CN105687209B - Application of the Salvia Miltiorrhiza Monomer compound in preparation enhancing iPS characteristics of cell biology product - Google Patents
Application of the Salvia Miltiorrhiza Monomer compound in preparation enhancing iPS characteristics of cell biology product Download PDFInfo
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- CN105687209B CN105687209B CN201610104767.8A CN201610104767A CN105687209B CN 105687209 B CN105687209 B CN 105687209B CN 201610104767 A CN201610104767 A CN 201610104767A CN 105687209 B CN105687209 B CN 105687209B
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- monomer compound
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- salvia miltiorrhiza
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- 235000011135 Salvia miltiorrhiza Nutrition 0.000 title claims abstract description 25
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- 230000002708 enhancing effect Effects 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
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- 235000017276 Salvia Nutrition 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 18
- AZEZEAABTDXEHR-UHFFFAOYSA-M sodium;1,6,6-trimethyl-10,11-dioxo-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-2-sulfonate Chemical compound [Na+].C12=CC=C(C(CCC3)(C)C)C3=C2C(=O)C(=O)C2=C1OC(S([O-])(=O)=O)=C2C AZEZEAABTDXEHR-UHFFFAOYSA-M 0.000 claims abstract description 16
- 239000011734 sodium Substances 0.000 claims abstract description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 14
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- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
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- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/999—Small molecules not provided for elsewhere
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Transplantation (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Developmental Biology & Embryology (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to pharmaceutical technology fields, and in particular to a kind of application of Salvia Miltiorrhiza Monomer compound in preparation enhancing iPS characteristics of cell biology product.The Salvia Miltiorrhiza Monomer compound is at least one of root of red-rooted salvia phenolic acid B and tanshinone IIA sodium sulfonate, and the structural formula of the root of red-rooted salvia phenolic acid B and tanshinone IIA is as shown in formula I and formula II: the present invention also provides a kind of enhancing iPS characteristics of cell biology drugs.IPS is pre-processed by the Salvia Miltiorrhiza Monomer ingredient of various concentration in the present invention, the results show that sodium tanshinon Ⅱa silate and root of red-rooted salvia phenolic acid B can promote multipotency to induce stem cells hyperplasia, and root of red-rooted salvia phenolic acid B is more significant in the ability of this aspect.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of Salvia Miltiorrhiza Monomer compound is raw in preparation enhancing iPS cell
Application in object behavioural products.
Background technique
Radix Salviae Miltiorrhizae system Labiatae herbaceos perennial, Radix Salviae Miltiorrhizae Chang Peiwu is in treatment cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral infarction
In dead prescription.It has protective effect to secretion function of blood vessel endothelial cells, significantly inhibits artery sclerosis, and it is solid to reduce the total gallbladder of serum
The effects of alcohol, anti-ventricular hypertrophy, anti-oxidant, anti-arrhythmia.And cardiovascular patient often merges other diseases, and there are also anti-for Radix Salviae Miltiorrhizae
Inflammation, antiplatelet, anticoagulant, antithrombotic effect, can effectively improve the prognosis of patient.Therefore, Radix Salviae Miltiorrhizae is in cardiovascular disease
Prevention and treatment aspect has broad application prospects.
At present research confirm, inductive pluripotent stem cells (iPS) be by reprogramming body cell obtain have and embryo
A kind of multipotential stem cell of the similar hyperproliferation of stem cell and Multidirectional Differentiation potentiality is the important candidate dry of reparation necrotic myocardium
Cell.It cannot regenerate, limit after cardiac muscle of mammal cell damage (such as ischemic heart disease, atherosclerosis, hypertension)
The self-regeneration function of cardiac muscle has been made, and it is thin to be successfully divided into neuron similar to embryonic stem cell in vitro for iPS cell
Born of the same parents, Deiter's cells, cardiovascular cell and archaeocyte etc., therefore, iPS cell will future can be used for treating mind
A kind of effective intervention means through human diseases such as systemic disease, cardiovascular disease, reproductive diseases.
Summary of the invention
For overcome the deficiencies in the prior art, it is being made the primary purpose of the present invention is that providing a kind of Salvia Miltiorrhiza Monomer compound
Application in standby enhancing iPS characteristics of cell biology product.
Another object of the present invention is to provide a kind of enhancing iPS characteristics of cell biology drugs.
The purpose of the invention is achieved by the following technical solution:
A kind of application of Salvia Miltiorrhiza Monomer compound in preparation enhancing iPS characteristics of cell biology product, the Radix Salviae Miltiorrhizae
Monomeric compound is at least one of root of red-rooted salvia phenolic acid B and tanshinone IIA sodium sulfonate, the root of red-rooted salvia phenolic acid B and tanshinone IIA
Structural formula as shown in formula I and formula II:
The effective concentration of the root of red-rooted salvia phenolic acid B is preferably 2.5 × 10-5mol/L；
The effective concentration of the sodium tanshinon Ⅱa silate is preferably 150 μm of ol/L；
The Salvia Miltiorrhiza Monomer compound is preferably root of red-rooted salvia phenolic acid B；
A kind of enhancing iPS characteristics of cell biology drug includes above-mentioned root of red-rooted salvia phenolic acid B, tanshinone IIA sodium sulfonate or its medicine
The solvated compounds of acceptable salt and root of red-rooted salvia phenolic acid B, tanshinone IIA or its pharmaceutically acceptable salt, mapping are different on
Structure body, diastereoisomer, tautomer or its arbitrary proportion mixture, including racemic mixture；
It also include pharmaceutic adjuvant or other compatible drugs in the enhancing iPS characteristics of cell biology drug；
The pharmaceutic adjuvant refers to conventional pharmaceutical excipient, such as solvent, disintegrating agent, corrigent, preservative, colorant
With adhesive etc.；
The enhancing iPS characteristics of cell biology drug includes various clinical pharmaceutical dosage form, such as tablet, injection, rouge
Plastid nanoparticle, controlled release agent etc.；
The principle of the present invention: after nude mice is subcutaneously injected by appropriate iPS in the present invention, it is seen that iPS cell can break up three embryos
Then layer pre-processes iPS with the Salvia Miltiorrhiza Monomer ingredient of various concentration, observe the biology effect of the Salvia Miltiorrhiza Monomer ingredient of various concentration
It answers, the expression of OCT-4, C-myc after different Salvia Miltiorrhiza Monomer ingredients pretreatment iPS cells are detected by QPCR method, as a result table
Bright, root of red-rooted salvia phenolic acid B and tanshinone IIA sodium sulfonate can significantly improve the differentiation and proliferation ability of iPS, and root of red-rooted salvia phenolic acid B is in the party
The effect in face is more significant.
The present invention has the following advantages and effects with respect to the prior art:
(1) iPS is pre-processed by the Salvia Miltiorrhiza Monomer ingredient of various concentration in the present invention, compares the Salvia Miltiorrhiza Monomer of each concentration
Influence of the ingredient to the bioactivity of iPS, the results show that sodium tanshinon Ⅱa silate can promote multipotency to induce with root of red-rooted salvia phenolic acid B
Stem cells hyperplasia；Wherein, root of red-rooted salvia phenolic acid B can promote the proliferation of the iPS cell of in vitro culture, reduce its apoptosis, and can improve
The expression of stem cell multi-lineage potential related gene (Oct4 and c-myc gene), to improve iPS cell differentiation.
(2) the present invention provides a kind of enhancing iPS characteristics of cell biology drug, which can promote in vitro culture
The proliferation of iPS cell reduces its apoptosis, improves iPS cell differentiation, can be used for treating the nervous system disease, angiocarpy
The human diseases such as disease (such as ischemic heart disease, atherosclerosis, hypertension), reproductive disease.
Detailed description of the invention
Fig. 1 is the aspect graph of iPS cell colony；Wherein, A: the iPS cell colony (40 normally cultivated under optical microscopy
×)；B: the normal iPS cell colony (40 ×) under fluorescence microscope；C: the iPS cellular morphology (40 ×) of differentiation.
Fig. 2 is the aspect graph of embryoid body；Wherein, A: the embryoid body (40 ×) under optical microscopy；B；Under fluorescence microscope
Embryoid body (40 ×).
Fig. 3 is the aspect graph after three embryonic tissue HE dyeing in teratoma；Wherein, A: the cilium column of endoderm origin
Columnar epithelium；B: the chrysanthemum in ectodermal histological source rolls into a ball the original nerve channel of sample；C: the cartilage islands in mesoderm tissues source.
Fig. 4 is the time growth curve figure of sodium tanshinon Ⅱa silate pretreatment iPS cell.
Fig. 5 is the time growth curve figure after tanshinone IIA pretreatment iPS cell.
Fig. 6 is the time growth curve figure after root of red-rooted salvia phenolic acid B pretreatment iPS cell.
Fig. 7 is OCT-4, C-myc gene expression results analysis chart after root of red-rooted salvia phenolic acid B pretreatment iPS cell.
Specific embodiment
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
In the embodiment of the present invention, raw material Radix Salviae Miltiorrhizae is that Ke Fei Pharmaceuticals Ltd in Nanjing gifts, and other reagents are commercially available
Reagent, analysis is pure, does not purify；The differentiation situation of dyeing detection iPS is dyed using HE；Western blot method detection OCT-4,
The expression of C-myc；
Embodiment 1 prepares iPS cell
(1) preparation of trophoderm (MEF): T25 culture bottle is added in the gelatin of 0.1% (volume fraction), shakes up covering,
It is absorbed after 37 DEG C of cell incubators stand 20min, the MEF culture solution that 5~6mL preheats 37 DEG C is added, at the same time will
Mouse embryonic fibroblasts (being purchased from Shanghai Chinese Academy of Sciences cell bank) are quickly removed from liquid nitrogen, are placed in 37 DEG C of water-baths and are quickly melted
It is taken in super-clean bench after solution and the alcohol wipe cryopreservation tube for being immediately 75% with volume fraction, the cell suspension in cryopreservation tube is turned
It moves in the 15mL centrifuge tube of the culture solution containing MEF, 5min is centrifuged with 1000rpm, abandon after supernatant is resuspended and be added to T25 culture bottle
In, it is placed into CO2In constant incubator, culture obtains trophoderm afterwards for 24 hours can be added iPS cell；
(2) culture and passage of iPS cell: cultivating the trophoderm obtained afterwards for 24 hours in step (1), can under 4 power microscopes
See and be uniformly paved with T25 culture bottle, it is (raw purchased from Chinese Academy of Sciences Shanghai Sheng Ke institute that iPS cell can be removed from liquid nitrogen rapidly at this time
Change cell institute and OEG cell institute, Chinese Academy of Sciences Shanghai Sheng Ke institute stem cell platform) cryopreservation tube, resuscitation process similar to mice embryonic at
The T25 culture bottle of the directly incoming MEF bed board of the iPS cell of recovery is placed in 37 DEG C of cell incubators, changed daily by fibrocyte
Liquid and the variation (Fig. 1) for observing cell colony form.It grows to suitable size to cell colony to pass in time, PBS (not calcium-magnesium-containing
Ion) gently rinse one time after 0.25% (volume fraction) pancreatin (contain EDTA) digestion is added, mouse iPS cell culture fluid terminates
Digestion is centrifuged 5min with 1000rpm, resets and add culture solution piping and druming in abandoning and is prepared into single cell suspension.
Embodiment 2 prepares Salvia Miltiorrhiza Monomer ingredient
(1) it uses volume fraction to extract Radix Salviae Miltiorrhizae (1kg) for 95% ethyl alcohol, obtains total extract 76g；Total extract is suspended in
It in 500mL water, is extracted twice with hexamethylene 100mL, discards hexamethylene layer.Then it is extracted twice with ethyl acetate 100mL, with rotation
Turn evaporation under reduced pressure concentration, obtains Ethyl acetate fraction；Further ethyl acetate is extracted with the method for silica gel column chromatography
Position is separated, and using cyclohexane-ethyl acetate gradient elution, is collected cyclohexane-ethyl acetate 20:1 and is eluted position, decompression
Monomeric compound tanshinone IIA (1.1g) is obtained after concentration, cyclohexane-ethyl acetate 2:1 is collected and elutes position, after reduced pressure
It obtains monomeric compound root of red-rooted salvia phenolic acid B (1.3g), and identifies the molecular structure of monomeric compound with method of spectroscopy.
Tanshinone IIA: C19H18O3, LSIMS, m/z=295 [M+H]+；1H-NMR(CDCl3, 300MHz): δ=1.31
(6H,s,H3-18and H3-18A),1.66(2H,m,H2-3),1.81(2H,m,H2-2),2.26(3H,s,H3-17),3.29
(2H, t, J=6.6Hz, H2- 1), 7.22 (1H, s, H-16), 7.55 (1H, d, J=8.3Hz, H-6), 7.63 (1H, d, J=
8.3Hz, H-5) by the above spectral data and and standard control, it can be determined that the compound be tanshinone IIA, structure is such as
Shown in formula III:
Root of red-rooted salvia phenolic acid B: C36H30O16, ESIMS, m/z=717 [M-H]-；1H-NMR(DMSO-d6, 300MHz): δ=2.96,
2.76(4H,m,H2-7and H2- 7a '), 4.29 (1H, d, J=5.1Hz, H-8a), 5.11 (2H, m, H-8 ' and H-8a '),
5.80 (1H, d, J=5.1Hz, H-7a), 6.13 (1H, d, J=15.9Hz, H-8), 6.24 (1H, dd, J=1.8,8.1Hz, H-
6a), 6.45 (1H, d, J=1.8Hz, H-2a), 6.48 (1H, d, J=8.1Hz, H-5a), 6.54-6.72 (6H, m, H-2 ', H-
5 ', H-6 ', H-2a ', H-5a ', H-6a '), 6.77 (1H, d, J=8.4Hz, H-5), 7.08 (1H, d, J=8.4Hz, H-6),
7.44 (1H, d, J=15.9Hz, H-7) by the above spectral data and and standard control, it can be determined that the compound be pellet
Join phenolic acid B (shown in formula I).
(2) synthesis of sodium tanshinon Ⅱa silate
0.523g tanshinone IIA, 25mL glacial acetic acid, 40mL acetic anhydride are placed in there-necked flask, under the stirring of side, while being gradually added into
The 20mL concentrated sulfuric acid-glacial acetic acid (1:1V/V) mixed liquor, temperature are controlled at 10~15 DEG C, and 2h is stirred at room temperature after being added dropwise.It will
The mixture of reaction is slowly injected into isometric cold water, places 3 hours, 20mL sodium chloride saturated solution is added after filtering,
Filter to obtain red precipitate.It is suspended in water, then removes unreacted tanshinone IIA with chloroform extraction, be evaporated, use first
Alcohol recrystallization is secondary, obtains red acicular crystal, surveys 193~195 DEG C of fusing point after well-dried, yield 79%.Synthesize road
Line is as follows:
Sodium tanshinon Ⅱa silate is red acicular crystal (methanol), and vanilla-concentrated sulfuric acid colour developing is orange-yellow.ESI-MS m/
z:373.0[M-Na]-。1H-NMR(CD3OD, 300MHz): δ=1.32 (6H, s, H3-18and H3-18A),1.68(2H,m,H2-
3),1.80(2H,m,H2-2),2.46(3H,s,H3- 17), 3.16 (2H, t, J=6.3Hz, H2- 1), 7.71 (1H, d, J=
8.1Hz, H-6), 7.79 (1H, d, J=8.1Hz, H-5) by the above spectral data and and standard control, it can be determined that should
Compound is sodium tanshinon Ⅱa silate (shown in formula II).
Embodiment 3 prepares embryoid body
The culture dish for selecting 8cm (is implemented after being covered overturning in the iPS cell hanging drop that its inner face drips upper 4~6 200 μ L
Example 1 is prepared), 1mL PBS is added in culture dish, then lightly overturns lid.CO2It cultivates 2~3 days, sees in constant incubator
Cell mass is observed, is drawn in the incoming pretreated T25 culture bottle of agar with dropper and carries out culture 4~5 days, obtain embryoid body；It is quasi-
The formation of idiosome demonstrates iPS cell with Multidirectional Differentiation ability (Fig. 2).
Embodiment 4 prepares iPS differentiation model
IPS single cell clone strain (embodiment 1 is prepared) is centrifuged after amplification digestion, is counted under microscope, take 1 ×
105Cell melt and be prepared into cell suspension in the PBS buffer solution of 200 μ L；The cell suspension inoculation is big by 4 weeks
BALB/c nude mice (being purchased from Guangdong Medical Lab Animal Center) oxter is subcutaneous, observes the growing state of teratoma, after 4~5 weeks,
Excessive amobarbital, which is injected into after nude mice abdominal cavity is put to death, takes out teratoma, the paraformaldehyde that mass fraction is 4% on super-clean bench
Specimens paraffin embedding slices carry out HE dyeing observation after fixation, as a result see Fig. 3, it is seen that iPS cell can break up three germinal layers.
Comparison of the 5 different monomers ingredient of embodiment to the iPS influence being proliferated
The iPS cell (embodiment 1 is prepared) of logarithmic growth phase, with 1 × 106/ mL cell density is inoculated in 96 holes
Plate, every 100 μ L of hole；It after cell is adherent, inhales and abandons liquid in hole, the tanshinone IIA of various concentration is added by every 100 μ L of hole
(0.15625,0.3125,0.625,1.25,2.5,5,10 μ g/mL, embodiment 2 are prepared), sodium tanshinon Ⅱa silate (1.5
×10-4、1.5×10-3、1.5×10-2、1.5×10-1, 1.5,15,150 μm of ol/L, embodiment 2 is prepared), root of red-rooted salvia phenolic acid B
Group (1 × 10-4、5×10-5、2.5×10-5、1.25×10-5、6.25×10-6、3.125×10-6、1.5625×10-6Mol/L,
Embodiment 2 is prepared) and blank control group be only added iPS cell culture fluid, every group 8 are parallel.Respectively processing (4,8,
12,24,48h) after, it is protected from light and CCK-8 (Japanese colleague's chemistry institute) 10 hole μ L/ is added, place 2h in incubator, existed with microplate reader
450nm measures each hole OD value D (450).As a result see Fig. 4~6.As a result illustrate that root of red-rooted salvia phenolic acid B and sodium tanshinon Ⅱa silate can
To promote the proliferation of iPS cell, its apoptosis is reduced, the optimization process concentration of root of red-rooted salvia phenolic acid B is 2.5 × 10-5Mol/L, tanshinone
The effective concentration of II A sodium sulfonate is preferably 150 μm of ol/L.
Influence of the 6 Salvia Miltiorrhiza Monomer ingredient of embodiment to iPS differentiation potential gene OCT-4 and C-myc
Grouping: by 1 × 106A iPS cell (embodiment 1 is prepared) is planted to be reached into 2 days cell densities of 6cm culture dish culture
85~90%, cell non-serum culture synchronizes 6~12h, is randomly divided into 3 groups, it may be assumed that 1. Normal group；2. root of red-rooted salvia phenolic acid B group
(final concentration 2.5 × 10-5mol/L)；Sodium tanshinon Ⅱa silate 3. (150 μm of ol/L) group；Each group is adopted after drug culture 48h is added
OCT-4 and C-myc, which is detected, with QPCR method expresses the (OCT-4:AGGATGTGGTTCGAGTATGGTT of primer 5 ' -3 '；3'-5'
AAGGGACTGAGTAGAGTGTGGTG；C-myc:5'-3'GGAAACGACGAGAACAGTTG；3'-5'
GCCAAGGTTGTGAGGTTAGG).As a result (Fig. 7) show root of red-rooted salvia phenolic acid B compared with sodium tanshinon Ⅱa silate significantly improve OCT-4 and
The expression of C-myc significantly increases the differentiation capability of iPS.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (7)
1. a kind of application of Salvia Miltiorrhiza Monomer compound in preparation enhancing iPS characteristics of cell biology drug, it is characterised in that: institute
The Salvia Miltiorrhiza Monomer compound stated be at least one of root of red-rooted salvia phenolic acid B and tanshinone IIA sodium sulfonate, the root of red-rooted salvia phenolic acid B and
The structural formula of tanshinone IIA is as shown in formula I and formula II:
The enhancing iPS characteristics of cell biology, which refers to, promotes iPS cell Proliferation, improves iPS cell differentiation.
2. Salvia Miltiorrhiza Monomer compound according to claim 1 answering in preparation enhancing iPS characteristics of cell biology drug
With, it is characterised in that:
The effective concentration of the root of red-rooted salvia phenolic acid B is 2.5 × 10-5mol/L；
The effective concentration of the sodium tanshinon Ⅱa silate is 150 μm of ol/L.
3. Salvia Miltiorrhiza Monomer compound according to claim 1 or 2 is in preparation enhancing iPS characteristics of cell biology drug
Using, it is characterised in that:
The Salvia Miltiorrhiza Monomer compound is root of red-rooted salvia phenolic acid B.
4. Salvia Miltiorrhiza Monomer compound according to claim 1 answering in preparation enhancing iPS characteristics of cell biology drug
With, it is characterised in that:
The enhancing iPS characteristics of cell biology drug includes the described in any item root of red-rooted salvia phenolic acid B of claims 1 to 3, Radix Salviae Miltiorrhizae
The pharmaceutically acceptable salt of ketone IIA sodium sulfonate.
5. Salvia Miltiorrhiza Monomer compound according to claim 4 answering in preparation enhancing iPS characteristics of cell biology drug
With, it is characterised in that:
It also include pharmaceutic adjuvant or other compatible drugs in the enhancing iPS characteristics of cell biology drug.
6. Salvia Miltiorrhiza Monomer compound according to claim 5 answering in preparation enhancing iPS characteristics of cell biology drug
With, it is characterised in that:
The pharmaceutic adjuvant is solvent, disintegrating agent, corrigent, preservative, colorant or adhesive.
7. Salvia Miltiorrhiza Monomer compound according to any one of claim 4 to 6 enhances iPS characteristics of cell biology medicine in preparation
Application in object, it is characterised in that:
The enhancing iPS characteristics of cell biology drug is tablet, injection, liposome nano granule or controlled release agent.
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