CN108272806B - Jolkinolide B and derivative are used as the purposes of miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor - Google Patents
Jolkinolide B and derivative are used as the purposes of miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor Download PDFInfo
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- 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
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
Abstract
The invention discloses the purposes that jolkinolide B and derivative are used as miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor.Present invention discover that; jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl group jolkinolide B can significantly improve the expression of miR-21 in mesenchymal stem cell; and then promote mesenchymal stem cell Osteoblast Differentiation, miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor can be prepared into.It improves miR-21 expression or promotes the pharmaceutical preparation of mesenchymal stem cell Osteoblast Differentiation that can contain above compound or its pharmaceutical salts, and pharmaceutically acceptable carrier or excipient, pharmaceutically acceptable dosage form is made；Pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or Auxiliary Liquid Material；Pharmaceutically acceptable dosage form includes tablet, capsule, granule, injection, pill, syrup, powder, paste.
Description
Technical field
The invention belongs to biological fields, are related to miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor.
Background technique
In marrow in addition to containing candidate stem cell of the energy differentiation and development at various haemocytes, also containing the non-hematopoiesis group of generation
The mescenchymal stem cell (MSCs) knitted, because it is easier adherent and forms fibroblast-like clone, therefore the document having also
MSCs is referred to as attached cell or fibroblastic colony units-forming.Due to their support structures from marrow, and can
Using the growth as trophoderm hematopoiesis support stem cell, therefore also, someone is called marrow stromal cell (BMSCs).In view of
The following characteristics of BMSCs and increasingly arouse people's interest: 1, under the induction of different physicochemical environment and cell factor,
BMSCs divides with that can be divided into the polyphylys such as osteoblast, cartilage cell, fat cell, muscle cell even neuron cell
Change potential；2, BMSCs is hematopoiesis support cell, the growth as trophoderm hematopoiesis support stem cell.Due to easily separated, expansion
The features such as increasing and in vitro operation are easy, mesenchymal stem cell is in the fields such as organizational project, cell transplantation application prospect ten
Divide wide.
Osteoporosis is a kind of so that bone amount reduction, bone micro-structure destroy, bone brittleness increases and easily complete characterized by fracture
Body metabolic bone disease.Glucocorticoid-induced osteoporosis is the main Types of secondary osteoporosis, is prevented and treated
It is field of orthopaedics serious problems urgently to be resolved.The decline of mesenchymal stem cell Osteoblast Differentiation ability occurs with osteoporosis
It is closely related.Some researches show that miR-21 is related to mesenchymal stem cell Osteoblast Differentiation, and the high expression of miR-21 can promote
Mesenchymal stem cell Osteoblast Differentiation (bibliography: miR-21 regulates and controls the research of human marrow mesenchymal stem cell Osteoblast Differentiation,
Tooth body dental pulp Periodontology, 8 phases of volume 25 in 2015).
Diterpene-kind compound is divided into Cesong alkyl type diterpine, Diterpene, Ah replacing according to the difference of chemical structure parent nucleus
This alkane type diterpene, Kaurane diterpine etc..Different types of diterpene, same type different chemical structures diterpene due to chemistry
The difference of parent nucleus, substituent group in structure, pharmacological activity is varied, becomes the precious resources library of drug development.
Summary of the invention
It is an object of that present invention to provide miR-21 activator, which, which can be used as, promotes medulla mesenchyma dry
Osteoporosis is alleviated or treated to the promotor of cell Osteoblast Differentiation for promoting mesenchymal stem cell Osteoblast Differentiation, and then
Disease.
Above-mentioned purpose is achieved through the following technical solutions:
Wartwort lactone A and B, Euphorangin C and D, jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl
Base jolkinolide B, jolkinolide A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime are diterpene compound, but parent nucleus and
Substituent group is different, and chemical information is as shown in the table.
Wartwort lactone A and B are used as miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor
Wartwort lactone A or B are used to prepare the purposes of miR-21 activator.
A kind of pharmaceutical preparation improving miR-21 expression, containing wartwort lactone A or B or its pharmaceutical salts, and pharmaceutically can be with
The carrier or excipient of receiving, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Powder, syrup, paste.
Wartwort lactone A or B are used to prepare the purposes of mesenchymal stem cell Osteoblast Differentiation promotor.
A kind of pharmaceutical preparation promoting mesenchymal stem cell Osteoblast Differentiation, containing wartwort lactone A or B or its is medicinal
Salt, and pharmaceutically acceptable carrier or excipient, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Syrup, powder, paste.
Euphorangin C and D are used as miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor
Euphorangin C or D are used to prepare the purposes of miR-21 activator.
A kind of pharmaceutical preparation improving miR-21 expression, containing Euphorangin C or D or its pharmaceutical salts, and pharmaceutically
Pharmaceutically acceptable dosage form is made in acceptable carrier or excipient.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Powder, syrup, paste.
Euphorangin C or D are used to prepare the purposes of mesenchymal stem cell Osteoblast Differentiation promotor.
It is a kind of promote mesenchymal stem cell Osteoblast Differentiation pharmaceutical preparation, containing Euphorangin C or D or its
Pharmaceutical salts, and pharmaceutically acceptable carrier or excipient, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Syrup, powder, paste.
Jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl group jolkinolide B is used as miR-21 activator
And mesenchymal stem cell Osteoblast Differentiation promotor
Jolkinolide B, 17- hydroxyl jolkinolide B or 17- acetyl group jolkinolide B is used to prepare miR-21 and swashs
The purposes of agent living.
A kind of pharmaceutical preparation improving miR-21 expression, contains jolkinolide B, 17- hydroxyl jolkinolide B or 17-
Acetyl group jolkinolide B or its pharmaceutical salts, and pharmaceutically acceptable carrier or excipient, being made can pharmaceutically connect
The dosage form received.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Powder, syrup, paste.
Jolkinolide B, 17- hydroxyl jolkinolide B or 17- acetyl group jolkinolide B fills between being used to prepare marrow
The purposes of matter stem cell Osteoblast Differentiation promotor.
A kind of pharmaceutical preparation promoting mesenchymal stem cell Osteoblast Differentiation, contains jolkinolide B, 17- hydroxyl rock
Root of Beijing euphorbia lactone B or 17- acetyl group jolkinolide B or its pharmaceutical salts, and pharmaceutically acceptable carrier or excipient, system
At pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Syrup, powder, paste.
Jolkinolide A is used as miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor
Jolkinolide A is used to prepare the purposes of miR-21 activator.
A kind of pharmaceutical preparation improving miR-21 expression, containing jolkinolide A or its pharmaceutical salts, and pharmaceutically can be with
The carrier or excipient of receiving, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Powder, syrup, paste.
Jolkinolide A is used to prepare the purposes of mesenchymal stem cell Osteoblast Differentiation promotor.
A kind of pharmaceutical preparation promoting mesenchymal stem cell Osteoblast Differentiation, containing jolkinolide A or its is medicinal
Salt, and pharmaceutically acceptable carrier or excipient, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Syrup, powder, paste.
Euphorbia ebiacteolata Hayata A prime is used as miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor
Euphorbia ebiacteolata Hayata A prime is used to prepare the purposes of miR-21 activator.
A kind of pharmaceutical preparation improving miR-21 expression, containing euphorbia ebiacteolata Hayata A prime or its pharmaceutical salts, and pharmaceutically can be with
The carrier or excipient of receiving, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Powder, syrup, paste.
Euphorbia ebiacteolata Hayata A prime is used to prepare the purposes of mesenchymal stem cell Osteoblast Differentiation promotor.
A kind of pharmaceutical preparation promoting mesenchymal stem cell Osteoblast Differentiation, containing euphorbia ebiacteolata Hayata A prime or its is medicinal
Salt, and pharmaceutically acceptable carrier or excipient, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Syrup, powder, paste.
Euphorbia ebiacteolata Hayata B prime is used as miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor
Euphorbia ebiacteolata Hayata B prime is used to prepare the purposes of miR-21 activator.
A kind of pharmaceutical preparation improving miR-21 expression, containing euphorbia ebiacteolata Hayata B prime or its pharmaceutical salts, and pharmaceutically can be with
The carrier or excipient of receiving, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Powder, syrup, paste.
Euphorbia ebiacteolata Hayata B prime is used to prepare the purposes of mesenchymal stem cell Osteoblast Differentiation promotor.
A kind of pharmaceutical preparation promoting mesenchymal stem cell Osteoblast Differentiation, containing euphorbia ebiacteolata Hayata B prime or its is medicinal
Salt, and pharmaceutically acceptable carrier or excipient, are made pharmaceutically acceptable dosage form.
Further, the corresponding acid of the pharmaceutical salts includes hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, tartaric acid, methanesulfonic acid, amber
Amber acid, fumaric acid, citric acid, malic acid or maleic acid etc..
Further, the pharmaceutically acceptable carrier or excipient include one or more solids, semisolid or liquid
Body auxiliary material.
Further, the pharmaceutically acceptable dosage form include tablet, capsule, granule, injection, pill,
Syrup, powder, paste.
Wartwort lactone A and B, Euphorangin C and D, jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl
It is dry thin that base jolkinolide B, jolkinolide A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime can remarkably promote medulla mesenchyma
The expression of miR-21 in born of the same parents, and then promote mesenchymal stem cell Osteoblast Differentiation.
Detailed description of the invention
Fig. 1 is influence of the wartwort lactone A and B to mesenchymal stem cell Osteoblast Differentiation and miR-21 relative expression quantity；
Fig. 2 is shadow of the Euphorangin C and D to mesenchymal stem cell Osteoblast Differentiation and miR-21 relative expression quantity
It rings；
Fig. 3 is jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl group jolkinolide B to medulla mesenchyma
The influence of stem cell Osteoblast Differentiation and miR-21 relative expression quantity；
Fig. 4 is influence of the jolkinolide A to mesenchymal stem cell Osteoblast Differentiation and miR-21 relative expression quantity；
Fig. 5 is influence of the euphorbia ebiacteolata Hayata A prime to mesenchymal stem cell Osteoblast Differentiation and miR-21 relative expression quantity；
Fig. 6 is influence of the euphorbia ebiacteolata Hayata B prime to mesenchymal stem cell Osteoblast Differentiation and miR-21 relative expression quantity.
Specific embodiment
Technical solution of the present invention is introduced combined with specific embodiments below.Non- special emphasis tests material in following embodiments
Material is routine experiment material, is had no special requirements, and is all the conventional material that those skilled in the art are easy to get.
One, experimental material
Wartwort lactone A and B, Euphorangin C and D, jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl
Base jolkinolide B, jolkinolide A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime purchase or self-control, purity 95% with
On.SPF grades of SD rats, male and female are regardless of, and Jiangning county Qinglongshan animal reproduction field is purchased from.
DMEM/F12, fetal calf serum are purchased from Hyclone company.SD rat bone marrow mesenchymal stem cells osteogenic induction culture
Base, alizarin red dye liquor are purchased from match industry (Guangzhou) Biotechnology Co., Ltd.PrimeScrip RT Master Mix (reverse transcription examination
Agent box), SYBR Premix Ex Taq (PCR kit for fluorescence quantitative) be purchased from Dalian treasured biotech firm.
β-actin, miR-21 primer are synthesized by Sangon Biotech (Shanghai) Co., Ltd., and sequence is as follows.
Two, experimental method
1, the separation and culture of rat BMSCs
Vertebra dislocation method puts to death SD rat and aseptically removes shin bone and femur, rejects flesh attached thereto
Meat, ligament and articular cartilage, cut off the metaphysis exposure ossis of two sides, are containing volume fraction with the extraction of 10mL asepsis injector
The DMEM/F12 culture medium repeated flushing ossis of 10% fetal calf serum.Flushing liquor is transferred to 25cm again2In culture bottle, it is placed in
37 DEG C, volume fraction 5%CO2Cell incubator in culture.Culture medium is replaced after 48h for the first time, replaces and trains every 1d later
Support base.When cell fusion degree reaches 80%, passed on after the digestion of 0.25% pancreatin in the ratio of 1:3.According to the above method by cell
Culture is to the 3rd generation, to carry out subsequent experimental.
2, experimental group and processing method
Take culture to the 3rd generation BMSCs of logarithmic phase, adjustment cell concentration is 2 × 108/ L, is inoculated in 6 orifice plates, every hole
1mL cell suspension, then plus 1mL complete medium, when cell fusion degree reaches about 80%, as follows be grouped, handle:
Control group: fresh DMEM/F12 complete medium (normal incubation medium) is replaced, continues to cultivate；
Positive group: replacement SD rat bone marrow mesenchymal stem cells Osteogenic Induction Medium (induced medium) continues to cultivate；
Administration group: on the basis of the control group, being separately added into low concentration (10 μM), high concentration (20 μM) wartwort lactone A or B,
Or Euphorangin C or D or jolkinolide B, 17- hydroxyl jolkinolide B or 17- acetyl group jolkinolide B, or
Jolkinolide A or euphorbia ebiacteolata Hayata A prime or euphorbia ebiacteolata Hayata B prime, continue to cultivate.
Every 3d is changed liquid 1 time, continues to cultivate 11d.
3, alizarin red agent dyeing detection Osteoblast Differentiation rate
Culture medium is discarded, is washed 3 times with 4 DEG C of pre-cooling PBS, 40g/L paraformaldehyde fixes 15min at room temperature, discards poly
Formaldehyde, PBS are washed 3 times, Alizarin red staining 15min, discard dye liquor, and distilled water is washed 2 times, finally observed under the microscope, calculate phase
Mesenchymal stem cell Osteoblast Differentiation index is used as to calcium knuckle area (%).
4, the relative expression quantity of RT-qPCR method detection miR-21
Cell uses PrimeScrip after measuring concentration by Trizol extraction cell total rna is added after experimental group processing
RT Master Mix (reverse transcription reagent box) uses SYBR according to the system reverse transcription of 500ng/10 μ l at the cDNA of 50 μ l
Premix Ex Taq (PCR kit for fluorescence quantitative) is detected on ABI7500 real-time fluorescence quantitative PCR instrument with 20 μ l systems
MiR-21 relative expression quantity.It uses β-actin gene expression dose as internal reference, calculates the ratio generation of miR-21/ β-actin gene
The relative expression levels of table miR-21, gene expression relative quantification, which is calculated, carries software using instrument.
5, statistical analysis
Data processing carries out one-way analysis of variance, comparison among groups LSD method, as a result with equal using 19.0 software of SPSS
Number ± standard deviation indicates that P < 0.05 thinks there is statistical difference.
Three, experimental result
1, wartwort lactone A and B, Euphorangin C and D, jolkinolide B, 17- hydroxyl jolkinolide B and 17- second
Acyl group jolkinolide B, jolkinolide A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime are to mesenchymal stem cell skeletonization point
The influence of change
Compared with the control group, the Osteoblast Differentiation rate of positive group mesenchymal stem cell significantly increases (P < 0.05)；With it is right
It is compared according to group, the Osteoblast Differentiation rate of each administration group mesenchymal stem cell significantly increases (P < 0.05), and is in dose-dependant
Property.
As a result as shown in table 1 and Fig. 1-6.
1 each group mesenchymal stem cell Osteoblast Differentiation of table compares (n=3)
| Group | Calcium knuckle area (%) | Group | Calcium knuckle area (%) |
| Control group | 4.58±1.74 | Jolkinolide B- high concentration | 34.69±3.99 |
| Positive group | 17.21±3.52 | 17- hydroxyl jolkinolide B- low concentration | 24.08±3.28 |
| Wartwort lactone A- low concentration | 22.38±3.04 | 17- hydroxyl jolkinolide B- high concentration | 35.80±4.09 |
| Wartwort lactone A- high concentration | 34.65±3.57 | 17- acetyl group jolkinolide B- low concentration | 25.25±3.14 |
| Wartwort lactone B- low concentration | 21.90±3.42 | 17- acetyl group jolkinolide B- high concentration | 37.13±3.53 |
| Wartwort lactone B- high concentration | 33.41±3.95 | Jolkinolide A- low concentration | 28.13±3.61 |
| EuphoranginC- low concentration | 25.35±4.03 | Jolkinolide A- high concentration | 41.04±4.38 |
| EuphoranginC- high concentration | 37.05±3.86 | Euphorbia ebiacteolata Hayata A prime-low concentration | 30.05±3.77 |
| EuphoranginD- low concentration | 27.12±3.75 | Euphorbia ebiacteolata Hayata A prime-high concentration | 43.29±3.90 |
| EuphoranginD- high concentration | 39.42±4.14 | Euphorbia ebiacteolata Hayata B prime-low concentration | 27.12±3.08 |
| Jolkinolide B- low concentration | 23.34±3.62 | Euphorbia ebiacteolata Hayata B prime-high concentration | 40.24±4.29 |
2, wartwort lactone A and B, Euphorangin C and D, jolkinolide B, 17- hydroxyl jolkinolide B and 17- second
Acyl group jolkinolide B, jolkinolide A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime are to miR- in mesenchymal stem cell
The influence of 21 relative expression quantities
Compared with the control group, miR-21 relative expression quantity significantly increases (P < in positive group mesenchymal stem cell
0.05)；Compared with the control group, miR-21 relative expression quantity significantly increases (P < in each administration group mesenchymal stem cell
It 0.05), and is in dose dependent.As a result as shown in table 2 and Fig. 1-6.
2 each group mesenchymal stem cell Osteoblast Differentiation rate (n=3) of table
| Group | Relative expression quantity | Group | Relative expression quantity |
| Control group | 1.00±0.09 | Jolkinolide B- high concentration | 4.29±0.35 |
| Positive group | 2.84±0.25 | 17- hydroxyl jolkinolide B- low concentration | 3.22±0.30 |
| Wartwort lactone A- low concentration | 3.14±0.31 | 17- hydroxyl jolkinolide B- high concentration | 4.37±0.29 |
| Wartwort lactone A- high concentration | 4.35±0.38 | 17- acetyl group jolkinolide B- low concentration | 3.17±0.27 |
| Wartwort lactone B- low concentration | 3.21±0.29 | 17- acetyl group jolkinolide B- high concentration | 4.41±0.34 |
| Wartwort lactone B- high concentration | 4.32±0.35 | Jolkinolide A- low concentration | 3.73±0.25 |
| EuphoranginC- low concentration | 3.19±0.31 | Jolkinolide A- high concentration | 4.89±0.28 |
| EuphoranginC- high concentration | 4.28±0.36 | Euphorbia ebiacteolata Hayata A prime-low concentration | 3.65±0.34 |
| EuphoranginD- low concentration | 3.43±0.28 | Euphorbia ebiacteolata Hayata A prime-high concentration | 4.96±0.37 |
| EuphoranginD- high concentration | 4.49±0.29 | Euphorbia ebiacteolata Hayata B prime-low concentration | 3.78±0.29 |
| Jolkinolide B- low concentration | 3.05±0.32 | Euphorbia ebiacteolata Hayata B prime-high concentration | 4.99±0.32 |
The above results show wartwort lactone A and B, Euphorangin C and D, jolkinolide B, the 17- hydroxyl rock root of Beijing euphorbia
Lactone B and 17- acetyl group jolkinolide B, jolkinolide A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime can significantly improve
The expression of miR-21 in mesenchymal stem cell, and then promote mesenchymal stem cell Osteoblast Differentiation.Wartwort lactone A and B,
Euphorangin C and D, jolkinolide B, 17- hydroxyl jolkinolide B and 17- acetyl group jolkinolide B, the rock root of Beijing euphorbia
Lactone A, euphorbia ebiacteolata Hayata A prime, euphorbia ebiacteolata Hayata B prime can be prepared into miR-21 activator and mesenchymal stem cell skeletonization point
Change promotor.It activates miR-21 expression or promotes the pharmaceutical preparation of mesenchymal stem cell Osteoblast Differentiation can be containing in wartwort
In ester A or B or Euphorangin C or D or jolkinolide B, the 17- hydroxyl jolkinolide B or 17- acetyl basement rock root of Beijing euphorbia
Ester B or jolkinolide A or euphorbia ebiacteolata Hayata A prime or euphorbia ebiacteolata Hayata B prime or its pharmaceutical salts, and pharmaceutically acceptable
Pharmaceutically acceptable dosage form is made in carrier or excipient；The corresponding acid of the pharmaceutical salts include hydrochloric acid, hydrobromic acid, phosphoric acid,
Sulfuric acid, tartaric acid, methanesulfonic acid, succinic acid, fumaric acid, citric acid, malic acid or maleic acid etc.；The pharmaceutically acceptable
Carrier or excipient include one or more solids, semisolid or Auxiliary Liquid Material；The pharmaceutically acceptable dosage form includes
Tablet, capsule, granule, injection, pill, syrup, powder, paste.
The above-mentioned technical solution that the specific embodiments are only for explaining the present invention, it will be appreciated by those skilled in the art that, this hair
Bright protection scope is not limited to above-mentioned specific embodiment.
Claims (1)
1. jolkinolide B, 17- hydroxyl jolkinolide B or 17- acetyl group jolkinolide B is used to prepare medulla mesenchyma
The purposes of stem cell Osteoblast Differentiation promotor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810205736.0A CN108272806B (en) | 2018-03-13 | 2018-03-13 | Jolkinolide B and derivative are used as the purposes of miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor |
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| CN201810205736.0A CN108272806B (en) | 2018-03-13 | 2018-03-13 | Jolkinolide B and derivative are used as the purposes of miR-21 activator and mesenchymal stem cell Osteoblast Differentiation promotor |
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| Publication Number | Publication Date |
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| CN108272806A CN108272806A (en) | 2018-07-13 |
| CN108272806B true CN108272806B (en) | 2019-02-05 |
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