CN116920013A - Traditional Chinese medicine composition for treating or preventing preeclampsia - Google Patents
Traditional Chinese medicine composition for treating or preventing preeclampsia Download PDFInfo
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- CN116920013A CN116920013A CN202310969568.3A CN202310969568A CN116920013A CN 116920013 A CN116920013 A CN 116920013A CN 202310969568 A CN202310969568 A CN 202310969568A CN 116920013 A CN116920013 A CN 116920013A
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- preeclampsia
- chinese medicine
- traditional chinese
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- A61K31/33—Heterocyclic compounds
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Abstract
The application provides a traditional Chinese medicine composition for treating or preventing preeclampsia. The inventor of the application unexpectedly discovers that the composition of the baical skullcap root extract and the largehead atractylodes rhizome extract can obviously reduce the contraction pressure of mice, reduce the urine protein content of the mice in a preeclampsia model mouse intervention experiment, obviously observe the treatment improving effect in placenta pathological sections and kidney pathological sections, and can effectively treat preeclampsia and protect the physiological structures of kidneys and embryo tissues; therefore, the inventor further verifies and discovers that baicalin, baicalein and atractylenolide I have a promoting effect on migration of HTR-8/Svneo cells under a specific concentration, and shows that the traditional Chinese medicine composition has an effect on treating or preventing preeclampsia, can condition yin-yang balance of a eclampsia patient on the whole, shows the effect on treating or preventing preeclampsia through multi-target effect, and is consistent with a complex pathogenesis of preeclampsia.
Description
Technical Field
The application relates to a traditional Chinese medicine composition for treating or preventing preeclampsia, and belongs to the technical field of traditional Chinese medicines.
Background
PE is a disease special for gestation, the occurrence after 20 weeks of gestation is 3-8% of the global incidence, the number of deaths of pregnant women caused by the annual factor epilepsy is about 7600-8200, the second cause of the deaths of the pregnant women is the second cause, and the preeclampsia maternal fetal dead uterus rate before 32 weeks of gestation is as high as 33.3%. Meanwhile, the incidence risk of the leukoencephalopathy syndrome which occurs when eclampsia is caused by the long-term cardiovascular disease of eclampsia patients, especially severe eclampsia patients, is obviously increased, and the morbidity and mortality of the surrounding infants caused by the eclampsia of the mother are greatly increased. The higher early preventive medication can effectively reduce the occurrence risk of the lesion damage of a preeclampsia patient, can reduce the occurrence probability of eclampsia, lighten the family burden and the social medical and economic burden brought by complications of pregnant women with potential eclampsia risk, effectively saves medical resources, and has non-negligible economic value and social benefit.
According to the guidelines for diagnosis and treatment of hypertensive disorders during pregnancy published in China 2015, the high risk factors of preeclampsia include age not less than 40 years, primordial age, body Mass Index (BMI) not less than 28, multiple pregnancy, preeclampsia family history (mother or sister), preeclampsia history and existing medical history or hidden existing (potential) diseases (including primary hypertension, renal diseases, diabetes and autoimmune diseases such as systemic lupus erythematosus and antiphospholipid syndrome), and the like. In multiple gestation, in vitro fertilization-embryo transfer (IVF-ET) increases the risk of developing preeclampsia. In addition, the existing pregnant women with gestational hypertension disease history can cause the disease susceptibility genes, preeclampsia is more likely to occur when the pregnant women are pregnant again, the preeclampsia occurrence risk of the pregnant women with the hypertension family history is obviously increased, and the preeclampsia occurrence risk is increased year by year along with the application of auxiliary reproduction technology and the release of the two-child policy, so that the incidence rate of preeclampsia is also increased year by year, thereby the development of safe and effective preeclampsia preventive measures is important.
The currently known measures for preventing preeclampsia mainly comprise adjusting the dietary structure, proper exercise, taking aspirin in small doses, supplementing folic acid and the like. Among these measures, in addition to the small dose of aspirin (50-100 mg) being listed in the diagnosis and treatment guidelines for hypertensive disorders of pregnancy (2015), further studies and verification remain. In addition, measures such as bed rest, sodium limitation, intake of fish oil, folic acid, garlic, vitamins C, E and D have not formed a universal application regimen and have not been converted to clinical benefit.
Currently known protocols for the treatment of preeclampsia, such as administration of phosphodiesterase type 5 inhibitors (sildenafil/122), can result in reduced blood pressure, increased fetal weight, reduced uterine arterial resistance, and improved angiogenic balance. For example, the American society of gynaecologists, the American society of preventive services and the International society of research on pregnancy and hypertension suggest that high-risk women after 12 weeks of gestation take aspirin daily to reduce their risk of preeclampsia (aspirin is believed to reduce the risk of preeclampsia by inhibiting cyclooxygenase-1 and cyclooxygenase-2, both enzymes contributing to prostaglandin biosynthesis and subsequent endothelial dysfunction). Calcium supplement can reduce uterine smooth muscle contractility, and can improve uterine placenta blood flow, and prevent premature delivery. Pravastatin has been proposed as an adjuvant therapy to reduce the risk of preeclampsia. Data from pre-eclampsia mice models indicate that pravastatin can prevent vascular dysfunction.
Currently, more and more researchers are engaged in pre-eclampsia prevention studies, but no general application scheme is formed. For example, oxidative stress is associated with the onset of preeclampsia, and thus antioxidants vitamin C and E have been proposed to prevent preeclampsia. Several randomized and placebo controlled studies have found that oral administration of vitamin C, E does not reduce the risk of preeclampsia. A recently published random control study found that pregnant women supplemented with calcium, magnesium, zinc, vitamin D had a lower PE occurrence than the placebo group, and the differences were statistically significant, whereas pregnant women supplemented with vitamin C, E had a PE occurrence that was not statistically significant as the differences from the control group. For people with low calcium intake (< 600 mg/d), oral calcium supplementation of at least 1g/d is recommended to reduce to some extent the risk of preeclampsia, especially for pregnant women with insufficient basal calcium intake. Vitamin D deficiency is also suspected to be one of the risk factors for preeclampsia. However, whether vitamin D supplementation is effective is still unknown. After comprehensive evaluation, obese pregnant women without other high risk factors such as abortion, premature birth and the like can control weight by adjusting diet and proper exercise. Foreign studies have shown that pregnant women with a history of preeclampsia use low molecular heparin and small doses of aspirin prophylactically 16 weeks prior to gestation, reducing the incidence of preeclampsia and fetal growth restriction compared to aspirin alone. The risk of preeclampsia is reduced by taking folic acid supplements and dietary folic acid intake both before and during pregnancy, but this protective effect is statistically significant at a pre-pregnancy BMI <24.0kg/m 2. In view of the above, currently there is a lack of a universal treatment regimen for preeclampsia patients.
Accordingly, it would be desirable for those skilled in the art to be able to develop a traditional Chinese medicine composition for treating or preventing preeclampsia.
Disclosure of Invention
In order to solve the technical problems, the first aspect of the application provides a traditional Chinese medicine composition, wherein the traditional Chinese medicine composition comprises a baical skullcap root extract and a largehead atractylodes rhizome extract, and the mass ratio of the baical skullcap root extract to the largehead atractylodes rhizome extract is 0.6-0.8: 1.
preferably, the traditional Chinese medicine composition is in the form of decoction, tablets, capsules or granules.
The second aspect of the application provides application of the traditional Chinese medicine composition in preparing medicines for preventing and/or treating preeclampsia.
The third aspect of the application provides a traditional Chinese medicine composition, wherein the traditional Chinese medicine composition comprises baicalin, baicalein and atractylenolide I.
Preferably, according to the mole parts, the content of baicalin is 0.001-1 part, the content of baicalein is 0.01-0.5 part, and the content of atractylenolide I is 1-20 parts.
Preferably, the content of baicalin is 0.1 part, and the content of atractylenolide I is 10 parts according to mole parts.
Preferably, the traditional Chinese medicine composition is in the form of decoction, tablets, capsules or granules.
The fourth aspect of the application provides application of the traditional Chinese medicine composition in preparing medicines for preventing and/or treating preeclampsia.
The application provides a traditional Chinese medicine composition for treating or preventing preeclampsia. The inventor of the application unexpectedly discovers that the composition of the baical skullcap root extract and the largehead atractylodes rhizome extract can obviously reduce the contraction pressure of mice, reduce the urine protein content of the mice in a preeclampsia model mouse intervention experiment, obviously observe the treatment improving effect in placenta pathological sections and kidney pathological sections, and can effectively treat preeclampsia and protect the physiological structures of kidneys and embryo tissues; therefore, the inventor further verifies the promotion effect of the medicinal components (baicalein and baicalin) of the radix scutellariae and the medicinal components (atractylenolide I and atractylenolide III) of the rhizoma atractylodis macrocephalae on the invasion and migration of placenta trophoblast cells, and discovers that the baicalin, the baicalein and the atractylenolide I have promotion effect on the migration of HTR-8/Svneo cells under specific concentration, thereby indicating that the traditional Chinese medicine composition has an effect on treating or preventing preeclampsia.
In a word, the traditional Chinese medicine composition disclosed by the application can be used for regulating yin-yang balance of a eclampsia patient on the whole, and the treatment effect of preeclampsia is shown through multi-target effect.
Drawings
FIG. 1 is a graph showing the monitored systolic blood pressure data of a pre-eclampsia model mouse after intervention of the traditional Chinese medicine composition of examples 1-3;
FIG. 2 is a graph showing the results of urine protein detection obtained after intervention of the traditional Chinese medicine composition of examples 1-3 on a preeclampsia model mouse;
FIG. 3 shows the results of HE staining of placental tissue (pathological section of placental tissue) in a mouse model after intervention of the traditional Chinese medicine composition of examples 1-3 in a pre-eclampsia model;
FIG. 4 shows the results of HE staining of kidney tissue (pathological section of kidney tissue) in a mouse model after intervention of the traditional Chinese medicine composition of examples 1-3 in a pre-eclampsia model mouse;
FIG. 5 is a graph showing the results of cell proliferation experiments of HTR-8/SVneo cells treated with different concentrations of atractylenolides I and III;
FIG. 6 is a graph showing the results of cell proliferation experiments of HTR-8/SVneo cells treated with baicalin and baicalein at different concentrations;
FIG. 7 is a graph showing the results of a cell migration experiment under a 200-fold microscope after HTR-8/SVneo cells were treated with the Chinese medicinal composition of example 4;
FIG. 8 is a graph showing the results of cell migration experiments under 200-fold microscope after HTR-8/SVneo cells were repeatedly treated with the Chinese medicinal composition of example 4.
Detailed Description
The present application will be further illustrated by the following examples, but the present application is not limited to these specific embodiments.
Traditional Chinese medicine composition of examples 1-3
The traditional Chinese medicine composition of example 1 comprises the following raw materials: 7.8g of radix scutellariae (water extraction, extraction ratio is 20:1, 390mg of radix scutellariae extract is obtained), 13g of rhizoma atractylodis macrocephalae (water extraction, extraction ratio is 20:1, 650mg of rhizoma atractylodis macrocephalae extract is obtained), and the mass ratio of radix scutellariae to rhizoma atractylodis macrocephalae is 0.6:1;
the traditional Chinese medicine composition of example 2 comprises the following raw materials: 11.7g of radix scutellariae (water extraction, extraction ratio is 20:1, 585mg of radix scutellariae extract is obtained), 16.25g of rhizoma atractylodis macrocephalae (water extraction, extraction ratio is 20:1, 812.5mg of rhizoma atractylodis macrocephalae extract is obtained), and the mass ratio of radix scutellariae to rhizoma atractylodis macrocephalae is 0.75:1;
the traditional Chinese medicine composition of example 3 comprises the following raw materials: 15.62g of radix scutellariae (water extraction, extraction ratio is 20:1, 781mg of radix scutellariae extract) and 19.5g of rhizoma atractylodis macrocephalae (water extraction, extraction ratio is 20:1, 975mg of rhizoma atractylodis macrocephalae extract) 975mg (mass ratio of radix scutellariae to rhizoma atractylodis macrocephalae is 0.8:1).
The traditional Chinese medicine raw materials in the examples 1-3 are respectively fully soaked in 6 times of purified water, decocted for more than 30 minutes at 100 ℃, and filtered by a 2200-mesh filter screen to obtain liquid traditional Chinese medicine extract (decoction).
In an alternative embodiment of the application, the baikal skullcap root and the white atractylodes rhizome raw materials or the water extract are crushed, filtered by a 1200 mesh sieve and mixed according to a certain mass ratio (0.6:1-0.8:1), and the conventional drug carrier can be added, and the granule preparation is obtained through the procedures of granulation and the like.
Traditional Chinese medicine composition of example 4
The traditional Chinese medicine composition of the example 4 comprises the following baicalin in parts by mole: baicalein: the largehead atractylodes lactone I is prepared according to the following ratio of 0.1:0.1: 10.
Experimental example
1. Efficacy of the Chinese medicinal compositions of examples 1-3 on preeclampsia model mouse intervention
(1) Experimental objects
The experiment takes unmatched 7-8 week old female and 8-9 week old male C57BL/6N mice as study subjects, and after the mice are purchased from a company, the mice are fed with the mice and cut off water for 24 hours, and after the mice are fed for 1 week, tail arteries are monitored in a noninvasive manner, and the mice with stable systolic blood pressure and less than 130mm Hg are incorporated into the experiment.
(2) Feeding conditions
All experimental mice are fed into a clean laboratory, the room temperature is 22-24 ℃, the relative humidity is 40-60%, the free diet is adopted, and the illumination time is 8-20 points; noise is less than or equal to 60 dB, ventilation is realized in four seasons, water and food are added every day, and padding is replaced 1 time every week.
(3) Experimental grouping:
all female mice were fed adaptively for 1 week and were monitored for rat tail blood pressure noninvasively, and those with systolic blood pressure stability and less than 130mm Hg were included in the experiment and randomized into:
a control group: 0.35mL of subcutaneous normal saline and 100mg/kg/d of lavage normal saline are administered daily;
model group B: subcutaneous injection of L-NAME (50 mg/kg/d) +100 mg/kg/d of lavage saline was administered daily;
model C + positive drug group: subcutaneous injection of L-NAME (50 mg/kg/d) and administration of gavage aspirin (15.2 mg/kg) were administered daily;
d model + baikal skullcap root and white atractylodes rhizome mixed solution low dose group: subcutaneously injecting L-NAME (50 mg/kg/d) +Gastrodia elata extract 39 mg/kg+Atractylodis rhizoma extract 65mg/kg (Chinese medicinal composition of example 1);
dose group in E model+Baical skullcap root and largehead atractylodes rhizome mixed solution: subcutaneously injecting L-NAME (50 mg/kg/d) +58.5 mg/kg of the extract of Scutellaria baicalensis Georgi and 81.25mg/kg of the extract of Atractylodes macrocephala koidz (Chinese medicinal composition of example 2);
f model + baikal skullcap root and white atractylodes rhizome mixed solution high dose group: subcutaneously injecting L-NAME (50 mg/kg/d) +78 mg/kg of the extract of Scutellaria baicalensis Georgi and 97.5mg/kg of the extract of Atractylodes macrocephala (Chinese medicinal composition of example 3);
8 in each group.
(4) Test procedure
(1) The estrus cycle of the female mice was observed, the female mice in the pre-estrus stage were caged with the male mice (2:1), and the female mice vaginal suppositories were observed 7 the next morning and were noted as GD0 (day 0 of gestation).
(2) At GD0, A, B group is subjected to 100mg/kg/D of normal saline and is subjected to gastric lavage, C group is subjected to aspirin and is subjected to gastric lavage, D group is subjected to low-dose group of mixed solution of scutellaria baicalensis and bighead atractylodes rhizome and is subjected to gastric lavage, E group is subjected to gastric lavage, F group is subjected to high-dose group of mixed solution of scutellaria baicalensis and bighead atractylodes rhizome, and then the stomach is irrigated every day until GD17 is over for pregnancy.
(3) Wherein, at GD8, group A mice are injected with 10 mug/kg/d physiological saline and group B, C, D, E, F mice are injected with L-NAME dissolved by physiological saline until GD17 ends gestation;
(4) meanwhile, urine is reserved at GD7 and GD17 for 24 hours to detect urine protein;
(5) blood pressure was measured once before administration and before the end of pregnancy. Before pregnancy, euthanizing the mice, taking eyeball blood, taking placenta, kidney and liver tissues, measuring the weight and the hip length of the fetal mice, and taking placenta to measure the weight;
(6) paraffin embedding slice and HE staining are carried out on the placenta and kidney of the patient, and morphological changes of baikal skullcap root and largehead atractylodes rhizome medicine on tissues under intervention are observed; immunofluorescence staining is carried out on the tissue slice, and the spatial distribution condition of each factor in the tissue is observed;
(7) RNA and protein are then extracted for QPCR and WB, and differentiation analysis is performed on the genes of Flt1, plgf, hmox-1, nos3, mmp9, IL-6, etc.
Mice were euthanized at GD17 (day 17 of gestation), process blood pressure was monitored, and pre-and post-dose GD7 and GD14 blood pressure was measured, with the result that the mouse model had been successfully replicated and drug treatment was successful.
(5) Results
The shrink compaction test results are shown in figure 1. As can be seen from the results of FIG. 1, after administration of L-NAME and the Chinese medicinal compositions of examples 1-3 (combination of extracts of Baicalein and Baicalein), the "model group" was significantly increased in comparison to the "control group" blood pressure at GD14, and the "model group" was significantly decreased in comparison to the "model group" after treatment with the Chinese medicinal compositions of examples 1-3 (low dose group, medium dose group and high dose group).
Urine protein detection results are shown in FIG. 2. As can be seen from the results of FIG. 2, the Chinese medicinal compositions of examples 1-3 were injected with the nitric oxide synthase inhibitor and then lavaged at GD7, and the urine protein content was measured at GD17 in 24 hours for each group; the "model group" showed a significant increase in urine protein compared to the "control group" and the urine protein content was significantly decreased and significantly different after the treatment with the Chinese medicinal compositions of examples 1 to 3 (low dose group, medium dose group and high dose group).
The results of placenta pathological section are shown in fig. 3, wherein, the 3A picture is a control group: the cells in the placental tissue of the mice were structurally intact. 3B pictures are model group (LNAME): placental tissue placental labyrinthine trophoblast hyperplasia, microthrombosis, villous interstitial edema with erythropenia, giant cell trophoblast hyperplasia and deep labyrinthine trophoblast, spongy trophoblast vacuolated cell islands increase, and thickening of the basal band. CDEF pictures are respectively a positive medicine group (aspirin), a high-dose group, a medium-dose group and a low-dose group, so that the proliferation of placenta tissue placenta labyrinthine trophoblast cells is light, and the vacuolated cell islands of the sponge trophoblast are relieved; the results of FIG. 3 demonstrate that Baicalein can alleviate placenta tissue damage in a pre-eclampsia intervention mouse model.
The results of kidney pathology are shown in fig. 4.
Wherein A is a control group: the kidney tissue surface envelope is composed of dense connective tissue with uniform thickness; kidney essence is superficial cortex and deep medulla, and the cortex medulla demarcation is obvious; the glomeruli in the cortex are uniformly distributed, the cell number in the glomeruli and the matrix are uniform, the tubular epithelial cells are round and full, the brush-shaped edges are orderly and regularly arranged, and the medulla is not obviously abnormal; connective tissue between urinary tubules is renal interstitium, and the interstitium has no obvious hyperplasia; no significant inflammatory changes were seen.
B is a model group: the glomerular stroma is increased in greater quantity in the renal cortex, the cytoplasms are pale, the glomerulus is swollen, partial glomerulus is atrophic, the cell necrosis occurs, and the vacuolation of the renal tubule is serious.
DEF is an experimental group (high, medium, low, respectively) with all of the above changes improved, with the high dose group being most pronounced.
The C positive medicine group also has improvement, and partial inflammatory cell infiltration appears around glomerulus.
The results of FIG. 4 show that Baicalein has protective effect on kidney tissue injury in the intervention of preeclampsia mice model.
The experimental results of the efficacy effect of the traditional Chinese medicine composition of the above examples 1-3 on preeclampsia model mouse intervention demonstrate the potential preventive or therapeutic effect of the combination of baikal skullcap root and white atractylodes rhizome (the combination of extracts) on preeclampsia.
Accordingly, the inventors have conducted further studies to verify the promotion of the active ingredients of baikal skullcap root (baicalein, baicalin) and white atractylodes rhizome (atractylenolide I, atractylenolide III) on the invasion and migration of placental trophoblast cells, respectively, see the following second section.
2. Cell level verification of promotion of active ingredients of Baikal skullcap root and largehead atractylodes rhizome on invasion and migration of placenta trophoblast cells
The specific experimental operation is as follows:
(1) Cell passage
Observing the growth condition of the cells under a microscope, sucking the supernatant after the cells grow to about 90%, and washing twice with PBS;
adding 500 mu L of pancreatin for digestion, and when the cell morphology becomes round under observation of a microscope, adding 2mL of 1640 complete culture solution for stopping digestion; gently blowing for several times by using a pipette until the cells completely fall off from the bottom of the bottle, transferring the cell suspension into a 15mL centrifuge tube, centrifuging at 1000rmp/min and 4 ℃ for 5min; after the supernatant was aspirated, 1640 complete broth was added to mix the cells well and transferred to a new flask in a 1:3 ratio for continued culture.
(2) Cell cryopreservation
When the cells grow to the logarithmic phase, sucking the culture solution, and washing twice with PBS; adding 500 mu L of pancreatin for digestion, observing under a microscope when the cell morphology becomes round, adding 2mL of DMEM complete culture solution for stopping digestion, and completely blowing off the bottle bottom cells by using a pipette; collecting cell suspension, centrifuging at 4deg.C for 5min at 1000 rmp/min; after the supernatant was aspirated, 1mL of cell cryopreservation solution (900. Mu. LFBS+100. Mu.L DMSO) was added to resuspend the cells; transferring the cell suspension to a cell freezing tube, placing the cell suspension in a cell gradient cooling freezing box, and transferring the cell suspension to a liquid nitrogen tank for preservation after overnight at-80 ℃.
(3) Cell proliferation assay
Taking HTR-8/SVneo cells in logarithmic growth phase, digesting with 0.25% trypsin, blowing into single cell suspension, and adjusting cell density to 1×10 4 Inoculating to 96-well culture plate with 100 μl of culture medium, culturing for 24 hr until the cells adhere well, gently sucking the original culture solution, blowing the cells uniformly, and spreading in 96-well plate with uniform density overnight to adhere. Wherein the blank group is cell-free culture medium, the control group is cell-free culture medium, and newly prepared standard medicines, namely baicalin, baicalein, atractylenolide I and atractylenolide III are respectively added in the experiment group. Wherein the baicalin and baicalein have 7 concentrations, each concentration has 4 compound holes, and the atractylenolide I and atractylenolide III have 5 concentrations, and CO is 5% at 37deg.C 2 Culturing under saturated humidity for 24 hr, adding 10 μl of cck8 solution into each well, incubating at 37deg.C for 2 hr, stopping culturing, selecting 450nm wavelength, measuring absorbance (A) of each well on enzyme labeling instrument, recording results with blank control Kong Diaoling, and calculatingGrowth Inhibition (IR). Cell viability = (OD experimental group-blank)/(OD control group-blank) ×100%.
(4) Cell scratch assay
After HTR-8/SVneo cells grow to the logarithmic phase, the culture solution is sucked off and washed 2 times with PBS; after digestion with pancreatin for about 1min, 5mL of complete culture solution was added to terminate digestion, and the bottom cells of the dish were completely blown off with a pipette; transferring the cell suspension into a 15mL centrifuge tube, centrifuging at the temperature of 4 ℃ for 3min at 1000 rmp/min; the supernatant was aspirated, the cells were resuspended in complete culture medium and plated into 6-well plates; when the cell density reaches about 70%, the culture solution is sucked, washed for 2 times by PBS, and then replaced by 1640 culture solution without serum for starving overnight; the next day, when the cells in the 6-well plate form a single cell layer, a sterile 10 mu L gun head is used for uniformly streaking in the culture plate hole, and PBS is used for washing for 2 times to remove the detached cells; then adding 1640 culture solution containing 2% PBS, and adding baicalin, baicalein, atractylenolide I and atractylenolide III with different concentrations into each hole, and photographing scratches under a microscope, wherein the scratches are 0 h.
(5) Results
The results of the proliferation experiments of atractylenolides I and III are shown in fig. 5 and 6, respectively. As shown in FIG. 5, after treatment with different doses (0.01. Mu.M-20. Mu.M) of atractylenolide I, the proliferation rate of human chorionic trophoblast cells increased with increasing atractylenolide I concentration over a range (increasing continuously 0.01. Mu.M-10. Mu.M); the proliferation rate of human chorionic trophoblast cells is highest at a drug concentration of 10 mu M, but the proliferation rate is remarkably reduced when the concentration of atractylenolide I is more than 10 mu M. However, as shown in FIG. 6, the proliferation effect of human chorionic trophoblast cells was not obvious under the action of different concentrations of atractylenolide III, and therefore this drug was not used in the experiments thereafter.
The results of the proliferation experiments of baicalin and baicalein are shown in fig. 7 and 8 respectively. As shown in FIGS. 7 and 8, baicalin in the concentration range of 0.001. Mu.M to 1. Mu.M and baicalein in the concentration range of 0.01. Mu.M to 0.5. Mu.M can promote proliferation of human chorionic trophoblast cells as compared with the blank group. The proliferation rate of human chorionic trophoblast is highest when baicalin and baicalein are both at a concentration of 0.1 mu M, and the proliferation rate is reduced when the medicine concentration is more than 0.1 mu M.
As a result of the above-mentioned cell level experiments, the inventors found that the optimal therapeutic doses (drug concentrations) of atractylenolide I, baicalin and baicalein were 10. Mu.M, 0.1. Mu.M and 0.1. Mu.M, respectively. Thus, the inventors tried to combine three medicinal ingredients of atractylenolide I, baicalin, baicalein in optimal concentrations and verify their potential therapeutic effects, see the following third section.
3. Experimental results of the Chinese medicinal composition of example 4 promoting HTR-8/Svneo cell migration
(1) Cell invasion assay
The invasive capacity of the cells was measured using the Transwell cell method. Matrigel is stored at-20deg.C after subpackaging, and is placed at 4deg.C for melting before use, and precooled pipette and gun head are used during operation. Serum-free 1640 medium was used at 1:8 diluting matrigel, adding 30 μl into a Transwell chamber, incubating at 37deg.C for 30min, and adjusting cell density to 2×10 with serum-free culture solution 5 /mL. 200. Mu.L cell suspensions of different doses containing no drug and drug (the Chinese medicinal composition of example 4) were added to the upper chamber according to the grouping condition, 600. Mu.L of 1640 culture solution containing 10% serum was added to the lower chamber, and 5% CO was added at 37 DEG C 2 Culturing for 24 hours under the condition; after 24 hours, the PBS washes the Transwell cell, gently wipes the cells on the upper surface of the upper cell with a cotton swab, inverts and air dries; fixing with 95% ethanol for 20min, air drying, adding 0.1% crystal violet dye solution, placing the cell into the solution, making the lower surface of the cell just contact with the surface of the dye solution, and dyeing for 30min; the lower surface of the chamber was cleaned with double pure water, dried, and randomly picked up under an inverted microscope (x 200 times) for 5 fields, and counted by photographing. Each group was provided with 3 parallel wells and the experiment was repeated 3 times.
Inhibition of invasion = (1-number of experimental wells invading cells/number of control wells invading cells) ×100%.
(2) Results
The experimental results of the traditional Chinese medicine composition of example 4 for promoting HTR-8/Svneo cell migration are shown in FIG. 7 and FIG. 8 (FIG. 8 is the repeated experimental results). As shown in FIGS. 7 and 8, wherein AA ' is HTR-8/Svneo cells treated with a high dose of the Chinese medicinal composition (atractylenolide I10. Mu.M, baicalin 0.1. Mu.M), BB ' is HTR-8/Svneo cells treated with a low dose of the composition (atratylenolide I1. Mu.M, baicalin 0.01. Mu.M), and CC ' is HTR-8/Svneo cells treated with no drug as a control group. In the same field of view, the cell numbers of the images AA ' and BB ' are obviously increased compared with those of the images CC ', and the cell numbers are obviously increased under the observation of a 200-time microscope, namely, the cell migration capacity of the experimental group treated by the compositions with different doses is obviously improved.
The results were reproducible and the composition of example 4, at a range of concentrations, promoted migration of HTR-8/Svneo cells, demonstrating the efficacy of the composition of example 4 in the treatment and prevention of preeclampsia.
It should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is for clarity only, and that the skilled artisan should recognize that the embodiments may be combined as appropriate to form other embodiments that will be understood by those skilled in the art.
The above list of detailed descriptions is only specific to practical embodiments of the present application, and they are not intended to limit the scope of the present application, and all equivalent embodiments or modifications that do not depart from the spirit of the present application should be included in the scope of the present application.
Claims (8)
1. A Chinese medicinal composition is characterized in that: the traditional Chinese medicine composition comprises a baical skullcap root extract and a largehead atractylodes rhizome extract, wherein the mass ratio of the baical skullcap root extract to the largehead atractylodes rhizome extract is 0.6-0.8: 1.
2. the traditional Chinese medicine composition according to claim 1, wherein: the traditional Chinese medicine composition is in the form of decoction, tablets, capsules or granules.
3. The use of a Chinese medicinal composition according to claim 1 or 2 for the preparation of a medicament for the prophylaxis and/or treatment of preeclampsia.
4. A Chinese medicinal composition is characterized in that: the traditional Chinese medicine composition comprises baicalin, baicalein and atractylenolide I.
5. The traditional Chinese medicine composition according to claim 4, wherein: according to the mole parts, the content of baicalin is 0.001-1 part, the content of baicalein is 0.01-0.5 part, and the content of atractylenolide I is 1-20 parts.
6. The traditional Chinese medicine composition according to claim 5, wherein: according to the mole parts, the content of baicalin is 0.1 part, the content of baicalein is 0.1 part, and the content of atractylenolide I is 10 parts.
7. The traditional Chinese medicine composition according to any one of claims 4 to 6, characterized in that: the traditional Chinese medicine composition is in the form of decoction, tablets, capsules or granules.
8. The use of a Chinese medicinal composition according to any one of claims 4 to 7 for the preparation of a medicament for the prophylaxis and/or treatment of preeclampsia.
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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 |
| CN104491003A (en) * | 2015-01-23 | 2015-04-08 | 天津市南开医院 | Jiawei Yupingfeng gel, preparation method and purpose thereof |
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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 |
| CN104491003A (en) * | 2015-01-23 | 2015-04-08 | 天津市南开医院 | Jiawei Yupingfeng gel, preparation method and purpose thereof |
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Inventor after: Li Jie Inventor after: Sun Shujun Inventor after: Liu Yong Inventor before: Sun Shujun Inventor before: Li Jie Inventor before: Liu Yong |