CN103989694A - Application of myricetrin for preventing and treating osteoporosis - Google Patents
Application of myricetrin for preventing and treating osteoporosis Download PDFInfo
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Abstract
The invention discloses an application of myricetrin for preventing and treating osteoporosis. Myricetrin is free from toxic effect on human mesenchymal stem cells, does not affect cell proliferation, has a protective effect on apoptosis of the human mesenchymal stem cells caused by H2O2, improves the oxidative stress state induced by H2O2 in the differentiation process, has a protective effect on ossifying differential inhibition of human bone mesenchymal stem cells caused by H2O2, has an inhibiting effect on enhancement of adipogenic differentiation of human bone mesenchymal stem cells caused by H2O2, and can inhibit expression of bone absorption factors so as to improve apoptosis and differential inhibition of the human mesenchymal stem cells and indirectly inhibit osteoclast activation to protect osteoporosis. In an osteoporotic model of a castrated mouse, the myricetrin can improve the oxidative stress state in serum and improve the bone micro-structures of the cancellous bone at the distal femur and the fourth lumbar vertebra, so that the myricetrin can improve the bone micro-structure by inhibiting oxidative stress and exerting the effect of preventing and treating osteoporosis.
Description
Technical field
The invention belongs to osteoporotic Prevention Technique field, relate to myricetrin and prevent and treat osteoporotic application.
Background technology
Osteoporosis (osteoporosis, OP) be the osseous tissue bone loss being caused by Different types of etiopathogenises, general, degeneration, the metabolic bone disease that bone micro-structure worsens and biomechanical property goes down, cause bone fragility to increase, easily fracture, the physical and mental health of middle-aged and elderly people in serious threat.
Oxidative stress (oxidative stress) is that in body, high activity material, as ROS (Reactive oxygen species) produces too much, has exceeded the removing ability of body, causes the unbalance a kind of state of oxidative and anti-oxidative.ROS in physiological range is regulating the normal function of human body to play an important role as aspects such as apoptosis, gene expression, signal transductions.Yet the ROS of high concentration can cause nucleic acid, protein, lipid to produce oxidation reaction, the 26S Proteasome Structure and Function of infringement cell, causes the generation of disease.
In recent years, research finds that oxidative stress plays an important role in osteoporosis develops.The generation of excess of oxygen free radical (ROS) can suppress bone marrow stroma stem cell (MSCs) Osteoblast Differentiation, cause MSCs and osteoblast (OB) apoptosis, promote osteoclast (OC) activation and increased functionality, cause bone resorption and bone formation unbalance, cause that bone micro-structure changes and bone amount reduces.
Myricetrin (myricitrin) is a kind of plant flavone glycosides, and rich content in the branch of Fructus Myricae rubrae, skin also contains this composition in other various fruits and plant.Abundant in view of its source, myricetrin ratio is easier to be extracted and purification.Due to the excellent activity of myricetrin, it is used as the important supplement of functional food, cosmetics and medicine.Lot of documents shows, myricetrin has the performances such as antiinflammatory, neuroprotective and antioxidation.
Summary of the invention
The object of the invention is to provide myricetrin to prevent and treat osteoporotic application.
For achieving the above object, the present invention has adopted following technical scheme:
Myricetrin is in the application for the preparation of in the osteoporotic medicine of control.
Contain the plant extract of myricetrin in the application for the preparation of in the osteoporotic medicine of control.
Myricetrin is in the application for the preparation of improving in the medicine of human marrow mesenchymal stem cell oxidative stress status.
The application of myricetrin in the medicine for the preparation of anti-human marrow mesenchyma stem cell apoptosis.
The application of myricetrin in the medicine suppressing for the preparation of anti-human marrow mesenchyma stem cell Osteoblast Differentiation.
The application of myricetrin in the medicine for the preparation of ALP activity in improving human marrow mesenchymal stem cell.
Myricetrin is in the application for the preparation of facilitating in improving human marrow mesenchymal stem cell in the medicine of bone differentiation gene Alp, Colla1 and Ocn expression.
Myricetrin is in the application for the preparation of suppressing in improving human marrow mesenchymal stem cell in the medicine of RANKL and IL-6 level.
The dosage of myricetrin is at least 5mg/kg.
Compared with prior art, the present invention has following useful technique effect:
Myricetrin is to human marrow mesenchymal stem cell (hBMSC) free of toxic effects, have protective effect to the apoptosis of hBMSC; And can improve oxidative stress status; HBMSC Osteoblast Differentiation is suppressed to have protective effect; To hBMSC, become fat differentiation to strengthen inhibited; Can suppress the expression of bone resorbing factor.In castration mouse model, myricetrin can improve the oxidative stress status in serum, improves the Grafting Cancellous Bone Bolt micro structure of distal femur and lumbar vertebra.
Human marrow mesenchymal stem cell is the more conventional cell model of the early stage skeletonization precursor growth of research, differentiation; myricetrin has protective effect to hBMSC; promoting bone growing; and by suppressing bone resorbing factor, suppress the activation of osteoclast; reduce bone resorption, finally play the osteoporotic effect of control.Ovariectomized mice model is bone rapping type after conventional menopause; by continuous lumbar injection, give and various dose myricetrin; obviously improve serum oxidative stress status, Grafting Cancellous Bone Bolt micro structure has been had to protective effect, shown the effect that it can be brought into play prevention and treat postmenopausal osteoporosis.
Myricetrin is pure natural substance, and medication is safer, and toxic and side effects is little.
Therefore, myricetrin can be applicable to osteoporotic control, is especially applied in the osteoporotic medicine of preparation control.
Accompanying drawing explanation
Fig. 1-1 is the impact of variable concentrations myricetrin on cell proliferation effect.
Fig. 1-2 is that myricetrin is to H
2o
2cause apoptotic protective effect.
Fig. 2 is that myricetrin can improve the testing result that cellular oxidation stress ROS level.
Fig. 3-1 is that myricetrin is at H
2o
2after effect, to the active effect of cell alkali phosphatase (ALP).
Fig. 3-2 are that myricetrin is at H
2o
2after effect, the effect to cellular matrix calcium deposition.
Fig. 3-3A, Fig. 3-3B, Fig. 3-3C are that myricetrin is at H
2o
2after effect, the impact on 3 kinds of (Alp, Colla1 and Ocn) Osteoblast Differentiation gene expression doses.
Fig. 4-1 is at H
2o
2after effect, the effect that myricetrin generates cytolipin.
Fig. 4-2 are at H
2o
2after effect, myricetrin is on becoming the impact of fat differentiation gene PPAR γ 2 expressions.
Fig. 5 A, Fig. 5 B are that myricetrin is at H
2o
2after effect, the impact on 2 kinds of bone resorbing factor IL-6 and RANKL expression.
Fig. 6-1A and Fig. 6-1B are the testing result that myricetrin can improve oxidative stress index MDA and GSH level in mice serum.
The Micro-CT result of OVX mouse femur far-end Grafting Cancellous Bone Bolt micro structure can be improved for myricetrin in Fig. 6-2.
The VG coloration result of OVX mouse femur far-end Grafting Cancellous Bone Bolt micro structure can be improved for myricetrin in Fig. 6-3.
The specific embodiment
Below in conjunction with drawings and Examples, the present invention is elaborated, the explanation of the invention is not limited.
HBMSC is human marrow mesenchymal stem cell, has multi-lineage potential, such as being divided into osteoblast, lipoblast, fibroblast etc., is the more conventional cell model of research growth of marrow mesenchyme stem cell, differentiation, hydrogen peroxide (H
2o
2) to process be also the external oxidative stress model of commonly using, for observing the impact of myricetrin on human marrow mesenchymal stem cell apoptosis and differentiation, and the effect of anti-oxidative damage, so select hBMSC as cell model, H
2o
2be treated to external oxidative stress model.Oophorectomize (castration) mouse model, as animal model, is the model of bone pine after the simulation postmenopausal women of commonly using.
1, myricetrin causes the protective effect of hBMSC apoptosis to oxidative stress
The toxic action of 1.1 simple myricetrins to cell
By hBMSC cell with 2 * 10
3individual/mL is inoculated on 96 orifice plates, after cell covers with, discard culture medium (composition: α-MEM culture fluid+20% hyclone (FBS)+1% dual anti-(mycillin)), add serum-free medium containing variable concentrations 0,0.1,1,10 μ M myricetrins to orifice plate, cultivate 24h and 72h, observe the impact of myricetrin on cell proliferation effect.At point of observation, utilize mtt assay to detect cytoactive.
As Figure 1-1, the myricetrin action time that abscissa is variable concentrations, the vertical coordinate of this figure is cell viability value to result, and the percent comparing with the OD value of blank group with the absorbance OD value of each group is explained.As seen from the figure, the myricetrin of variable concentrations is within observing time, to the propagation of cell and have no significant effect.
1.2 myricetrins cause the protective effect of hBMSC apoptosis to oxidative stress
Grouping situation: blank group; Simple H
2o
2processed group; 0.1 μ M Myricitrin+H
2o
2; 1 μ M Myricitrin+H
2o
2; 10 μ M Myricitrin+H
2o
2.
By hBMSC cell with 2 * 10
3individual/mL is inoculated on 96 orifice plates, after cell covers with, discards culture medium, adds serum-free medium containing variable concentrations 0,0.1,1,10 μ M myricetrins to orifice plate, cultivates 24h, adds H
2o
2(300 μ M), then cultivate 24h, utilize mtt assay to carry out cytoactive detection.
Result as shown in Figure 1-2, the model of action that abscissa is each group, vertical coordinate is cell viability value, the percent comparing with the OD value of blank group with the absorbance OD value of each group is explained.As seen from the figure, simple H
2o
2after effect, cytoactive reduces, and after the effect of variable concentrations myricetrin, cytoactive increases, with simple H
2o
2effect group is compared, and has significant difference.Represent for No. # in figure: with matched group, compare,
#p<0.05,
##p<0.01; Represent for No. * in figure: with simple H
2o
2effect group is compared, * P < 0.05, * * P < 0.01.This can protect H after showing to process with myricetrin
2o
2the apoptosis of the hBMSC of induction.
In sum, through myricetrin, to hBMSC cytosis, variable concentrations myricetrin carries out pretreatment to cell, then applies H
2o
2intervene, by MTT, detect cytoactive, result shows simple H
2o
2effect can cause cytoactive to reduce, and cause apoptosis, and 0.1,1,10 μ M myricetrin pretreatment has protective effect to this damage.Therefore, myricetrin is to H
2o
2the apoptosis that the oxidative stress of induction causes has protective effect.
2, myricetrin antioxidation detects
After hBMSC cell is paved with, at myricetrin and/or H
2o
2under effect, processing method the same (in 1.2), carries out oxidative stress coherent detection.
According to ROS detection kit, utilize fluorescent probe DCFH-DA to detect intracellular active oxygen.Cell climbing sheet, 0.1,1,10 μ M myricetrin pretreatment 24h, 300 μ M H
2o
2effect 24h, then carries out original position and loads probe, adds 10 μ M DCFH-DA, hatches 20min, with PBS, washes 3 times, removes unconjugated probe, utilizes fluorescence microplate reader to detect.
Result as shown in Figure 2, the model of action that abscissa is each group, vertical coordinate is that ROS generates, the percent comparing with the OD value of blank group with the absorbance OD value of each group is explained.As seen from the figure, simple H
2o
2after processing, intracellular ROS level raises clearly, and after 0.1,1,10 μ M myricetrin pretreatment, intracellular ROS level reduces.Therefore, myricetrin can improve hBMSC oxidative stress ROS level.
3, the protective effect that myricetrin causes hBMSC Osteoblast Differentiation to suppress to oxidative stress
The protective effect that myricetrin causes hBMSC Osteoblast Differentiation to suppress to oxidative stress: experiment grouping the same (in 1.2); cell is laid on 6 orifice plates; after being paved with, add dexamethasone 0.1uM, 10mM sodium glycerophosphate and 50ug/mL ascorbic acid carry out osteogenic induction cultivation.After 14 days, give 0.1,1,10 μ M myricetrin pretreatment 24h, then add 300 μ M H
2o
2process 24h.
3.1 according to alkali phosphatase quantification kit (Shanghai outstanding beautiful), to carry out ALP quantitative, and collecting cell, after cracking, extracts albumen.Measure protein concentration, then according to the explanation of test kit, carry out ALP detection by quantitative.
Result as shown in Fig. 3-1, the model of action that abscissa is each group, vertical coordinate is ALP vigor, the percent comparing with the OD value of blank group with the absorbance OD value of each group is explained.Simple H
2o
2after effect, cell ALP activity expression is compared remarkable decline with blank group, and after myricetrin effect, ALP activity expression raises, with simple H
2o
2effect group is compared has significant difference.ALP is the crucial expressing protein that skeletonization and precursor thereof break up mid-term, for detecting the specific index of skeletonization and precursor differentiation thereof, oxidative stress causes ALP activity decreased, skeletonization and precursor thereof are divided into inhibitory action, but after myricetrin effect, ALP expresses increase, has improved the inhibitory action of oxidative stress to hBMSC Osteoblast Differentiation.
3.2 calcification tuberosity dyeing: with PBS, rinse cultured cell, after paraformaldehyde is fixing, 1% Alizarin red staining 30 minutes, water rinses 5 times, observes calcium tuberosity deposition under inverted microscope.
Grouping situation: 1. blank group; 2. simple H
2o
2processed group; 3. 0.1 μ M Myricitrin+H
2o
2; 4. 1 μ M Myricitrin+H
2o
2; 5. 10 μ M Myricitrin+H
2o
2.
Result as shown in Fig. 3-2, simple H
2o
2the rear calcification tuberosity of effect forms less, but after myricetrin pretreatment, knuckle area has increase.Calcium nodiform becomes the mineralization stage of skeletonization and precursor differentiation thereof, and oxidative stress can suppress skeletonization and precursor differentiation thereof, and myricetrin can improve hBMSC Osteoblast Differentiation by improving oxidative stress.
The RT-PCR of 3.3 osteogenesis genes detects: experiment grouping the same (in 1.2), cell is laid on 6 orifice plates, and after being paved with, add 0.1uM dexamethasone, 10mM sodium glycerophosphate and 50ug/mL ascorbic acid carry out osteogenic induction cultivation.After 14 days, give 0.1,1,10 μ M myricetrin pretreatment 24h, then add 300 μ M H
2o
2process 24h.Use Trizol cell lysis, extract intracellular mRNA, according to the program of real-time quantitative RT-PCR, genes of interest Alp, Colla1 and Ocn are carried out to detection by quantitative.
Result as shown in Fig. 3-3A, Fig. 3-3B, Fig. 3-3C, the model of action that abscissa is each group, relative expression's level that vertical coordinate is mRNA, explains with respect to the percentage rate of blank group with each group.As seen from the figure, H
2o
2after effect, cell Osteoblast Differentiation Gene A lp, Colla1 and Ocn expression decline, and after myricetrin effect, can significantly promote osteogenesis gene to express.Alp, Colla1 and Ocn gene are respectively the key gene in skeletonization and precursor differentiation mid-term and later stage, are determining the level of differentiation of cell.H
2o
2suppress the expression of skeletonization and precursor Osteoblast Differentiation gene thereof, and after myricetrin effect, Osteoblast Differentiation gene expression there is rise, illustrates that myricetrin can improve H
2o
2the hBMSC Osteoblast Differentiation causing suppresses.
4, the inhibitory action that the hBMSC that myricetrin causes oxidative stress becomes fat to strengthen
4.1 the generation of detected with oil red O lipid: become fat induction after 14 days, cell is through myricetrin and/or H
2o
2process 2 days, with PBS, rinse cell, 3.7% formaldehyde is fixed 20 minutes, then dyes 1 hour with oil red O liquid.
Grouping situation: 1. blank group; 2. simple H
2o
2processed group; 3. 0.1 μ M Myricitrin+H
2o
2; 4. 1 μ M Myricitrin+H
2o
2; 5. 10 μ M Myricitrin+H
2o
2.
Result as shown in Fig. 4-1, simple H
2o
2it is more that after effect, fat drips formation, but after myricetrin pretreatment, fat drips to generate obviously and reduces.Lipid is generated as mesenchymal stem cells MSCs to the sign that becomes fat differentiation, and oxidative stress can promote into fat differentiation, and myricetrin can suppress hBMSC and becomes fat to break up by improving oxidative stress.
The RT-PCR of 4.2 one-tenth fat genes detects: experiment grouping the same (in 1.2), cell is laid on 6 orifice plates, and after being paved with, then become fat induction 14 days, give afterwards 0.1,1,10 μ M myricetrin pretreatment 24h, then add 300 μ M H
2o
2process 24h.Use Trizol cell lysis, extract intracellular mRNA, according to the program of real-time quantitative RT-PCR, genes of interest PPAR γ 2 is carried out to detection by quantitative.
Result as shown in Fig. 4-2, the model of action that abscissa is each group, relative expression's level that vertical coordinate is mRNA, explains with respect to the percentage rate of blank group with each group.As seen from the figure, H
2o
2after effect, cell becomes fat differentiation gene PPAR γ 2 expressions to raise, and after myricetrin effect, can significantly be suppressed to the expression of fat gene.PPAR γ 2 is into the key gene of fat and precursor differentiation thereof, is determining to a certain extent the level of differentiation of cell.H
2o
2promote into the expression of fat differentiation gene, and after myricetrin effect, become fat differentiation gene down-regulated expression, illustrate that myricetrin can suppress H
2o
2the hBMSC causing becomes fat differentiation.5, the expression impact of myricetrin on bone resorbing factor
The inhibitory action that myricetrin stimulates bone resorbing factor to increase to oxidative stress: divide into groups the same (in 1.2), cell is laid on 6 orifice plates, after being paved with, carry out osteogenic induction cultivation, after 14 days, give myricetrin and process, then add H
2o
2, cell lysis, extracts albumen, measures protein concentration, detects the expression of IL-6 and RANKL according to enzyme-linked immunosorbent assay (ELISA method).
Result as shown in Fig. 5 A, Fig. 5 B, the model of action that abscissa is each group, the relative expression quantity that vertical coordinate is bone resorbing factor, explains with respect to the percentage rate of blank group with each group.H
2o
2after effect, the IL-6 of cellular expression and RANKL level increase, and myricetrin pretreatment can suppress the expression of bone resorbing factor.IL-6 and RANKL are the cytokine of skeletonization and precursor secretion thereof, can activate osteoclast, and then cause that bone resorption strengthens, and cause bone amount to reduce.Therefore, myricetrin can suppress the activation of osteoclast by suppressing the expression of IL-6 and RANKL, and then reduces the loss of bone amount.
Comprehensive above showing: myricetrin, to human marrow mesenchymal stem cell free of toxic effects, does not affect cell proliferation; To H
2o
2the apoptosis of the human marrow mesenchymal stem cell causing has protective effect; And improve H in its atomization
2o
2the oxidative stress status of induction; To H
2o
2the human marrow mesenchymal stem cell Osteoblast Differentiation causing suppresses to have protective effect; To H
2o
2the human marrow mesenchymal stem cell causing becomes fat differentiation to strengthen inhibited; Can suppress the expression of bone resorbing factor, thereby activate osteoporosis is shielded with the indirect inhibition of differentiation inhibition osteoclast by improving human marrow mesenchymal stem cell apoptosis.
6. the foundation of animal bone rapping type
40 8 weeks large BALB/c female mices, body weight is 20-22g.The initial body weight no difference of science of statistics of 4 groups of mices in this experiment.Before spay, first they are placed in 1 week (the 20 ℃ of good isoperibols of ventilating, alternately, water grain is enough, freely takes for every 12 hours illuminations) under laboratory condition.Adapt to after 1 week, with pentobarbital sodium (50mg/kg body weight), anaesthetize, and the cut ovary of mice (castration, n=30) or sham-operation (n=10).Oophorectomize is by dorsal part approach for resection bilateral ovaries.Sham-operation means to perform the operation finds bilateral ovaries, but does not excise, and directly sews up and closes otch.Mice is divided into 4 groups at random: not processed group (Sham-operated control group, Sham); Not processed group (simple oophorectomize group, OVX); Low dosage myricetrin administration group (after oophorectomize every day give by lumbar injection the myricetrin solution of 5mg/kg body weight, OVX+Myricitrin (5)); High dose myricetrin administration group (after oophorectomize every day give by lumbar injection the myricetrin solution of 25mg/kg body weight, OVX+Myricitrin (25)).Myricetrin is dissolved in deionized water, by lumbar injection to processed group injected in mice same volume deionized water not.Within after operation 1 week, start administration, successive administration 12 time-of-weeks.After administration completes, under anesthesia, by heart, take a blood sample and obtain blood preparation, and carry out centrifugal.Extract left side femur and the fourth lumbar vertebra of every mice, remove the muscular tissue of adhesion, properly fixing.
6.1 use lipid peroxide MDA detection kit to detect respectively organizes blood sample.In lipid peroxidation process, thiobarbituricacidα-is combined with MDA and is generated colour developing complex, and its maximum absorption band, at 532nm, utilizes microplate reader reading herein.Equally, use GSH detection kit to detect and respectively organize blood sample.The detection of GSH is according to GSH, to react with dithio dinitrobenzoic acid (DTNB) to form a product, and this product carries out reading detection by microplate reader at 412nm place.
Result as shown in Fig. 6-1A and Fig. 6-1B, the model of action that abscissa is each group, vertical coordinate is MDA vigor and GSH vigor, the percent comparing with the OD value of blank group with the OD value of each group is explained.As seen from the figure, simple H
2o
2after processing, the MDA level in serum obviously raises, and GSH level obviously reduces; And MDA level in the myricetrin administration group serum of high and low dose reduces, GSH level raises.Therefore, myricetrin can improve oxidative stress status in serum.
6.2 micro-CT detect bone micro-structure: the bone micro-structure of fourth lumbar vertebra and distal femur detects by exploring the micro-CT of the pre-clinical samples of track SP.Resolution is 8mm, and tube voltage is 50kV, and tube current is 0.1mA.By a micro-CT process software of desktop, rebuild and 3D quantitative analysis.The scanning circumstance of all specimen is identical with analytical method.Femur scanning area is defined as distal stem dirt end, and extends 2.0mm to the elementary spongiosa proximal end region of near-end.After having got rid of skull and tail endplate regions, the cancellous bone region of vertebral body is comprised in each micro-CT constituency.In these regions to be scanned, the boundary of spongy bone and cortical bone is inner cortex surface of bone.The 3D parameter of selected region of interest, for data analysis, comprising: bone mineral density, Connection Density, structural model index, bone trabecula quantity, bone trabecula thickness, bone trabecula separating degree and relative bone volume mark.The operator who carries out scanning analysis is blind to the processing procedure list of specimen.
Result is as shown in Fig. 6-2, and with respect to sham operated rats, oophorectomize has caused the infringement of mice Grafting Cancellous Bone Bolt micro structure, shows as the decline of bone mineral density, Connection Density, bone trabecula quantity, bone trabecula thickness and bone volume mark.Meanwhile, after oophorectomize, structural model exponential sum bone trabecula separating degree obviously improves.Result has significant difference.Yet high and low dose myricetrin administration group has obviously reversed the variation tendency of the bone micro-structure parameter that oophorectomize causes, plays the effect that keeps fourth lumbar vertebra and distal femur trabecular bone bone amount, result has significant difference.Therefore, myricetrin can be to postmenopausal osteoporosis performance prevention and therapeutical effect.
6.3 are dyeed and are carried out histology by VG: the left side femur of mice is fixed 48 hours with 4% paraformaldehyde after having drawn materials.All specimen 80% dehydration of alcohol, and carry out embedding with polymethyl methacrylate (PMMA).With rotary microtome, cut the Coronal thin slice that 240mm sheet is thick, then all sections are polished into 20mm sheet thick, for carrying out VG dyeing.
Result is as shown in Fig. 6-3, and with respect to sham operated rats, oophorectomize group bone trabecula quantity obviously declines, and the distance between girder obviously broadens.Give after high and low dose myricetrin drug treating, above-mentioned bone trabecula infringement successful improves, and shows as the increase of bone trabecula quantity and reducing of bone trabecula spacing.
Therefore, myricetrin can be applicable to osteoporotic control, be especially applied in preparation control medicine for treating osteoporosis in.
Claims (9)
1. myricetrin is in the application for the preparation of in the osteoporotic medicine of control.
2. contain the plant extract of myricetrin in the application for the preparation of in the osteoporotic medicine of control.
3. myricetrin is in the application for the preparation of improving in the medicine of human marrow mesenchymal stem cell oxidative stress status.
4. the application of myricetrin in the medicine for the preparation of anti-human marrow mesenchyma stem cell apoptosis.
5. the application of myricetrin in the medicine suppressing for the preparation of anti-human marrow mesenchyma stem cell Osteoblast Differentiation.
6. application as claimed in claim 5, is characterized in that, the application of myricetrin in the medicine for the preparation of ALP activity in improving human marrow mesenchymal stem cell.
7. application as claimed in claim 5, is characterized in that, myricetrin is in the application for the preparation of facilitating in improving human marrow mesenchymal stem cell in the medicine of bone differentiation gene Alp, Colla1 and Ocn expression.
8. application as claimed in claim 5, is characterized in that, myricetrin is in the application for the preparation of suppressing in improving human marrow mesenchymal stem cell in the medicine of RANKL and IL-6 level.
9. the application as described in any one in claim 1～8, is characterized in that, the dosage of myricetrin is at least 5mg/kg.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111084780A (en) * | 2020-01-09 | 2020-05-01 | 昆明医科大学 | Application of geraniin in preparing medicine for treating osteoporosis and fracture |
| CN112656814A (en) * | 2019-11-14 | 2021-04-16 | 施松涛 | Application of chaetocin, UNC0642 or mesenchymal stem cells in treating diseases caused by mesenchymal stem cell damage and delaying senescence |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1837169A (en) * | 2006-03-14 | 2006-09-27 | 房学迅 | Compound capable of inhibiting zinc ion metalloproteinases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1837169A (en) * | 2006-03-14 | 2006-09-27 | 房学迅 | Compound capable of inhibiting zinc ion metalloproteinases |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112656814A (en) * | 2019-11-14 | 2021-04-16 | 施松涛 | Application of chaetocin, UNC0642 or mesenchymal stem cells in treating diseases caused by mesenchymal stem cell damage and delaying senescence |
| CN111084780A (en) * | 2020-01-09 | 2020-05-01 | 昆明医科大学 | Application of geraniin in preparing medicine for treating osteoporosis and fracture |
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