CN103432144A - Application of withanolide compound in preparation of drug or healthcare product for treating or preventing tumors and neurodegenerative diseases - Google Patents
Application of withanolide compound in preparation of drug or healthcare product for treating or preventing tumors and neurodegenerative diseases Download PDFInfo
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Abstract
The invention discloses application of a withanolide compound in preparation of a drug or a healthcare product for treating or preventing tumors and neurodegenerative diseases. The withanolide compound has structural formulas as shown in formula I and optical isomers thereof. The research indicates that the withanolide compounds can be used for activating an Nrf2 signal channel, up regulating expression of NrF2 and downstream antioxidant and II-phase detoxifying enzymes thereof, strengthening the level of glutathione in cells, increasing reducing capacity in cells, promoting elimination of active carbon, restraining lipid peroxidation and lowering cytotoxicity caused by cancerogen arsenic and nerve cell toxicity induced by active oxygen H2O2 to show good chemical prevention effect. And therefore, the withanolide compound and nightshade extract including the withanolide compound have the potential of becoming a chemical prophylactic drug and the healthcare product, and can be used for preparing the corresponding oral preparation and injection by being used as the main ingredient, and also can be used for preventing and treating tumors and neurodegenerative diseases.
Description
Technical field
The present invention relates to the new purposes of liquor-saturated eggplant lactone (withanolides) compound, the plant of Solanaceae extract that relates in particular to this compounds and contain this compounds is in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or the application in health product.
Background technology
Along with social development, human living standard's raising and the improvement of medical condition, human longevity has obtained significant prolongation, but simultaneously, the sickness rate of malignant tumor, neurodegenerative diseases also improves year by year, and the serious threat human health, brings white elephant to country and society.Realize above-mentioned disease effectively under the prerequisite for the treatment of there is no active drug, prophylacticly become effective coping strategy.
Chemoprophylaxis (chemoprevention) refers to that be main measure to asymptomatic use medicine, nutrient (comprising inorganic salt), biological preparation or other natural materials as one-level, secondary prevention, the ability of raising crowd resist the disease, to prevent the generation of some disease.Research shows, adopts chemopreventive agent (medicine) (chemopreventive agents) can significantly reduce the incidence rate of the disease of some.For example, the generation of aspirin prevention of cardiac, apoplexy, tamoxifen can reduce the sickness rate of breast carcinoma.The chemical composition of natural origin, for example sulforaphen, resveratrol, curcumin, lycopene, garlicin, cinnamic aldehyde, be proved to be effective chemopreventive agent (medicine), sickness rate (Surh, Nature, 2003 of can enhancing immunity and reducing some disease, 3,768-780).
Studies confirm that nuclear factor Nrf2(Nuclear factor-erythroid2-related factor2) signal path and chemoprophylaxis closely related, be the target spot of chemopreventive agent (medicine) effect.Nrf2 is the important transcription factor of regulating cellular oxidation reduction balance, by with antioxidase and II phase detoxication enzyme promoter region antioxidation, reacting original paper (ARE) in conjunction with the regulating cell redox equilibrium, its target gene comprises the II phase detoxication enzyme of coding GST, UGT, γ GCS, NQO1, and the endogenous antioxidation albumen such as GCL, HO-1.When body is exposed under electrophilicity foreign body, chemical carcinogen, endogenous oxidant equivalent damage body material, Nrf2 just can activate antioxidase and II phase detoxication enzyme is removed nuisance, protection body function (Lau et al.; Pharmacol.Res.; 2008,58,262-270).
Under oxidative stress status, face the infringement to body of endogenous and exogenous poisonous substance, utilize exogenous Nrf2 agonist to raise body Nrf2 level, can enhancing body self-defense ability, for the generation of prophylaxis of tumours, neurodegenerative diseases significant (Magesh et al., Med.Res.Rev., 2012,32,4,687-726).Activate the Nrf2 signal path, can raise II phase detoxication enzyme level, remove carcinogen or reduce its toxicity, suppress DNA damage, gene mutation that carcinogen is induced, thus the generation of prophylaxis of tumours.Raise Nrf2 and express, can increase the glutathion inside cell level, strengthen activities of antioxidant enzymes, active oxygen in scavenger cell, suppress the cytolipin peroxidating, reduces the sickness rate of the neurodegenerative diseases such as Alzheimer's disease and parkinson.
Studies confirm that the number of chemical prophylactic agent is the Nrf2 agonist, by activating Nrf2 signal path performance chemoprophylaxis effect, comprise sulforaphen, resveratrol, the compounds such as curcumin, cinnamic aldehyde.Nrf2 is considered to find the important target spot of chemoprophylactic drug, and the Nrf2 agonist be also the important sources that develops chemoprophylactic drug (Jeong et al, Antioxid.Redox Signal., 2006,8,99-106).
Liquor-saturated eggplant lactone (withanolides) compound is a class lumistane type steroidal, and the characteristic structure is its 22 carbon and 26 carbon, or the δ of 23 carbon and 26 carbon formation-or gamma lactone ring (as follows).This compounds mainly is present in plant of Solanaceae, have the pharmacological actions such as antitumor, antimicrobial, antiinflammatory, acetylcholine esterase inhibition, immunomodulating (Chen et al, Nat.Prod.Rep., 2011,28,705-740).
4 beta-hydroxy withanolide Es (4 β-hydroxywithanolide E) are to separate the steroidal compounds obtained from the Solanaceae monkey flower, the unformed powder that is white in color, and molecular formula is C
28h
38o
8, molecular weight is 525, is soluble in the organic solvents such as methanol, ethyl acetate, its structural formula is as follows:
At present, the research for liquor-saturated eggplant lactone compound mainly concentrates on the antitumor action that this compounds is stronger.Up to now, in many bibliographical informations, have no the report that this compounds activates the Nrf2 signal path, also have no liquor-saturated eggplant lactone compound as chemopreventive agent (medicine) research and development, and the report that prevents and treat for tumor, neurodegenerative diseases.
Summary of the invention
For above-mentioned prior art, the invention provides a kind of new purposes of liquor-saturated eggplant lactone compound---liquor-saturated eggplant lactone compound and the plant of Solanaceae extract that contains this compounds are preparing treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or the application in health product.
The present invention is achieved by the following technical solutions:
Liquor-saturated eggplant lactone compound has the structural formula shown in general formula I and optical isomer thereof:
Wherein, 1 is carbonyl, and 5,6 is two keys, and 22,26 form delta-lactone ring, substituent R
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10and R
11respectively independently selected from H, OH, SH, OMe, CN, OEt, NH
2, NO
3, F, Cl, Br, carbonyl, two key, epoxy radicals.
Compound shown in described general formula I comprises 4 beta-hydroxy withanolide Es (4 β-hydroxywithanolideE) withaferin A, withanolide D, 4 β-hydroxy-5 β, 6 β-epoxy-1-oxo-22R-witha-2,14,24-trienolide, 17 α-hydroxy-27-deoxy-withaferin A-4-acetate, physapulin A, withangulatin I, ajugin C, withacoagulin E, structural formula is as follows respectively:
In the present inventor's early-stage Study, from the Solanaceae monkey flower, separation and chemical constitution are modified and have been obtained nearly 30 liquor-saturated eggplant lactone compounds, and the Nrf2 activation of this compounds is conducted in-depth research.Research shows, liquor-saturated eggplant lactone compound has the Nrf2 agonism, its activity intensity and its structure present dependency, α in its structure, β-unsaturated lactone structure is essential groups, can be combined and change its configuration by the sulfydryl on Keap1, by activating Nrf2, transcribe and suppress the Nrf2 degraded and activate this signal path.Research is found, this compounds can increase the glutathion inside cell level, increase reducing power in cell, promote the removing of active oxygen, suppress lipid peroxidation, and can reduce the cytotoxicity that carcinogen arsenic is induced, show the ability that suppresses cell carcinogenesis, suppress the neural cell injury that active oxygen is induced, show the potentiality of prevention of neurodegenerative diseases.Therefore, the plant of Solanaceae extract that can take liquor-saturated eggplant lactone compound or contain this compounds is raw material, for the preparation of the health product of prophylaxis of tumours, neurodegenerative diseases, or for the preparation of the medicine for the treatment of tumor, neurodegenerative diseases.During concrete application, can be by liquor-saturated eggplant lactone compound or/and the plant of Solanaceae extract that contains this constituents be made oral formulations or injection.
The described plant of Solanaceae extract that contains liquor-saturated eggplant lactone compound, prepare by the following method: plant of Solanaceae is pulverized, by 0～95% ethanol (percentage by volume) reflux, extract, 1～8 time, each solvent load is 1～20 times of medical material weight, each extraction time is 0.5～10 hour, and merge extractive liquid, filters, carry out concentrating under reduced pressure or vacuum drying or spray drying or lyophilization, obtain the plant of Solanaceae extract.
Described plant of Solanaceae comprises Physalis pubescens L. (Physialis pubescens L.), Calyx seu fructus physalis (Physalis alkekengil var.francheti), fruitlet Calyx seu fructus physalis (Physialis peruviana), Withania kansuensis (Withania kansuensis).
Below adopt 4 beta-hydroxy withanolide Es as representative compound, carry out the research of this compounds to the effect of Nrf2 signal path:
Select human breast carcinoma MDA-MB-231 cell as detecting cell, estimate the effect of 4 beta-hydroxy withanolide Es to the Nrf2 signal path.Model the MDA-MB-231-Luc cell line of the luciferase plasmids that can stably express relies on containing ARE, and estimate its effect to Nrf2, result shows that 4 beta-hydroxy withanolide Es can promote Nrf2 to transcribe (Fig. 1), and further with luciferase reporter gene, has proved conclusively its activation to the Nrf2 signal path (Fig. 2).The western blot analysis result shows, 4 beta-hydroxy withanolide Es can raise the expression of Nrf2 albumen, and can promote the expression (Fig. 3) of downstream antioxidation and II phase detoxication enzyme albumen NQO1 and γ GCS.Cellular immunofluorescence is tested and is shown, 4 beta-hydroxy withanolide Es can promote the Nrf2 transposition to enter core, the one-step activation downstream gene (Fig. 4) of going forward side by side.
Select people's normal lung epithelial cell Beas-2B, detected the impact of 4 beta-hydroxy withanolide Es on the glutathion inside cell level.The result demonstration, this compound can increase glutathion inside cell level (Fig. 5), strengthens reducing power and Scavenger of ROS ability in cell.
The cytotoxicity model of selecting carcinogen arsenic to induce, estimate the protective effect of 4 beta-hydroxy withanolide Es to people's normal lung epithelial cell Beas-2B.Process its survival rate of cell through 4 beta-hydroxy withanolide Es and be significantly higher than not dosing processed group, prove that this compound can significantly suppress the cytotoxicity that trivalent arsenic is induced, and at 50nM, cell is produced to best protection effect (Fig. 6).This result proves, 4 beta-hydroxy withanolide Es can be used as prevention and the treatment for tumor of chemoprophylactic drug or health product.
Select active oxygen H
2o
2the cytotoxicity model of inducing, estimate the protective effect of 4 beta-hydroxy withanolide Es to neurocyte PC12.Result shows that 4 beta-hydroxy withanolide Es can suppress H
2o
2the toxicity produced, improve cells survival rate (Fig. 7).The many toxicity with the active oxygen generation of the generation of neurodegenerative diseases is closely related, so this result proves that 4 beta-hydroxy withanolide Es can be used as prevention and the treatment for neurodegenerative diseases of chemoprophylactic drug or health product.
The accompanying drawing explanation
Fig. 1: the fluorescein report high throughput screening assay that antioxidation reaction original paper (ARE) relies on shows that 4 beta-hydroxy withanolide Es can activate the Nrf2 signal path.
Fig. 2: the luciferase reporter gene activity test shows that 4 beta-hydroxy withanolide Es can activate the Nrf2 signal path.
Fig. 3: western blot analysis shows that 4 beta-hydroxy withanolide Es can activate its downstream gene of Nrf2 at protein level.
Fig. 4: immunofluorescence test shows that 4 beta-hydroxy withanolide Es can promote the transposition of Nrf2 albumen to enter core, wherein, A-C is the blank group without compound treatment, and A shows the position of Nrf2 albumen, B shows nuclear position, and C shows that Nrf2 albumen is arranged in perinuclear Cytoplasm; D-F is 4 beta-hydroxy withanolide E processed group, and D shows the position of Nrf2 albumen, and E shows nuclear position, and F shows that Nrf2 albumen overlaps with the nucleus position, and after compound treatment, transposition enters core; The positive contrast sulforaphen of G-I matched group, G shows the position of Nrf2 albumen, and H shows nuclear position, and I shows that Nrf2 albumen overlaps with the nucleus position, and sulforaphen is processed rear transposition and is entered core.
Fig. 5: 4 beta-hydroxy withanolide Es can increase the glutathion inside cell level.
Fig. 6: 4 beta-hydroxy withanolide Es can reduce the cytotoxicity that arsenic is induced, and wherein, A is the Cytotoxic protective effect that variable concentrations 4 beta-hydroxy withanolide Es (10 μ M to 500 μ M) are induced 40 μ M arsenic; B is the Cytotoxic protective effect that 50 μ M4 beta-hydroxy withanolide Es are induced variable concentrations arsenic (10 μ M to 500 μ M).
Fig. 7: 4 beta-hydroxy withanolide Es can reduce H
2o
2the cytotoxicity of inducing, wherein, A is that variable concentrations 4 beta-hydroxy withanolide Es (10 μ M to 500 μ M) are to 200 μ MH
2o
2the Cytotoxic protective effect of inducing; B is that 50 μ M4 beta-hydroxy withanolide Es are to variable concentrations H
2o
2the Cytotoxic protective effect that (50 μ M to 500 μ M) induces.
The specific embodiment
Below in conjunction with embodiment, the present invention is further illustrated.
Embodiment 1:4 beta-hydroxy withanolide E strengthens the luciferase reporter gene expression that antioxidation reaction original paper (ARE) relies on
Method: structure and the cultivation of (1) human breast cancer cell MDA-MB-231-Luc cell line
Human breast cancer cell MDA-MB-231, purchased from US mode culture collection warehousing (ATCC), adopts the MEM culture medium containing 10% hyclone (FBS), 2mMHEPES and 6ng/mL insulin, is placed in 37 ℃, 5%CO
2in incubator, cultivate.The sequence that contains antioxidation reaction original paper (ARE) from people NQO1 upstream region of gene of a 39bp is inserted to the cloning site of luciferase plasmids (pGL4.22[1uc2CP/Puro]).Adopt transfection reagent Lipofectamine Plus that the ARE luciferase plasmids is transfected into to the MDA-MB-231 cell.After 48h, with the cell of the Screening of Media transfection success that contains puromycin, build the MDA-MB-231-Luc cell line of stably express ARE luciferase.
(2) the fluorescence report high throughput screening assay that ARE relies on
The MDA-MB-231 cell is inoculated on 96 orifice plates, the testing compound that adds variable concentrations after 24 hours, process 16 hours, adopt cell pyrolysis liquid [0.1M potassium phosphate and 1mM dithiothreitol, DTT] cell lysis, with detecting liquid (25mM glycylglycine, 15mM magnesium sulfate, 500 μ MATP, 250 μ M fluoresceins and 250 μ M coenzyme As), measure fluorescence intensity.
Result: as shown in Figure 1,4 beta-hydroxy withanolide Es can strengthen the fluorescence intensity that ARE relies on, and present dose-dependent increasing at 0.13 μ M in 4 μ M scopes, and its activity is better than the positive control drug sulforaphen, showing that this compound can activate Nrf2 and transcribe, is a Nrf2 agonist.
Embodiment 2:4 beta-hydroxy withanolide E strengthens the luciferase reporter gene expression that antioxidation reaction original paper (ARE) relies on: luciferase reporter gene detects test
The luciferase expression plasmid ARE built relied on transfection reagent Lipofectamine Plus (pGL4.22[1uc2CP/Puro]) and renilla luciferase expression vector [pGL4.74[hRluc/TK] transfection simultaneously MDA-MB-231 cell.After 24h, add the variable concentrations testing compound to process 16h, adopt the luciferase reporter gene detection system detection LUC Photinus pyralis LUC Photinus pyralis FL of Promega company and the activity of renilla luciferase, wherein the activity of renilla luciferase is as internal reference.
Result: luciferase reporter gene detects test usings the activity of renilla luciferase as internal reference, result as shown in Figure 2,4 beta-hydroxy withanolide Es can dose-dependently induce the luciferase reporter gene that ARE relies on to express, the activity of the intensity of its 1 μ M and 2.5 μ M positive control medicine sulforaphen is suitable, has further proved that this compound is strong Nrf2 agonist.
Embodiment 3:4 beta-hydroxy withanolide E raises Nrf2 and reaches the expression with downstream gene protein level
Method: western blot analysis (Western blot) detects the variation of protein level in cell
The MDA-MB-231 cell is inoculated in diameter 35mm culture dish, after being cultured to density and reaching 70%～80%, add the testing compound of variable concentrations to process 16h, PBS washing 2 times, add cell pyrolysis liquid (50 μ g/ml aprotiniies, 0.5mM Phenylmethanesulfonyl fluoride, the 1mM sodium vanadate, the 10mM sodium fluoride, 10mM β-phosphoglycerol), collect albumen and adopt the Bradford method to measure protein concentration.Each sample thief albumen (100 μ g) loading, SDS-PAGE protein isolate component also adopts the electrotransfer method that protein band is transferred on cellulose nitrate film.Thin film is after the defatted milk powder solution room temperature sealing 1h of TBS preparation 5%, respectively with 4 ℃ of overnight incubation of each testing protein antibody.After TBS washing, add respectively horseradish peroxidase two anti-hatch 1h after, carry out analysis of protein with enhancement mode ECL chemiluminescence.
Result: as shown in Figure 3, cell is after 4 beta-hydroxy withanolide Es are processed 16h, Nrf2 and downstream antioxidation thereof and II phase detoxication enzyme albumen NQO1 and γ GCS protein level present dose dependent to be increased, and confirms that this compound can plan the Nrf2 signal path on protein level.
Embodiment 4:4 beta-hydroxy withanolide E promotes the Nrf2 transposition to enter core
Method: the position of immuno-fluorescence assay Nrf2 in cell
The MDA-MB-231 cell is inoculated in 24 orifice plates of placing slide, after cell attachment, add testing compound to process 8 hours, PBS washing 2 times, add methanol to fix 4 hours, PBS washing 2 times, add the Nrf2 antibody incubation 1 hour, PBS washing 3 times, add DAPI and Alex488 fluorescence two to resist and hatch 50 minutes, adopt Zeiss Observer.Z1 fluorescence microscope also to take pictures.
Result: the immunofluorescence result shows (Fig. 4), under the cell normal condition, Nrf2 is arranged in Cytoplasm, adds 4 beta-hydroxy withanolide Es and positive control sulforaphen to process after 8 hours, the Nrf2 transposition enters nucleus, and further with ARE, is combined and activates its downstream gene.The result confirmation, 4 beta-hydroxy withanolide Es can activate the Nrf2 signal path.
Embodiment 5:4 beta-hydroxy withanolide E increases the glutathion inside cell level
Method: the cultivation of (1) people's normal lung epithelial cell Beas-2B cell
People's normal lung epithelial cell Beas-2b is purchased from US mode culture collection warehousing (ATCC), adopt Ham ' sF-12 culture medium, and add wherein six kinds of cell growth factor, comprise the 2.0mg/ml insulin, 10 μ g/ml epidermal growth factors, 2.5mg/ml transferring, 0.05mM dexamethasone, 10 μ g/ml cholera toxins, and6.0mg/ml endothelial cell growth supplement, be placed in 37 ℃, 5%CO
2in incubator, cultivate.
(2) mensuration of glutathion inside cell content
The Beas-2b cell is inoculated in diameter 35mm culture dish, after being cultured to density and reaching 70%～80%, add the testing compound of variable concentrations to process 24 hours, PBS washing 2 times, add 0.5mL50mM sodium phosphate and 1mMEDTA buffer to receive cell, ultrasonic 1min, centrifugal 15 minutes of 10000g, get supernatant, according to glutathion, measure the operation of test kit description, 412nm measures absorbance and calculates glutathione content.
Result: as shown in Figure 5,4 beta-hydroxy withanolide Es can significantly increase the glutathion inside cell level, strengthen reducing power in cell.
Embodiment 6:4 beta-hydroxy withanolide E can suppress the toxicity of trivalent arsenic to people's pulmonary branches tracheal epithelial cell Beas-2b
Method: mtt assay is measured the Cytotoxic protective effect that compound is induced arsenic
The Beas-2b cell is inoculated on 96 orifice plates, adds the variable concentrations testing compound to process 16 hours, then add the arsenic of variable concentrations and testing compound to process 24 hours, after adding MTT3 hour, 590nm measures absorbance and calculates the cells survival rate.
Result: as shown in Figure 6; adopt respectively 10; 25; 50; 100 and the 4 beta-hydroxy withanolide E pretreatment cell of 500nM 16 hours, then add the arsenic of 40 μ M and 4 beta-hydroxy withanolide Es of respective concentration to process cell 24 hours, result shows that above-claimed cpd has protective effect to the Beas-2b cell; can suppress the cytotoxicity that arsenic is induced, wherein the effect of 50nM is the strongest.Adopt 50nM pretreatment cell 16 hours, then add the arsenic of variable concentrations and the 4 beta-hydroxy withanolide Es of 50nM to process cell 24 hours, its cells survival rate is apparently higher than not adding the medicine processed group.Result proves, 4 beta-hydroxy withanolide Es can suppress the toxicity that carcinogen arsenic is induced, and can be used in prevention and the treatment of tumor.
Embodiment 7:4 beta-hydroxy withanolide E can suppress the toxicity of H2O2 to neurocyte strain PC12
Method: the cultivation of (1) neurocyte PC12
Neurocyte strain PC12, purchased from US mode culture collection warehousing (ATCC), adopts the DMEM culture medium containing 15% hyclone (FBS), 100U/ml penicillin and 100U/ml streptomycin, is placed in 37 ℃, 5%CO
2in incubator, cultivate.
(2) mtt assay is measured compound to H
2o
2the Cytotoxic protective effect of inducing
The PC12 cell is inoculated on 96 orifice plates, adds the variable concentrations testing compound to process 16 hours, then add the arsenic of variable concentrations and testing compound to process 24 hours, after adding MTT3 hour, 590nm measures absorbance and calculates the cells survival rate.
Result: shown in Fig. 7, adopt respectively 10,25,50,100 and the 4 beta-hydroxy withanolide E pretreatment cell of 500nM 16 hours, then add the H of 200 μ M
2o
2process cell 24 hours with 4 beta-hydroxy withanolide Es of respective concentration, result shows that above-claimed cpd has protective effect to the PC12 cell, can suppress H
2o
2the cytotoxicity of inducing, wherein the effect of 100nM is the strongest.Adopt 100nM pretreatment cell 16 hours, then add the H of variable concentrations
2o
2process cell 24 hours with the 4 beta-hydroxy withanolide Es of 100nM, its cells survival rate is apparently higher than not adding the medicine processed group.Result proves, 4 beta-hydroxy withanolide Es can suppress active oxygen H
2o
2the neurotoxicity produced, can be used in prevention and the treatment of neurodegenerative diseases.
Embodiment 8: the preparation of plant of Solanaceae Physalis pubescens L. extract
Physalis pubescens L. (Physialis pubescensL.) 50kg, with 40% ethanol (percentage by volume) reflux, extract, of 10 times of medical material weight 4 times, each 6 hours, merge extractive liquid,, filtered, concentrating under reduced pressure, the concentrated solution spray drying, obtain, and yield is 7.3%.
Embodiment 9: the preparation of plant of Solanaceae Withania kansuensis extract
Withania kansuensis (Withania kansuensis) 50kg, with 70% ethanol (percentage by volume) reflux, extract, of 8 times of medical material weight 3 times, each 5 hours, merge extractive liquid,, filtered, concentrating under reduced pressure, the concentrated solution lyophilization, obtain, and yield is 8.3%.
Embodiment 10: the preparation of plant of Solanaceae Calyx seu fructus physalis extract
Calyx seu fructus physalis (Physalis alkekengil var.francheti) 50kg, with 75% ethanol (percentage by volume) reflux, extract, of 6 times of medical material weight 2 times, each 4 hours, merge extractive liquid,, filter concentrating under reduced pressure, the concentrated solution drying under reduced pressure, obtain, and yield is 5.3%.
Embodiment 11: the preparation of plant of Solanaceae fruitlet Calyx seu fructus physalis extract
Fruitlet Calyx seu fructus physalis (Physialis peruviana) 50kg, with 50% ethanol (percentage by volume) reflux, extract, of 5 times of medical material weight 4 times, each 6 hours, merge extractive liquid,, filtered, concentrating under reduced pressure, the concentrated solution vacuum drying, obtain, and yield is 7.0%.
Claims (7)
1. liquor-saturated eggplant lactone compound is in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or the application in health product, and wherein, liquor-saturated eggplant lactone compound has the structural formula shown in general formula I and optical isomer thereof:
Wherein, 1 is carbonyl, and 5,6 is two keys, and 22,26 form delta-lactone ring, substituent R
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10and R
11respectively independently selected from H, OH, SH, OMe, CN, OEt, NH
2, NO
3, F, Cl, Br, carbonyl, two key, epoxy radicals.
2. application according to claim 1, it is characterized in that: compound shown in described general formula I comprises 4 beta-hydroxy withanolide Es (4 β-hydroxywithanolide E), withaferin A, withanolide D, 4 β-hydroxy-5 β, 6 β-epoxy-1-oxo-22R-witha-2,14,24-trienolide, 17 α-hydroxy-27-deoxy-withaferinA-4-acetate, physapulinA, withangulatinI, ajuginC, withacoagulinE, structural formula is as follows respectively:
3. application according to claim 1 and 2 is characterized in that: while specifically applying, liquor-saturated eggplant lactone compound is added to medically acceptable adjuvant, make oral formulations or injection.
4. the plant of Solanaceae extract, in preparation treatment or prophylaxis of tumours, the medicine of neurodegenerative diseases or the application in health product, is characterized in that: contain the compound shown in general formula I or its optical isomer as claimed in claim 1 or 2 in this plant of Solanaceae extract.
5. plant of Solanaceae extract claimed in claim 4, it is characterized in that: prepare by the following method: plant of Solanaceae is pulverized, with 0～95% alcohol reflux 1～8 time, each solvent load is 1～20 times of medical material weight, each extraction time is 0.5～10 hour, and merge extractive liquid, filters, carry out concentrating under reduced pressure or vacuum drying or spray drying or lyophilization, obtain the plant of Solanaceae extract.
6. plant of Solanaceae extract according to claim 5, it is characterized in that: described plant of Solanaceae is selected from Physalis pubescens L. (Physialis pubescens L.), Calyx seu fructus physalis (Physalis alkekengil var.francheti), fruitlet Calyx seu fructus physalis (Physialis peruviana), Withania kansuensis (Withania kansuensis).
7. application according to claim 4 is characterized in that: while specifically applying, the plant of Solanaceae extract is added to medically acceptable adjuvant, make oral formulations or injection.
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| CN110545831A (en) * | 2017-04-27 | 2019-12-06 | 帝斯曼知识产权资产管理有限公司 | Use of extract of Withania SOMNIFERA for protecting against air pollution related diseases |
| CN107652350A (en) * | 2017-10-09 | 2018-02-02 | 沈阳药科大学 | A kind of withanolide II, extracting method and application thereof |
| CN110314169A (en) * | 2018-03-28 | 2019-10-11 | 中国医学科学院药物研究所 | Application of the withaferin A in preparation prevention or treatment glioblast tumor medicine |
| CN111377994A (en) * | 2018-12-28 | 2020-07-07 | 南开大学 | Seven withanolides compounds from cape gooseberry and preparation method and application thereof |
| CN111718393A (en) * | 2020-06-08 | 2020-09-29 | 天津中医药大学 | Withanolide compound and application thereof |
| CN111718393B (en) * | 2020-06-08 | 2022-05-24 | 天津中医药大学 | Withanolide compound and application thereof |
| CN112480203A (en) * | 2020-11-30 | 2021-03-12 | 浙江中医药大学 | Withanolide compound and preparation method and application thereof |
| CN112480203B (en) * | 2020-11-30 | 2021-09-14 | 浙江中医药大学 | Withanolide compound and preparation method and application thereof |
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