours each time, combining the reflux extracting solutions each time, decompressing and recovering and concentrating to obtain radix euphorbiae lathyris extract; dispersing the radix euphorbiae lathyris extract into suspension by using water, sequentially extracting with dichloromethane and ethyl acetate, concentrating the extract to sequentially obtain dichloromethane part extract and ethyl acetate part extract; step three, taking the extract of the dichloromethane part, and performing gradient elution and separation by using a silica gel column to obtain 8 fractions, wherein the gradient eluent of the silica gel column comprises dichloromethane and methanol, and the volume ratio of the dichloromethane to the methanol is 100:1, 50:1, 30:1, 20:1, 10:1, 5:1, 3:1 and 1:1 in sequence; and fourthly, purifying and separating the 3 rd fraction in the 8 obtained fractions after high performance liquid chromatography gradient elution, collecting the eluate, and obtaining the long-chain diterpene stellera chamaejasme toxin A at 48.2 minutes.
In the first step, 8ml to 12ml of methanol is added to 1g of the Japanese stellera root.
In the fourth step, the high performance liquid chromatography eluent is a mixed solution of methanol and water, wherein the volume ratio of the methanol to the water is 75:25.
The second technical scheme of the invention is realized by the following measures: the preparation method of the long-chain diterpenoid stellera chamaejasme A is carried out according to the following steps: firstly, crushing radix euphorbiae lathyris, adding methanol, soaking for 3 to 4 hours at room temperature, heating and reflux-extracting for 3 times at 50 to 60 ℃ for 1 to 3 hours each time, combining the reflux extracting solutions each time, decompressing and recovering and concentrating to obtain radix euphorbiae lathyris extract; dispersing the radix euphorbiae lathyris extract into suspension by using water, sequentially extracting with dichloromethane and ethyl acetate, concentrating the extract to sequentially obtain dichloromethane part extract and ethyl acetate part extract; step three, taking the extract of the dichloromethane part, and performing gradient elution and separation by using a silica gel column to obtain 8 fractions, wherein the gradient eluent of the silica gel column comprises dichloromethane and methanol, and the volume ratio of the dichloromethane to the methanol is 100:1, 50:1, 30:1, 20:1, 10:1, 5:1, 3:1 and 1:1 in sequence; and fourthly, purifying and separating the 3 rd fraction in the 8 obtained fractions after high performance liquid chromatography gradient elution, collecting the eluate, and obtaining the long-chain diterpene stellera chamaejasme toxin A at 48.2 minutes.
The following is a further optimization and/or improvement of the second technical scheme of the invention:
in the first step, 8ml to 12ml of methanol is added to 1g of the Japanese stellera root.
In the fourth step, the high performance liquid chromatography eluent is a mixed solution of methanol and water, wherein the volume ratio of the methanol to the water is 75:25.
The third technical scheme of the invention is realized by the following measures: application of long-chain diterpene stellera chamaejasme A in preparing medicine for preventing liver cancer is provided.
The fourth technical scheme of the invention is realized by the following measures: application of long-chain diterpene stellera chamaejasme A in preparing medicine for preventing liver cancer is provided.
The fifth technical scheme of the invention is realized by the following measures: application of long-chain diterpene stellera chamaejasme A in preparing medicines for inhibiting or/and killing liver cancer HepG cells is provided.
The invention discloses a compound long-chain diterpenoid stellera chamaejasme A for the first time, and the long-chain stellera chamaejasme A has a strong inhibition effect on HepG human liver cancer cells, so that the long-chain stellera chamaejasme A is applied as a potential anti-tumor drug.
Drawings
FIG. 1 shows the long chain diterpene stellera chamaejasme A of the present invention 1 H-NMR spectrum.
FIG. 2 shows the long chain diterpene stellera chamaejasme A of the present invention 13 C-APT spectrogram.
Detailed Description
The present invention is not limited by the following examples, and specific embodiments can be determined according to the technical scheme and practical situations of the present invention. The various chemical reagents and chemicals mentioned in the present invention are all commonly known in the art unless specifically stated otherwise.
The invention is further described below with reference to examples:
example 1: the chemical structural formula of the long-chain diterpene stellera chamaejasme A is
。
Example 2: as an optimization of the above examples, the long chain diterpene stellera chamaejasme a was obtained as follows: firstly, crushing radix euphorbiae lathyris, adding methanol, soaking for 3 to 4 hours at room temperature, heating and reflux-extracting for 3 times at 50 to 60 ℃ for 1 to 3 hours each time, combining the reflux extracting solutions each time, decompressing and recovering and concentrating to obtain radix euphorbiae lathyris extract; dispersing the radix euphorbiae lathyris extract into suspension by using water, sequentially extracting with dichloromethane and ethyl acetate, concentrating the extract to sequentially obtain dichloromethane part extract and ethyl acetate part extract; step three, taking the extract of the dichloromethane part, and performing gradient elution and separation by using a silica gel column to obtain 8 fractions, wherein the gradient eluent of the silica gel column comprises dichloromethane and methanol, and the volume ratio of the dichloromethane to the methanol is 100:1, 50:1, 30:1, 20:1, 10:1, 5:1, 3:1 and 1:1 in sequence; and fourthly, purifying and separating the 3 rd fraction in the 8 obtained fractions after high performance liquid chromatography gradient elution, collecting the eluate, and obtaining the long-chain diterpene stellera chamaejasme toxin A at 48.2 minutes.
Example 3: as an optimization of the above example, in the first step, 8ml to 12ml of methanol was added per 1g of the Japanese stellera root.
Example 4: as an optimization of the above embodiment, in the fourth step, the high performance liquid chromatography eluent is a mixed solution of methanol and water, wherein the volume ratio of methanol to water is 75:25.
Example 5: the preparation method of the long-chain diterpenoid stellera chamaejasme A is carried out according to the following steps: firstly, crushing radix euphorbiae lathyris, adding methanol, soaking for 3 to 4 hours at room temperature, heating and reflux-extracting for 3 times at 50 to 60 ℃ for 1 to 3 hours each time, combining the reflux extracting solutions each time, decompressing and recovering and concentrating to obtain radix euphorbiae lathyris extract; dispersing the radix euphorbiae lathyris extract into suspension by using water, sequentially extracting with dichloromethane and ethyl acetate, concentrating the extract to sequentially obtain dichloromethane part extract and ethyl acetate part extract; step three, taking the extract of the dichloromethane part, and performing gradient elution and separation by using a silica gel column to obtain 8 fractions, wherein the gradient eluent of the silica gel column comprises dichloromethane and methanol, and the volume ratio of the dichloromethane to the methanol is 100:1, 50:1, 30:1, 20:1, 10:1, 5:1, 3:1 and 1:1 in sequence; and fourthly, purifying and separating the 3 rd fraction in the 8 obtained fractions after high performance liquid chromatography gradient elution, collecting the eluate, and obtaining the long-chain diterpene stellera chamaejasme toxin A at 48.2 minutes.
Example 6: the application of the long-chain diterpenoid stellera chamaejasme A in preparing medicaments for preventing liver cancer.
Example 7: the application of the long-chain diterpenoid stellera chamaejasme A in preparing medicaments for preventing liver cancer.
Example 8: the application of the long-chain diterpenoid stellera chamaejasme A in preparing medicines for inhibiting or/and killing HepG human hepatoma cells.
The long-chain diterpenoid stellera chamaejasme A is subjected to an in-vitro anti-tumor pharmacodynamics experiment, and the in-vitro anti-tumor pharmacodynamics experiment utilizes an MTT colorimetric method.
Taking long-chain diterpene stellera chamaejasme A as an experimental group, taking Cisplatin (Cisplatin) as a control group, setting a blank group at the same time, selecting HepG-2 (human gastric cancer cells) cells as experimental objects in the experimental group, the control group and the blank group, after dilution of a culture medium, inoculating the culture medium into a 96-well plate at the density of 4X 105, and after normal culture for 24 hours in an incubator with 100 mu L of each well, adding corresponding medicines into each group to ensure that the final concentration of the medicines in each group is respectively 12.5 mu g/mL (1 group), 25 mu g/mL (2 group), 50 mu g/mL (3 group), 100 mu g/mL (4 group), 200 mu g/mL (5 group), and setting 5 concentrations in total, wherein each concentration is 3 multiple wells; after 48 hours of incubation, 10 μl of MTT was added to each well for staining; after the culture is continued for four hours, the original culture solution is sucked and removed, 150 mu L of DMSO is added into each hole, the mixture is placed on a shaking table and oscillated for 10 minutes at a low speed to enable crystals to be fully dissolved, an optical density value is detected at a wavelength of 570nm of an ELISA (enzyme-linked immunosorbent assay) instrument, 50% inhibition concentration (IC 50, mu g/mL) is calculated according to the optical density value, and the calculation method for calculating the IC50 of the optical density value is a known technology. The IC50 of the experimental group and the control group to the HepG human liver cancer cell is shown in Table 3. The data in Table 3 shows that the stellera chamaejasme A has a strong inhibition effect on HepG human liver cancer cells.
In conclusion, the invention discloses a compound long-chain diterpenoid stellera chamaejasme A for the first time, and the long-chain stellera chamaejasme A has a strong inhibition effect on human HepG liver cancer cells, so that the long-chain stellera chamaejasme A is applied as a potential anti-tumor drug.
The technical characteristics form the embodiment of the invention, have stronger adaptability and implementation effect, and can increase or decrease unnecessary technical characteristics according to actual needs so as to meet the requirements of different situations.
Claims (10)
1. A long-chain diterpene stellera chamaejasme A is characterized in that the chemical structural formula is
。
2. The long-chain diterpene stellera chamaejasme A according to claim 1, characterized in that it is obtained according to the following method: firstly, crushing radix euphorbiae lathyris, adding methanol, soaking for 3 to 4 hours at room temperature, heating and reflux-extracting for 3 times at 50 to 60 ℃ for 1 to 3 hours each time, combining the reflux extracting solutions each time, decompressing and recovering and concentrating to obtain radix euphorbiae lathyris extract; dispersing the radix euphorbiae lathyris extract into suspension by using water, sequentially extracting with dichloromethane and ethyl acetate, concentrating the extract to sequentially obtain dichloromethane part extract and ethyl acetate part extract; step three, taking the extract of the dichloromethane part, and performing gradient elution and separation by using a silica gel column to obtain 8 fractions, wherein the gradient eluent of the silica gel column comprises dichloromethane and methanol, and the volume ratio of the dichloromethane to the methanol is 100:1, 50:1, 30:1, 20:1, 10:1, 5:1, 3:1 and 1:1 in sequence; and fourthly, purifying and separating the 3 rd fraction in the 8 obtained fractions after high performance liquid chromatography gradient elution, collecting the eluate, and obtaining the long-chain diterpene stellera chamaejasme toxin A at 48.2 minutes.
3. The long-chain diterpene stellera chamaejasme A of claim 2, wherein 8ml to 12ml of methanol is added per 1g of the stellera chamaejasme in the first step.
4. A long chain diterpene stellera chamaejasme toxin a according to claim 2 or 3, characterized in that in the fourth step, the high performance liquid chromatography eluent is a mixture of methanol and water, wherein the volume ratio of methanol to water is 75:25.
5. The preparation method of the long-chain diterpenoid stellera chamaejasme A is characterized by comprising the following steps of: firstly, crushing radix euphorbiae lathyris, adding methanol, soaking for 3 to 4 hours at room temperature, heating and reflux-extracting for 3 times at 50 to 60 ℃ for 1 to 3 hours each time, combining the reflux extracting solutions each time, decompressing and recovering and concentrating to obtain radix euphorbiae lathyris extract; dispersing the radix euphorbiae lathyris extract into suspension by using water, sequentially extracting with dichloromethane and ethyl acetate, concentrating the extract to sequentially obtain dichloromethane part extract and ethyl acetate part extract; step three, taking the extract of the dichloromethane part, and performing gradient elution and separation by using a silica gel column to obtain 8 fractions, wherein the gradient eluent of the silica gel column comprises dichloromethane and methanol, and the volume ratio of the dichloromethane to the methanol is 100:1, 50:1, 30:1, 20:1, 10:1, 5:1, 3:1 and 1:1 in sequence; and fourthly, purifying and separating the 3 rd fraction in the 8 obtained fractions after high performance liquid chromatography gradient elution, collecting the eluate, and obtaining the long-chain diterpene stellera chamaejasme toxin A at 48.2 minutes.
6. The long-chain diterpene stellera chamaejasme A of claim 5, wherein 8ml to 12ml of methanol is added per 1g of the stellera chamaejasme in the first step.
7. The long-chain diterpene stellera chamaejasme A according to claim 5 or 6, wherein in the fourth step, the high performance liquid chromatography eluent is a mixed solution of methanol and water, wherein the volume ratio of methanol to water is 75:25.
8. Use of the long-chain diterpene stellera chamaejasme a according to any one of claims 1-4 in the manufacture of a medicament for preventing liver cancer.
9. Use of the long-chain diterpene stellera chamaejasme a according to any one of claims 1-4 in the manufacture of a medicament for preventing liver cancer.
10. Use of the long-chain diterpene stellera chamaejasme a according to any one of claims 1 to 4 in the manufacture of a medicament for inhibiting or/and killing HepG human hepatoma cells.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116854704A (en) * | 2023-07-06 | 2023-10-10 | 沈阳药科大学 | Daphnane diterpenoid derivative with anti-liver cancer activity and preparation method and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009096655A1 (en) * | 2008-01-31 | 2009-08-06 | Ewha University-Industry Collaboration Foundation | Composition comprising the compound isolated from the flower extract of daphne genkwa for preventing and treating cancer disease and the use thereof |
| CN101704826A (en) * | 2009-09-15 | 2010-05-12 | 沈阳药科大学 | Chinese medicinal lilac daphne flower bud diterpene ortho-ester compounds |
| KR20140015798A (en) * | 2012-07-25 | 2014-02-07 | 서울대학교산학협력단 | Effective anticancer drugs against gefitinib-resistant human lung cancer cells comprising the daphnane diterpenoid compound |
| CN106432263A (en) * | 2015-08-11 | 2017-02-22 | 复旦大学 | Preparation method of total diterpenoids of stellera chamaejasme L. and application of total diterpenoids in medicine preparation |
| CN110538243A (en) * | 2018-05-29 | 2019-12-06 | 复旦大学 | Preparation method of active total diterpene in Thymelaeaceae plant and application thereof in pharmacy |
| CN112538088A (en) * | 2020-12-22 | 2021-03-23 | 中山大学 | Daphnane diterpene for resisting prostatic cancer and preparation method thereof |
-
2023
- 2023-05-06 CN CN202310504026.9A patent/CN116589476A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009096655A1 (en) * | 2008-01-31 | 2009-08-06 | Ewha University-Industry Collaboration Foundation | Composition comprising the compound isolated from the flower extract of daphne genkwa for preventing and treating cancer disease and the use thereof |
| CN101704826A (en) * | 2009-09-15 | 2010-05-12 | 沈阳药科大学 | Chinese medicinal lilac daphne flower bud diterpene ortho-ester compounds |
| KR20140015798A (en) * | 2012-07-25 | 2014-02-07 | 서울대학교산학협력단 | Effective anticancer drugs against gefitinib-resistant human lung cancer cells comprising the daphnane diterpenoid compound |
| CN106432263A (en) * | 2015-08-11 | 2017-02-22 | 复旦大学 | Preparation method of total diterpenoids of stellera chamaejasme L. and application of total diterpenoids in medicine preparation |
| CN110538243A (en) * | 2018-05-29 | 2019-12-06 | 复旦大学 | Preparation method of active total diterpene in Thymelaeaceae plant and application thereof in pharmacy |
| CN112538088A (en) * | 2020-12-22 | 2021-03-23 | 中山大学 | Daphnane diterpene for resisting prostatic cancer and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| HAI-LONG JIANG等: "A new highly oxygenated daphnane diterpene esters from the flower buds of Daphne genkwa", 《NATURAL PRODUCT RESEARCH》, vol. 29, no. 20, 31 December 2015 (2015-12-31), pages 1878 - 1883 * |
| 何晓艳等: "天山假狼毒的化学成分研究", 《天然产物研究与开发》, vol. 34, 31 December 2022 (2022-12-31), pages 1345 - 1351 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116854704A (en) * | 2023-07-06 | 2023-10-10 | 沈阳药科大学 | Daphnane diterpenoid derivative with anti-liver cancer activity and preparation method and application thereof |
| CN116854704B (en) * | 2023-07-06 | 2024-05-07 | 沈阳药科大学 | Daphnane diterpenoid derivative with anti-liver cancer activity and preparation method and application thereof |
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