CN115282158A - Application of glucoside compounds - Google Patents

Application of glucoside compounds Download PDF

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CN115282158A
CN115282158A CN202210120146.4A CN202210120146A CN115282158A CN 115282158 A CN115282158 A CN 115282158A CN 202210120146 A CN202210120146 A CN 202210120146A CN 115282158 A CN115282158 A CN 115282158A
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赵筱萍
杨振中
王毅
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Zhejiang Chinese Medicine University ZCMU
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Abstract

The invention relates to an application of glucoside compounds. In particular to application of glucoside compounds in preparing anti-heart failure medicines and health care products for preventing heart failure, the structure of the glucoside compounds is shown as formula (I),
Figure DDA0003496633210000011
in the formula (I), R is alkyl containing 1-6 carbon atoms. The glucoside compound can be used for directly preparingReducing myocardial cell, relieving myocardial fibrosis, improving ejection fraction and left chamber short axis shortening rate, increasing cardiac output, and treating/preventing heart failure.

Description

Application of glucoside compounds
Technical Field
The invention relates to the technical field of pharmaceutical chemistry, in particular to application of glucoside compounds.
Background
Heart failure (Heart failure) is a syndrome caused by abnormal cardiac structure or function, is the terminal stage of the development of various Heart diseases, and has high fatality and disability rate. In the process of occurrence and development of heart failure, myocardial hypertrophy, myocardial fibrosis, ventricular remodeling, reduction of left ventricular short axis shortening rate, reduction of cardiac output and the like can occur. For example, it can improve myocardial cell hypertrophy, relieve myocardial fibrosis, improve ejection fraction and left ventricular short axis shortening rate, and improve cardiac output, and has important effect in relieving heart failure.
At present, clinically, the commonly used drugs for treating heart failure mainly comprise ACE inhibitors, angiotensin II receptor blockers, beta receptor blockers, angiotensin receptors, namely enkephalinase inhibitors, diuretics, digitalis cardiotonic agents and the like. The side effects of these drugs during long-term use cannot be ignored. Researches find that the novel anti-heart failure medicine has important clinical significance for preventing and improving heart failure.
Disclosure of Invention
In view of the above, there is a need to provide a glucoside compound, which can directly reduce the area of myocardial cells, relieve myocardial fibrosis, improve ejection fraction and left ventricular short axis shortening rate, improve cardiac output, and has significant therapeutic/prophylactic effects.
The invention provides an application of glucoside compounds in preparing anti-heart failure drugs, the structure of the glucoside compounds is shown as formula (I),
Figure BDA0003496633190000021
in the formula (I), R is alkyl containing 1-6 carbon atoms.
In one embodiment, the structure of the glucoside compound is shown as formula (I'),
Figure BDA0003496633190000022
in the formula (I'), R is an alkyl group having 1 to 6 carbon atoms.
In one embodiment, R is selected from methyl or ethyl.
In embodiments, the heart failure comprises myocardial hypertrophy, myocardial fibrosis, decreased ejection fraction, decreased left ventricular short axis shortening rate, decreased cardiac output.
In one embodiment, the heart failure comprises induction by at least one of hypertension, aortic stenosis, valvular heart disease, myocarditis, an alpha adrenergic receptor agonist, or a beta adrenergic receptor agonist.
In one embodiment, the drug further comprises an anti-cardiovascular drug combined with the glucoside compound.
In one embodiment, the medicament further comprises a pharmaceutically acceptable carrier.
An application of glucoside compounds in the preparation of health products for preventing heart failure, the glucoside compounds have a structure shown in formula (I),
Figure BDA0003496633190000023
in the formula (I), R is alkyl containing 1-6 carbon atoms.
In one embodiment, the structure of the glucoside compound is shown as formula (I'),
Figure BDA0003496633190000031
in the formula (I'), R is an alkyl group having 1 to 6 carbon atoms.
In one embodiment, R is selected from methyl or ethyl.
The glucose group in the glucoside compound has a synergistic effect with the para-substituted phenyl on the flavone mother nucleus, so that the glucoside compound has an effect of resisting heart failure, and when the glucoside compound is used for preparing a heart failure resisting medicine, the area of myocardial cells can be reduced, myocardial fibrosis is relieved, ejection fraction and left ventricular short axis shortening rate are improved, cardiac output is improved, the progress of the course of disease of heart failure is slowed down, and an excellent treatment effect is achieved; when the glucoside compound is used for preparing a health-care product for preventing heart failure, the glucoside compound can prevent myocardial cell enlargement, relieve myocardial fibrosis, improve ejection fraction and left ventricular minor axis shortening rate, improve cardiac output and has excellent prevention effect.
Drawings
FIG. 1 is a statistical graph of the average area of ventricular myocytes in example 1, wherein M is a model group, A is an formononetin group, B is an formononetin group, C is a calycosin group, and D is a calycosin group;
FIG. 2 is a graph showing the effect of formononetin on the structure and function of the left ventricle of a heart failure model mouse in example 2; in the figure, A is a mouse left ventricle M-type two-dimensional ultrasonic image, B is left ventricle ejection fraction, left ventricle short axis shortening rate and cardiac output, wherein, represents P <0.05, represents P <0.001vs control group, represents P <0.01vs model group, and n =8;
FIG. 3 is the effect of formononetin on the pathological morphological change of myocardial tissue of heart failure mice in example 2, wherein A is the HE and Masson staining pattern of myocardial tissue of mice, B is the volume fraction of myocardial collagen, # represents P <0.05vs control group, # represents P <0.05vs model group, and n =3.
Detailed Description
The application of the glucoside compounds provided by the invention will be further explained below.
The invention provides an application of glucoside compounds in preparing anti-heart failure medicines, the structure of the glucoside compounds is shown as formula (I),
Figure BDA0003496633190000041
in the formula (I), R is alkyl containing 1-6 carbon atoms.
The glucoside compound has a synergistic effect between a glucose group and a phenyl group substituted at the para position on a flavone mother nucleus, so that the glucoside compound has an effect of resisting heart failure.
It is understood that reducing cardiomyocytes specifically means reducing the volume of ventricular myocytes or the area of ventricular myocytes.
In the formula (I), the compound is shown in the specification,
Figure BDA0003496633190000042
represents
Figure BDA0003496633190000043
And/or
Figure BDA0003496633190000044
When the glucoside compound is used for preparing an anti-heart failure drug, the structure of the glucoside compound is preferably as shown in formula (I'),
Figure BDA0003496633190000051
in the formula (I'), R is an alkyl group having 1 to 6 carbon atoms.
In particular, R is an alkyl group containing 1, 2, 3, 4, 5 or 6 carbon atoms, and in one embodiment, the para-substituted phenyl group is preferably coordinated with the glucose group for steric hindrance reduction, said R being selected from methyl or ethyl.
The structure of the glucoside compound is further preferably as shown in a formula (I-A) or a formula (I-B),
Figure BDA0003496633190000052
it is understood that the glucoside compound of formula (I-A) is formononetin, which can also be extracted from Astragalus membranaceus (Astragalus mongholicus Bunge) or Astragalus membranaceus (Astragalus membranaceus Bunge) dried root of Astragalus membranaceus (Astragalus mongholicus Bunge) belonging to Astragalus of Leguminosae.
The ingredients in astragalus membranaceus are very various, mainly saponins, flavonoids, polysaccharides, amino acids and other ingredients, and the pharmacological effects of different ingredients are respectively characterized and difficult to predict, and a large number of experiments are needed to prove. The applicant researches and discovers that the formononetin has the effect of resisting the heart failure, and can be further used for treating or preventing the heart failure.
It can be understood that formononetin can be extracted from astragalus membranaceus, and the method specifically comprises the following steps:
s1, crushing astragalus membranaceus, mixing with a solvent, and performing reflux extraction to obtain an extracting solution;
s2, filtering the extracting solution, separating filtrate and filter residue, concentrating the filtrate to obtain an extraction concentrated solution, suspending the extraction concentrated solution in water, and removing insoluble substances to obtain a sample solution;
s3, adding the sample liquid into a macroporous adsorption resin column, standing to enable the sample liquid to flow out after complete adsorption;
and S4, eluting by using an eluent, collecting an effluent containing the formononetin, concentrating the effluent, and further separating and purifying by using a preparative liquid chromatography to obtain the formononetin.
In order to better extract the formononetin from the astragalus root and to perform the concentration at a lower temperature, in an embodiment, in the step S1, the solvent is ethanol, water or a mixture of ethanol and water.
In order to fully extract the formononetin, the reflux extraction is carried out for 1 to 3 times, and the time for each reflux extraction is 1 to 2 hours; the reflux extraction frequency is preferably 2-3 times, and each time is 1-1.2 h.
It is understood that the source of astragalus root is not particularly limited in the present invention, and is commercially available.
The steps of reflux extraction, filtration and the like are all technical means known to those skilled in the art, and are not particularly limited herein.
In step S3, the present invention does not specifically limit the type of the macroporous adsorbent resin column, and the type of the macroporous adsorbent resin column known to those skilled in the art may be used.
In one embodiment, the standing time is less than or equal to 8 hours, and the flow rate of the sample solution passing through the macroporous adsorption resin column is 0.5 column volume/hour to 3 column volume/hour.
In step S4, in order to ensure the content and purity of formononetin, the step of eluting with an eluent comprises: sequentially carrying out gradient elution by using water, 18-22% ethanol water solution, 35-45% ethanol water solution and 90-95% ethanol water solution; at this time, formononetin is mainly eluted by 35% -45% aqueous ethanol.
In one embodiment, the flow rate of the eluent is from 0.5 column volumes/hour to 3 column volumes/hour, and the amount of each eluent is preferably from 2 column volumes to 6 column volumes.
The concentration of the ethanol aqueous solution is volume fraction, and the loading, elution and collection of the macroporous adsorbent resin are well known to those skilled in the art, and are not particularly limited herein.
In step S4, in order to further ensure the purity of the prepared formononetin, the conditions of the preparative liquid chromatography are preferably: a chromatographic column: agilent Zorbax SB-C18 column (250X 21.2mm,7 μm); mobile phase: the phase A is water, and the phase B is acetonitrile; linear elution gradient: 0min,5% of B;35min,60% B;40min,100% of B;45min,100% by weight B; flow rate: 8mL/min; column temperature: at 30 ℃.
The separation and purification method of preparative liquid chromatography is a technical means well known to those skilled in the art, and the present invention gives only the main parameter conditions, and is not particularly limited herein.
In one embodiment, the heart failure comprises induction by at least one of hypertension, aortic stenosis, valvular heart disease, myocarditis, an alpha adrenergic receptor agonist, or a beta adrenergic receptor agonist. In one embodiment, the alpha adrenergic receptor agonist comprises phenylephrine and the beta adrenergic receptor agonist comprises isoproterenol.
In one embodiment, the drug further comprises an anti-cardiovascular drug combined with the glucoside compound.
In one embodiment, the anti-cardiovascular agent comprises a calcium channel blocker, an angiotensin converting enzyme inhibitor, a beta blocker, a digitalis cardiotonic agent, and the like.
It should be noted that the content of formononetin in the medicament is within the effective therapeutic dose range, and in one embodiment, the medicament further comprises a pharmaceutically acceptable carrier.
The effective therapeutic dose refers to that the mass of the formononetin in the medicine is 0.1mg-1500mg, preferably 10mg-1000mg.
By treatment is meant any treatment of a disease in a mammal, including: preventing the disease, i.e., causing the clinical symptoms of the disease not to develop; inhibiting the disease, i.e., arresting the development of clinical symptoms; and/or, relieving the disease, i.e., causing regression of clinical symptoms.
It is understood that a pharmaceutically acceptable carrier refers to any formulation or carrier vehicle representative of a vehicle capable of delivering an effective amount of an active agent of the present invention, without interfering with the biological activity of the active agent and without toxic side effects to the host or patient, including water, oils, minerals, pastes, lotion bases, ointment bases, and the like. These include suspending agents, viscosity enhancers, skin penetration enhancers, and the like. For additional information on pharmaceutically acceptable carriers, reference may be made to Remington The Science and Practice of Pharmacy,21st Ed, lippincott, williams & Wilkins (2005), the contents of which are incorporated herein by reference.
The medicament is suitable for two administration modes of gastrointestinal administration and parenteral administration, and can be prepared into a gastrointestinal administration preparation and a parenteral administration preparation according to the two administration modes.
The gastrointestinal tract administration preparation comprises tablets, capsules, granules, powder, dripping pills, oral liquid, micro-pills and the like. Among them, tablets, capsules and dripping pills are preferred.
The pharmaceutically acceptable conventional adjuvants in the gastrointestinal tract administration preparation are conventional adjuvants in preparations such as tablet, capsule, granule, powder, dripping pill, oral liquid, pellet, etc. Such as binders including hypromellose, dextrin, polyethylene glycol, syrup, acacia, sorbitol, gelatin, or polyvinylpyrrolidone, etc.; the filler comprises lactose, corn starch, calcium phosphate, sorbitol or glycine, etc.; tabletting lubricants include magnesium stearate, polyethylene glycol, etc.; the disintegrating agent comprises starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose, etc.; wetting agents include sodium lauryl sulfate and the like; the correctant and sweetener comprise stevioside, aspartame, steviosin, xylitol, menthol, and orange essence. The preparation method adopts the conventional preparation method in the field.
Parenteral preparations are mainly injections, including large or small volume injections, sterile powders for injection, and the like. Among them, large or small volume injections are preferable.
The injection is prepared by using the composition and a sterile carrier and adopting a conventional preparation method. When preparing large or small volume injection solution, formononetin suitable for injection production requirement can be dissolved in water for injection, activated carbon is used for adsorption to remove impurities and filtration sterilization is carried out, and then the injection solution is filled into a container for sealing and storage. In order to be suitable for injection use or storage, auxiliary agents commonly used for injection preparations such as preservatives, buffers, pH regulators, osmotic pressure regulators, solubilizers, stabilizers, antioxidants and the like may be added.
The invention also provides an application of the glucoside compound in the preparation of the health care product for preventing the heart failure, the structure of the glucoside compound is shown as the formula (I),
Figure BDA0003496633190000091
in the formula (I), R is alkyl containing 1-6 carbon atoms.
When the glucoside compound is used for preparing the health-care product for preventing the heart failure, the structure of the glucoside compound is preferably shown as a formula (I'),
Figure BDA0003496633190000092
in the formula (I'), R is an alkyl group having 1 to 6 carbon atoms.
In particular, R is an alkyl group containing 1, 2, 3, 4, 5 or 6 carbon atoms, and in one embodiment, in order to reduce steric hindrance, a para-substituted phenyl group is better cooperated with a glucosyl group, and when the glucoside compound is used for preparing a health care product for preventing heart failure, R is selected from methyl or ethyl.
When the glucoside compound is used for preparing the health care product for preventing heart failure, the structure of the glucoside compound is further preferably shown as a formula (I-A) or a formula (I-B),
Figure BDA0003496633190000093
when the glucoside compounds are used for preparing health-care products for preventing heart failure, the types and induction factors of the heart failure refer to the application of the glucoside compounds in preparing medicines for treating the heart failure.
In one embodiment, the health product is in the form of tablet, capsule, granule, oral liquid or dripping pill.
The glucoside compound has the effect of resisting heart failure, can prevent myocardial cell hypertrophy, relieve myocardial fibrosis, improve ejection fraction and left ventricular short axis shortening rate and improve cardiac output when being used for preparing health care products for preventing heart failure, and has excellent prevention effect.
Hereinafter, the application of the glucoside compounds will be further described by the following specific examples.
Preparation example 1
Pulverizing radix astragali, extracting with water under reflux for 2 times (1 hr each time), filtering to remove residue, mixing filtrates, and concentrating the filtrate to obtain concentrated extract.
Suspending the extract concentrated solution in water, removing insoluble substances to obtain a sample liquid, adding the sample liquid into a macroporous adsorption resin column, standing for 2h to ensure that the sample liquid passes through the macroporous adsorption resin column at a flow rate of 2 column volumes/hour after complete adsorption; then, the column was washed with 4 column volumes of water, 4 column volumes of 20% ethanol aqueous solution by volume, 4 column volumes of 40% ethanol aqueous solution by volume, and 4 column volumes of 95% ethanol aqueous solution by volume in this order at flow rates of 2 column volumes/hour.
Separating and collecting chromatographic peak of 27.8min by preparative liquid chromatography, and recovering solvent under reduced pressure to obtain formononetin with purity of 95%; the method comprises extracting and separating formononetin to obtain formononetin, calycosin glycoside and calycosin.
As can be appreciated, formononetin has the structure
Figure BDA0003496633190000101
The calycosin has the structure of
Figure BDA0003496633190000111
Calycosin has the structure of
Figure BDA0003496633190000112
Wherein, the separation conditions of the preparative liquid chromatography are as follows:
the instrument comprises: agilent 1200 preparation of liquid chromatograph fitted with DAD detector.
A chromatographic column: agilent Zorbax SB-C 18 Columns (250X 21.2mm,7 μm).
Mobile phase: phase A is water; and the phase B is acetonitrile.
Linear elution gradient: 0min,5 percent; 35min,60% B;40min,100% by weight B;45min,100% B; flow rate: 8mL/min; column temperature: at 30 ℃.
Preparation example 2
Extracting ventricular myocytes of primary suckling mice: after sterilizing newborn SD suckling mice with 75% alcohol, opening the chest, clipping the heart, placing the heart in a culture dish containing 1% double antibody PBS (phosphate buffer solution), cleaning for many times to remove blood and clipping the redundant tissues such as blood vessels.
The apical part of the heart was excised into an empty petri dish, and the heart of each 10 SD suckling mice was collected. Cutting heart tissue to 1mm 3 Size, add a little PBS containing 1% double antibody (penicillin plus streptomycin), transfer to a 50mL centrifuge tube, and aspirate PBS as much as possible after a little standing.
Adding 2.5mL of digestive juice into a centrifuge tube, placing the centrifuge tube in a shaking table at 37 ℃, shaking at 200rpm for 45min, and blowing and beating the mixture by using a bent pipe for multiple times and uniformly mixing every 15min on average. Digesting until no obvious tissue blocks exist, adding an equal amount of neutralizing solution to stop digestion, uniformly mixing, filtering by a 70-micrometer filter screen, washing the filter screen by using an appropriate amount of neutralizing solution, and collecting filtrate containing cells in a 50mL centrifugal tube.
Centrifuging the centrifuge tube containing filtrate at 4 deg.C for 5min at 600g, discarding supernatant, retaining bottom precipitate, adding high sugar DMEM complete culture solution, suspending cells, mixing, and inoculating to 75cm 2 In a culture flask. And (3) after the culture flask is placed in an incubator and the wall is attached to the wall at a differential speed for 30min, the fibroblasts are attached to the wall in the culture flask, and the rest is ventricular myocyte suspension.
Culturing primary suckling mouse ventricular myocytes: the ventricular myocyte suspension is sucked into a centrifugal tube, 5-bromodeoxyuridine is added to inhibit the growth of the fibroblast, the blank is placed in a constant-temperature incubator to be incubated until the ventricular myocyte is attached to the wall and has spontaneous pulsation, and the blank is used for subsequent experiments.
Example 1
In order to make ventricular myocytes adhere to the wall more stably, 0.5 percent of gelatin is uniformly pre-paved in a 96-hole blackboard in front of a seed plate, and the gelatin is sucked and discarded after 1 hour in an incubator at 37 ℃; ventricular myocytes were seeded at 5000 cells/well in the middle 60 wells of a 96-well black panel, and 100 μ LPBS was added to the remaining wells to avoid edge effects. Placing 96-well blackboard at 37 deg.C and 5% CO 2 And incubating for 48h in the cell culture box.
The blackboard was taken out of 96 wells, the culture solution was discarded, 100. Mu.L of high-glucose DMEM medium containing 0.1% 5-bromodeoxyuridine was added to each well, and the medium was synchronously cultured for 24 hours, and the medium was aspirated off for use.
A model group, an formononetin group, a verbascone group and a verbascone isoflavone group are set up, wherein the model group adds a high-glucose DMEM culture medium containing Phenylephrine (PE) of 100 mu M into a 96-hole blackboard, the formononetin group adds a high-glucose DMEM culture medium containing PE of 100 mu M and formononetin of 50 mu M into the 96-hole blackboard, the verbascone group adds a high-glucose DMEM culture medium containing PE of 100 mu M and isoxanthone of 50 mu M into the 96-hole blackboard, the verbascone group adds a high-glucose DMEM culture medium containing PE of 100 mu M and isoflavonol of 50 mu M into the 96-hole blackboard, and the 96-hole blackboard is respectively placed in a cell culture box for incubation for 48 hours after treatment.
The 96-well blackboard is taken out, the culture solution is respectively sucked off, and PBS is added for rinsing for 3 times and 5 min/time. Add 100. Mu.L paraformaldehyde to each well and fix at room temperature for 20min. Paraformaldehyde is aspirated, and PBS is added for rinsing for 3 times and 5 min/time. 50 μ L of Phalloidin (Alexa Fluor 488 Phalloidin-FITC) labeled ventricular myocyte actin F-actin (1.
After recovering the blotchy phalloidin, 50. Mu.L of Hoechst dye (1. An appropriate amount of PBS was added to each well to maintain cell moistening.
Placing a 96-hole blackboard in
Figure BDA0003496633190000131
Pico personal high content imaging analysis system for automatic acquisition of fluorescence image and use of the analysis system
Figure BDA0003496633190000132
The software performed automated analysis of the pictures and a statistical plot of the average area of the relative ventricular myocytes is shown in figure 1. Relative to the model group, the relative area of the ventricular myocyte in the formononetin group is reduced by 29.31%, and the relative area of the ventricular myocyte in the formononetin group is reduced by 7.04%; the relative area of the myocardial chamber cells in the calycosin glycoside group is reduced by 4.21 percent; the relative area of ventricular myocytes in the calycosin group was reduced by 13.99%.
From the results, it can be seen that formononetin can reduce ventricular myocyte area and slow the progression of myocardial hypertrophy and has excellent therapeutic effects compared with formononetin, calycosin glycoside and calycosin.
Example 2
The formononetin has a protective effect on the heart failure of ISO-induced mice.
1.ISO induced mouse heart failure model establishing and administration method
24 male C57BL/6J mice were randomly divided into a Control group (Control group), a Model group (Model group), and an formononetin group (MBHG group), and 8 mice were each group. Model group and MBHG group were injected with 5mg/kg/d isoproterenol continuously and subcutaneously for 4 weeks to construct mouse heart failure Model, the injection volume was 0.05ml/10g, and control group was injected with 0.9% sodium chloride injection of the same volume subcutaneously. The MBHG group was administered with isoproterenol subcutaneously and 10mg/kg/d of formononetin by intragastric administration, the intragastric volume was 0.2ml/10g, and the control group and Model group were administered with ultrapure water of the same volume by intragastric administration. Mice were weighed once a day and the dosage of isoproterenol and formononetin was adjusted in time to changes in body weight.
2. Echocardiography detection
Removing mouse hair at the left chest part of a mouse, inhaling isoflurane for anesthesia, fixing the mouse hair on an ultrasonic detection table, smearing a proper amount of medical ultrasonic coupling agent at the left heart part, acquiring a cardiac ultrasonogram by using a Vevo ultra-high resolution small animal ultrasonic imaging system, keeping a high-frequency matrix probe at an angle of about 75 degrees with the mouse chest bone, enabling the ultrasonic image to display a left ventricle long axis image of the heart along the direction from a mitral valve to a cardiac apex, randomly selecting 3 continuous cardiac cycles for each mouse to calculate an average value, measuring cardiac function parameters by using Vevo LAB 3.1.0 software, and analyzing the acquired image. The main indicators of cardiac function include: left ventricular Ejection Fraction (EF), cardiac Output (CO), and Left ventricular short axis shortening (FS).
3. Obtaining animal materials
After the administration, the mice were anesthetized, the hearts of 3 mice were used for observation of pathological tissue sections, and the mice were perfused with 0.9% sodium chloride and then with 4% paraformaldehyde, and the hearts of the mice were cut, blood vessels and excess tissues on the heart surface were removed, and the mice were fixed in 4% paraformaldehyde.
4. Histopathological observation
(1) HE staining
And taking out mouse heart tissues fixed in 4% paraformaldehyde for more than 24 hours, treating the tissues by using gradient alcohol to dehydrate, carrying out xylene permeabilization and paraffin embedding, and placing the trimmed wax blocks on a paraffin slicer to slice, wherein the slice thickness is 4 mu m. All sections were HE stained and mounted on neutral gum. The 3 samples per group were photographed using an inverted microscope and the histopathological changes of the heart of the mice in each group were observed at 200x magnification.
(2) Masson staining
Mouse hearts were sectioned in paraffin at a thickness of 4 μm, masson stained, and mounted on neutral gum. Each group of 3 samples was sectioned under an inverted microscope and images were collected to observe the degree of myocardial fibrosis in the cardiac tissue of each group of mice at 200-fold magnification. Randomly selecting 3 visual fields (200 x) in each section, and calculating the Volume Fraction (CVF) of myocardial Collagen as a judgment index of the fibrosis degree of myocardial tissue, wherein the calculation formula is as follows.
CVF = collagen fiber area/total area of myocardium x 100%
5. Effect of formononetin on left ventricle structure and function of heart failure mice
Fig. 2A is a mouse left ventricle M-mode two-dimensional ultrasound image.
Compared with the control group, the left ventricular ejection fraction, the left ventricular short axis shortening rate and the cardiac output of the mice in the model group are all obviously reduced, and after the stomach is irrigated by formononetin, the left ventricular ejection fraction and the left ventricular short axis shortening rate are all obviously improved (figure 2B).
6. Effect of formononetin on myocardial histopathological morphology of heart failure mice
Mouse myocardial tissues were subjected to HE and Masson staining, and pathological changes of the myocardial tissues were observed. The HE staining results show that the myocardial cells of Model group mice are degenerated, necrotic, disorganized, and the extracellular matrix is proliferated, while the myocardial cell damage of MBHG group mice is reduced, and the proliferation of the matrix is not obvious (FIG. 3A). Masson staining results show that collagen fiber proliferation in myocardial tissues of mice in the Model group is remarkably increased compared with that in the Control group, collagen fiber proliferation in myocardial tissues of mice is not remarkable after formononetin gavage, and the CVF is remarkably reduced compared with that in the Model group (figure 3B).
All possible combinations of the technical features of the above embodiments may not be described for the sake of brevity, but should be considered as within the scope of the present disclosure as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is specific and detailed, but not to be understood as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent should be subject to the appended claims.

Claims (10)

1. An application of glucoside compounds in the preparation of anti-heart failure drugs is characterized in that the structure of the glucoside compounds is shown as formula (I),
Figure FDA0003496633180000011
in the formula (I), R is alkyl containing 1-6 carbon atoms.
2. The use of the glucoside compound of claim 1 in the preparation of anti-heart failure medicine, wherein the glucoside compound has a structure shown in formula (I'),
Figure FDA0003496633180000012
in the formula (I'), R is an alkyl group having 1 to 6 carbon atoms.
3. The use of a glucoside compound of claim 2 in the preparation of an anti-heart failure medicament, wherein R is selected from methyl or ethyl.
4. Use of a glucoside compound according to any one of claims 1-3 in the preparation of a medicament for treating heart failure, wherein the heart failure comprises myocardial hypertrophy, myocardial fibrosis, ejection fraction reduction, left ventricular short axis shortening rate reduction, cardiac output reduction.
5. Use of a glucoside compound according to claim 4 in the preparation of a medicament for the treatment of heart failure, wherein the heart failure comprises induction of hypertension, aortic stenosis, valvular disease, myocarditis, alpha adrenergic receptor agonist or beta adrenergic receptor agonist.
6. The use of a glucoside compound of any one of claims 1-3 in the preparation of a medicament for treating heart failure, wherein said medicament further comprises an anti-cardiovascular medicament in combination with said glucoside compound.
7. Use of a glucoside compound according to any one of claims 1-3 in the preparation of a medicament for treating heart failure, wherein the medicament further comprises a pharmaceutically acceptable carrier.
8. An application of glucoside compounds in the preparation of health products for preventing heart failure is characterized in that the structure of the glucoside compounds is shown as formula (I),
Figure FDA0003496633180000021
in the formula (I), R is alkyl containing 1-6 carbon atoms.
9. The application of the glucoside compound in the preparation of the health product for preventing heart failure according to claim 8, wherein the structure of the glucoside compound is shown as formula (I'),
Figure FDA0003496633180000022
in the formula (I'), R is an alkyl group having 1 to 6 carbon atoms.
10. The use of glucosides according to claim 9 in the preparation of a health product for the prevention of heart failure, wherein R is selected from methyl or ethyl.
CN202210120146.4A 2021-07-22 2022-02-07 Application of glucoside compounds Pending CN115282158A (en)

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