CN105853453A - Application of baicalin in preparation of medicine for protecting heart development of fetus with pregnancy associated with diabetes - Google Patents
Application of baicalin in preparation of medicine for protecting heart development of fetus with pregnancy associated with diabetes Download PDFInfo
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Abstract
The invention belongs to the field of traditional Chinese medicine, and particularly discloses application of baicalin in preparation of medicine for protecting heart development of a fetus with pregnancy associated with diabetes. A chick embryo test is conducted by adopting the traditional Chinese medicine monomer baicalin, and a result proves that a certain concentration of baicalin cannot cause chicken embryo development malformation and can effectively relieve adverse embryo heart development induced by a high glucose environment. According to the novel application of baicalin in the medicine field, the application range of baicalin is widened, the application value of baicalin is increased, and a contribution is brought for further development of new medicine, for example, the activity of baicalin is expected to be further improved or the side effects of baicalin are expected to be reduced by taking baicalin as a lead compound through structural modification or transformation.
Description
Technical field
The invention belongs to the field of Chinese medicines, be specifically related to baicalin and send out at preparation pregnancy associated with diabetes heart of fetus
Educate the application in protection medicine.
Background technology
In recent years, along with the raising of people's living standard, dietary habit and living-pattern preservation, gestation is closed
And the sickness rate of diabetes in the whole world all in the trend risen year by year, become the public health problem of various countries.Portugal
Grape sugar can pass through placental barrier, and the fetal parenchymal of pregnancy associated with diabetes is in the ring of a high glucose
Border, report the congenital malformation in recent ten of fetus of Diabetic Pregnancy higher than non-diabetic gestation 2-5 times, mainly
Show as congenital heart disease and nervous system abnormality.
Pregnancy associated with diabetes patient is the crowd that a class is special, and primary treatment measure is that insulin treatment is dropped
Low internal blood sugar concentration.Owing to the liver development imperfection of fetus, medicine and catabolite excretion are prolonged, and row
The part metabolite removed, can heavily be absorbed by fetus because of " circulation of amniotic fluid intestinal ", accumulate the most in vivo,
Affect the growth of fetal tissue's organ.During gestation, even if to parent without the medicine of serious untoward reaction
It is likely to fetus is produced toxic action.The oral drugs of Current therapeutic diabetes include metformin, methose
Peaceful and chlorpropamide etc. all specify that anemia of pregnant woman should not use.
In motherland's medical science, take Chinese medicine protection normal fetal growth promoter, prevented miscarriage, premature labor, deformity
There is long history, have accumulated abundant clinical experience, in terms of clinical treatment, highlight the advantage of self.
Radix Scutellariae is traditional antiabortive famous medicine, and medicine source is extensive, cheap, without obvious toxic-side effects.The antibacterial of Radix Scutellariae resists
Virus, antiinflammatory, antiallergic, blood fat reducing, protect the liver, function of gallbladder promoting is the pharmacological basis of its heat clearing and damp drying；Calm,
Removing toxic substances, diuresis, blood pressure lowering, antioxidation, antitumor etc. are the modern times foundations of its eliminating fire and detoxication.Radix Scutellariae is suitable for
Trimester of pregnancy takes, because having the pharmacological actions such as antiinflammatory, antioxidation, calmness, blood pressure lowering, vasodilator smooth muscle,
Placental blood can be improved supply.Not only there is preventing and treating to recurrent abortion, preeclampsia, intrauterine growth retardation etc. make
With, when can reduce product simultaneously, puerperal infection, favourable puerperal uterus hemostasis and restoration of old ways process.Baicalin
(Baicalin) being to extract a kind of flavone compound separated from scutellariae,radix, molecular formula is
C21H18O11, molecular weight is 446.35, has the most fat-soluble, can pass through placental barrier.Have antibacterial,
The physiological potencies such as diuresis, antiinflammatory, resistance state, spasmolytic and stronger antitumor response, occupy at clinical medicine
Critical role, current existing multiple manufacturer production baicalin sheets, it is mainly used in acute hepatitis, chronic hepatitis, delay
Property hepatitis auxiliary treatment, to Pregnant and lactant women medication indefinite.
The patent of baicalin focuses mostly in its extractive technique, and such as a kind of Radix Scutellariae hairy root baicalin that improves produces
The method (201410143966.0) of amount, a kind of method (201410502598.4) rapidly and efficiently extracting baicalin,
A kind of biological enzyme produces the extracting method (201510156727.3) etc. of baicalin.Application side at baicalin
Face, focuses mostly on its antiinflammatory, the patent of antibiosis, such as baicalin answering in preparing oral care product
By (201310489646.6), baicalin purposes (200910004166.X) in preparation protection target organ medicine
Deng.
Summary of the invention
It is an object of the invention to provide the new application of a kind of baicalin, not only expand the range of application of baicalin,
Improve its using value, additionally aid and develop new medicine further, such as with baicalin for guide's chemical combination
Thing, by structural modification or transformation, or is expected to improve its activity further or reduce side effect.
For realizing the object of the invention, the technical scheme is that
There is provided Chinese medicine monomer baicalin preparation pregnancy associated with diabetes heart of fetus grow protection medicine in new
Purposes.
Described medicine is pharmaceutically acceptable any dosage form, can be pharmaceutically acceptable containing one or more
Carrier or excipient.
Although Radix Scutellariae is traditional antiabortive famous medicine, but its extract baicalin is for gestational diabetes fetus
Protective effect is still not clear.Current therapeutic pregnancy associated with diabetes mainly uses insulin to treat, but price
Relatively high, can there is anaphylaxis in some patients, can cause neonatal hypoglycemia.Oral antidiabetic drug includes
Metformin, tolbutamide and chlorpropamide etc. all specify that anemia of pregnant woman should not use.The most currently there is no peace
The heart development of full oral drugs protection pregnancy associated with diabetes fetus.Present invention discover that finite concentration Radix Scutellariae
Glycosides is not result in fetal development deformity, and can effectively alleviate the embryonic heart development of high sugar environmental induction not
Good.Chinese medicine monomer baicalin molecular formula of the present invention is C21H18O11, molecular weight is 446.35, structure
Formula is as shown in Figure 1.The invention provides baicalin or it can as the trim that lead compound is synthesized
Using the raw material as pharmaceutical preparation, make together with one or more pharmaceutically acceptable carriers or excipient
Pharmaceutically acceptable any dosage form also has the medicine protecting pregnancy associated with diabetes heart of fetus growth effect
The new application of thing.
Present invention application Embryo Gallus domesticus sets up the model (Cell Cycle:14 (5): 772-783. of pregnancy associated with diabetes fetus
2015), find that high sugar environment can be by the expression of the key genes such as mediated cell autophagy and suppression GATA4
Causing embryo heart deformity, this is to the invention provides a good research protection pregnancy associated with diabetes tire
Youngster grows the in vivo model of medicine.
The present invention uses Chinese medicine monomer baicalin to carry out Embryo Gallus domesticus test, and result proves, finite concentration baicalin
It is not result in chick embryo development deformity, and the embryonic heart development that can effectively alleviate high sugar environmental induction is bad,
Specifically have the advantage that
(1) finite concentration baicalin does not interferes with chick embryo development.
(2) baicalin can significantly improve embryonic death and the developmental disorder that high sugar environment causes.
(3) baicalin can significantly improve the heart pipe developmental disorder that high sugar environment causes, and regulates corresponding heart pipe and grows base
Cause.
(4) baicalin can significantly improve the apoptosis of high sugar environmental induction.
Accompanying drawing explanation
Fig. 1 is the chemical constitution of baicalin.
Fig. 2 is the impact on early embryo development of the variable concentrations baicalin.
Fig. 3 is that variable concentrations baicalin is on the impact of early embryo development under high sugar environment.
Fig. 4 is the impact that heart pipe under high sugar environment is grown by baicalin.
Fig. 5 is that baicalin is on chick-embryo cell autophagy and the impact of apoptosis under high sugar environment.
Detailed description of the invention
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but the embodiment party of the present invention
Formula is not limited to this.Chinese medicine monomer baicalin described in the embodiment of the present invention is purchased from Santa Cruz (sc-204638).
Embodiment 1: finite concentration baicalin does not interferes with chick embryo development
The method using Early chick (EC) Culture cultivates early chick embryo, and Embryo Gallus domesticus is divided into normal group
(0.1% dimethyl sulfoxide DMSO) and baicalin group (DMSO dissolves baicalin).Baicalin DMSO
After dissolving, experimental group working solution DMSO concentration used is less than 0.1%.The baicalin of variable concentrations is joined
After EC Culture cultivate Embryo Gallus domesticus to the HH11 phase (0 μM: n=30,3.125 μMs: n=30,6.25 μMs: n=30,
12.5 μMs: n=27 and 25 μMs: n=30).Finding 3.125 μMs, the baicalin of 6.25 μMs is to 26h, 39h
Substantially have not significant impact with the fetal development of 48h, with normal group embryo (0 μM) plesiomorphism (Fig. 2
In A-C3), body segment number (judging the significant structure of Embryo Gallus domesticus early development stage) do not have statistics have a mind to
Justice (p > 0.05).12.5 μMs, the normal growth of Embryo Gallus domesticus part under the conditions of 25 μMs, there is individual developmental stagnant
Afterwards (C2 in Fig. 2, C3), 48h body segment logarithm reduces (p < G in 0.01, Fig. 2) compared with normal group；
And some Embryo Gallus domesticus occur in that severe deformities (H-I in Fig. 2), 12.5 μMs of baicalin severe deformities rates are
33.33%, the severe deformities rate of 25 μMs of baicalins is 50% (J in Fig. 2).
It is experimentally confirmed that in Embryo Gallus domesticus model, the baicalin of less than 6.25 μMs concentration does not affect early embryo development.
Embodiment 2: baicalin can significantly improve embryonic death and the developmental disorder that high sugar environment causes.
The gestational diabetes Embryo Gallus domesticus model (Cell Cycle:14 (5): 772-783.2015) having built up based on us,
We set up Embryo Gallus domesticus normal group (0.1%DMSO), high sugar group (50mM glucose), baicalin low concentration group
(6.25 μMs), concentration group (6.25 μMs) 4 groups (n=10) in baicalin, trains in 4 groups of EC Culture
Poultry embryo, to the HH11 phase, carries out the statistics of developmental stage and abnormal rate.We are permissible for A-A1 from Fig. 3
Observing that normal group fetal development is good, form is normal；The partial embryonic (B-B3 in Fig. 3) of high sugar process group
Substantially observing serious deformity (B3 in 50%, Fig. 3) at 48h, fetal development is delayed (in Fig. 3
E), body segment logarithm reduces (p < 0.001) compared with normal group；Under high sugar environment, 3.125 μMs of baicalins process
Embryo (C-C3 in Fig. 3) also have more serious deformity, incidence rate is 50%, and fetal development is delayed also
Be not restored (E-F in Fig. 3), and body segment logarithm reduces (p < 0.001) compared with normal group；High sugar ring
Under border, embryo (D-D3 in Fig. 3) major part that 6.25 μMs of baicalins process is it can be seen that fetal development
Period and the recovery of form, severe deformities rate is 20% (E-F in Fig. 3), body segment logarithm and normal group phase
Ratio there was no significant difference (p > 0.05).
It is experimentally confirmed that in Embryo Gallus domesticus model, the baicalin of 6.25 μMs of concentration significantly improves what high sugar environment caused
Dysontogenesis.
Embodiment 3: baicalin can significantly improve the heart pipe developmental disorder that high sugar environment causes, and regulates corresponding heart pipe
Development gene.
The immunofluorescence state tubular to the Embryo Gallus domesticus heart using MF-20 is observed.It may be seen that normal group and
The embryo of 6.25 μMs of baicalin process is at HH11+Heart pipe presents C-shaped ring (A-B in Fig. 4), and high
The embryo of sugar process group severe deformities occurs in that heart pipe abnormal fusion (C in Fig. 4), application baicalin process
After the embryo that is restored, its heart pipe presents normal C-shaped ring.The method that we use RT-PCR subsequently
Have detected heart pipe differentiation gene VMHC, mesoderm icam gene N-Cadherin and heart pipe differentiation controlling gene
The mRNA level in-site of BMP2, it has been found that 6.25 μMs of baicalins are to VMHC, N-Cadherin and BMP2
MRNA level in-site do not significantly affect (p > 0.05), and high sugar environment can suppress the expression of above gene
(p<0.01).Under high sugar environment, application baicalin intervention can significantly recover VMHC, N-Cadherin
Mrna expression level (p < E-E1 in 0.01, Fig. 4) with BMP2.Use the side of Western blot
Method, we have detected the expression of GATA4, it has been found that 6.25 μMs of baicalins albumen to GATA4
Level does not significantly affect (p>0.05), and high sugar environment can suppress GATA4 to express (p<0.05).?
Under high sugar environment, application baicalin intervention can significantly recover the expression of GATA4, and (p is < in 0.01, Fig. 4
F-F1).
It is experimentally confirmed that in Embryo Gallus domesticus model, the baicalin of 6.25 μMs of concentration significantly improves what high sugar environment caused
Embryo makes up one's mind, and pipe is lopsided and heart pipe is grown important gene and expressed.
Embodiment 4: baicalin can significantly improve the chick-embryo cell apoptosis of high sugar environmental induction
Cell autophagy level and apoptotic increase can be caused based on high sugar environment, application Western blot's
Method, the expression of detection cell autophagy albumen LC3B and Beclin1, it has been found that 6.25 μMs of Radix Scutellariaes
Although glycosides can promote LC3B II/LC3B I and Beclin1, but result do not have significant difference (Fig. 5,
P>0.05), and high sugar environment can remarkably promote can promote LC3B II/LC3B I and Beclin1 (Fig. 5, P<0.01,
P<0.05).Under high sugar environment, application baicalin intervention suppression LC3B II/LC3B I and Beclin1, though
So compared with height sugar group, result no difference of science of statistics, but compared with normal group, difference is not the most notable (P > 0.05).
Simultaneously, it has been found that high sugar environment can remarkably promote the expression (Fig. 5, P < 0.001) of C-caspase3, Radix Scutellariae
Glycosides does not affect the expression (Fig. 5, P > 0.05) of C-caspase3, after applying baicalin to intervene under high sugar environment,
The expression of C-caspase3 substantially reduces (Fig. 5, P < 0.01).
It is experimentally confirmed that in Embryo Gallus domesticus model, the baicalin of 6.25 μMs of concentration significantly improves high sugar environmental induction
Apoptosis.
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention are not by above-mentioned reality
Execute the restriction of example, the change made under other any spirit without departing from the present invention and principle, modification,
Substitute, combine, simplify, all should be the substitute mode of equivalence, within being included in protection scope of the present invention.
Claims (2)
1. baicalin application in preparation pregnancy associated with diabetes heart of fetus grows protection medicine.
Application the most according to claim 1, it is characterised in that described medicine is pharmaceutically acceptable
Any dosage form, described medicine can contain one or more pharmaceutically acceptable carrier or excipient.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381473A (en) * | 2018-11-26 | 2019-02-26 | 暨南大学 | Scutelloside is in the application for preparing gestational diabetes Fetal neurotubules malformation drug |
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| CN101422507A (en) * | 2008-12-04 | 2009-05-06 | 深圳海王药业有限公司 | Combination of baicalin and atractylodes macrocephala lactone and preparation method thereof |
| CN104152404A (en) * | 2014-09-04 | 2014-11-19 | 青岛农业大学 | Embryo heat resistance improving culture solution and using method thereof |
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2016
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| CN101422507A (en) * | 2008-12-04 | 2009-05-06 | 深圳海王药业有限公司 | Combination of baicalin and atractylodes macrocephala lactone and preparation method thereof |
| CN104152404A (en) * | 2014-09-04 | 2014-11-19 | 青岛农业大学 | Embryo heat resistance improving culture solution and using method thereof |
Non-Patent Citations (2)
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| 颜小华等: "黄芩苷体外诱导人脐血间充质干细胞向神经元样细胞的分化", 《中国组织工程研究与临床康复》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381473A (en) * | 2018-11-26 | 2019-02-26 | 暨南大学 | Scutelloside is in the application for preparing gestational diabetes Fetal neurotubules malformation drug |
| CN109381473B (en) * | 2018-11-26 | 2020-05-08 | 暨南大学 | Application of baicalin in preparation of medicine for preventing gestational diabetes mellitus fetal neural tube malformation |
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