CN111481533A - Application of ferulic acid in preparation of medicine for treating vascular diseases - Google Patents
Application of ferulic acid in preparation of medicine for treating vascular diseases Download PDFInfo
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- CN111481533A CN111481533A CN202010395578.7A CN202010395578A CN111481533A CN 111481533 A CN111481533 A CN 111481533A CN 202010395578 A CN202010395578 A CN 202010395578A CN 111481533 A CN111481533 A CN 111481533A
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Abstract
The invention belongs to the technical field of medicines, and discloses an application of ferulic acid in preparing a medicine for treating vascular diseases, wherein experiments show that the ferulic acid can effectively expand vasoconstriction caused by endothelin (ET1), has strong blood vessel expansion activity and blood flow increasing effect, especially has obvious curative effect on capillary vessel diameter expansion and capillary vessel injury, can be used for preparing the medicine for treating the vascular diseases, especially the capillary vessel diseases, has wide sources and low price, and has deep development potential.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of ferulic acid in preparation of a medicine for treating vascular diseases.
Background
With the gradual aging stage of China, the incidence of cardiovascular and cerebrovascular diseases is continuously improved, the cardiovascular and cerebrovascular diseases have the characteristics of high incidence, high disability rate, high death rate, high recurrence rate and more complications, and seriously threaten the health of the old, such as the problems of heart failure, respiratory failure, kidney failure and the like caused by improper treatment. In recent years, cardiovascular abnormalities have also been found to be closely related to certain neurodegenerative diseases, such as alzheimer's disease, vascular dementia, parkinson's disease, and the like.
Studies have shown that Endothelin (ET) plays an important role in many cardiovascular and cerebrovascular diseases such as chronic heart failure, hypertension, atherosclerosis, pulmonary hypertension and chronic renal failure. Endothelin is a small molecule bioactive substance discovered and isolated from porcine aorta by japanese scholars in 1988, and has three isoforms: ET-1, ET-2 and ET-3, its expression has different tissue specificities, among them, human ET-1 is mainly expressed in vascular endothelial cell, has very strong vasoconstriction action, at the same time also has the characteristics of promoting cell growth and preferential division, and is the cause of several diseases. To inhibit the action of endothelin, research and development of endothelin antagonists have become a current focus of research.
A great part of cardiovascular and cerebrovascular problems mainly appear as blood flow reduction, cerebral blood supply insufficiency and the like, so expanding blood vessels to increase blood flow and improving microcirculation are main means for preventing and treating cardiovascular and cerebrovascular diseases, and therefore, finding a component capable of effectively expanding blood vessels to improve blood vessel conditions becomes a technical problem to be solved urgently at present.
Disclosure of Invention
Therefore, the invention aims to solve the technical problems, and provides the application of ferulic acid in preparing a medicament or a health-care product for treating vascular diseases.
In order to solve the technical problems, the technical scheme of the invention is as follows:
the invention provides an application of ferulic acid in preparing a medicament or a health-care product for treating vascular diseases.
Further, the invention provides an application of ferulic acid in preparing a vascular dilation drug or a health product.
Further, the invention provides an application of ferulic acid in preparing a medicament or a health-care product for treating capillary vessel diseases.
Further, the medicament comprises one or more pharmaceutically acceptable carriers or excipients.
Further, the medicine is a pharmaceutical preparation mainly prepared from ferulic acid and one or more pharmaceutically acceptable carriers or excipients.
Further, the vascular disease is endothelin-induced vasoconstriction.
Further, the medicine is one of tablets, injections or granules.
Compared with the prior art, the technical scheme of the invention has the following advantages:
experiments show that ferulic acid can effectively dilate vasoconstriction caused by endothelin (ET1), has strong vasodilation activity and blood flow increasing effect, particularly has obvious curative effect on capillary diameter dilation, can be used for preparing medicines or health products for treating vascular diseases, particularly capillary diseases, has wide sources and low price, has small side effect and has deep development potential.
Drawings
In order that the present disclosure may be more readily and clearly understood, reference is now made to the following detailed description of the embodiments of the present disclosure taken in conjunction with the accompanying drawings, in which
FIG. 1 is a photograph of control stained brain slices in example 3 of the present invention;
FIG. 2 is a drawing of a stained brain slice of the administration group in example 3 of the present invention.
Detailed Description
In order that the present disclosure may be more readily and clearly understood, reference will now be made in detail to the present disclosure, examples of which are illustrated in the accompanying drawings.
Example 1
The embodiment provides an application of ferulic acid in preparing a medicament for treating vascular diseases, in particular an application of ferulic acid in preparing a medicament for treating vasoconstriction diseases caused by endothelin (ET 1).
Dilating action of ferulic acid on vasoconstriction caused by endothelin (ET1)
1. Laboratory animal
The experiment adopts male C57B L/6 mice (purchased from Kunming medical university animal center) with the weight of about 20 g, the animals are raised in Kunming animal research institute experimental animal center, the indoor temperature is controlled at 24 +/-2 ℃, the circadian rhythm is 12/12 hours (day/night), the mice can drink water by free diet, and all animal operations meet the requirements of the national committee of the Kunming animal research institute of Chinese academy of sciences.
2. Jugular vein laser speckle blood flow detection
The laser speckle blood flow instrument (Riwold, Shenzhen, China) is used for detecting blood flow in experiments, after a mouse is subjected to deep anesthesia by injecting pentobarbital sodium into an abdominal cavity of the mouse (80mg/kg), the skin of a neck is incised, subcutaneous connective tissues are exposed, the cervical veins (with slight pulsation and the diameter of 2-4 mm) are slowly separated in a blunt manner layer by layer until the cervical veins are seen (with slight pulsation) and are placed under a lens of the laser speckle blood flow instrument, physiological saline (100 mu l) is dripped into the cervical veins, a baseline is recorded for 5 minutes, then the physiological saline is sucked away by a cotton ball, endothelin (1 mu g/ml,100 mu l) is dripped, 10 minutes are recorded, and ferulic acid (2mg/ml,100 mu l) or the physiological saline (100 mu l) is sucked away by the endothelin. The average blood flow in the first 5 minutes was taken as a baseline (normalized by the baseline blood flow), and the blood flow 10 minutes after the addition of endothelin was compared with the blood flow 10 minutes after the addition of ferulic acid or physiological saline.
Data statistical analysis: the data statistics and analysis adopts Graph Pad Prism 7 software, and the experimental data analysis method comprises the following steps: and (5) carrying out t test on independent samples. The results are shown as mean ± SEM, with significant differences set at P <0.05 as significant differences, and the test results are shown in table 1.
TABLE 1 Ferulic acid can dilate endothelin (ET1) induced vasoconstriction
The experimental data show that strong vasoconstriction is caused after the endothelin is dripped into the jugular vein of the mouse, and the blood flow is reduced by about 40 percent after 10 minutes. Then absorbing endothelin and dripping ferulic acid or normal saline, recording for 10 minutes, and finding that dripping ferulic acid obviously increases blood flow by 20%, and dripping normal saline has no obvious change in blood flow. The experimental results show that ferulic acid can expand vasoconstriction caused by endothelin (ET1) and has strong vasodilation activity.
Experiments show that the ferulic acid can be used for preparing a vascular dilation medicament or a health-care product, the medicament comprises the ferulic acid and one or more pharmaceutically acceptable carriers or excipients, the pharmaceutically acceptable carriers refer to pharmaceutically acceptable substances, compositions or carriers, such as liquid or solid fillers, diluents, excipients, solvents and the like, and the medicament can be tablets, injections or granules, and can also be preparations such as dropping pills, powder syrups and the like.
Example 2
Intraperitoneal ferulaic acid administration can increase cerebral blood flow under physiological state of Alzheimer disease model mice (APP/PS1 mice)
1. Laboratory animal
A6-month-old male APP/PS1 double transgenic mouse ((B6.Cg-Tg (APPsw, PSEN1dE9) 85 Dbo/Mmjax; Jackson lab, purchased at Nanjing university model animal center) and its littermate negative control mouse APP/PS1 mouse expresses mutant human amyloid precursor protein (APPsw) and human presenilin (DeltaE 9). The mouse forms β amyloid precipitates in the brain at 6-7 months of age.animal is housed in Kunming institute laboratory animal center independent ventilated system cages (IVC), the indoor temperature is controlled at 24 + -2 ℃, the circadian rhythm is 12/12 hours (day/night), and the animal can freely drink water.
2. Experimental methods
The experiment used a laser speckle blood flow meter to detect changes in cerebral blood flow of (Riwonder, Shenzhen, China) mice. First, the mice were respiratory anesthetized with 1% isoflurane (revold, shenzhen, china), the animals were placed in the mouse stereotaxic apparatus (revold, shenzhen, china), and the animal body temperature was maintained at 37 ± 0.5 ℃ by a small animal temperature-controlled heating pad. The hair of the head was shaved with a shaver, then the scalp was subcutaneously injected with procaine for local anesthesia, the scalp was longitudinally incised with a scalpel, the skull was exposed and cleaned with physiological saline, and the skull was kept moist by dropping sterile physiological saline. Then the mouse brain is placed under a laser speckle blood flow instrument microscope and laser, the focal length is adjusted to the best definition, a fixed area is selected according to grid coordinates, a scalp needle head is pre-embedded in the mouse abdominal cavity, and the injection tube is fixed by an adhesive tape. Recording a baseline for 10 minutes under physiological conditions, injecting ferulic acid (alatin, shanghai, china) or solvent control into the abdominal cavity through an embedded needle, and recording for 50 minutes, wherein the body temperature of the mouse is kept constant and the breathing is stable in the whole recording process. The change in cerebral blood flow of the mice was recorded.
Data statistical analysis: the data statistics and analysis adopts Graph Pad Prism 7 software, and the experimental data analysis method comprises the following steps: tukey's multiple comparisons after repeated measures of ANOVA showed mean + -SEM with significant differences set at P <0.05 as significant differences, and the experimental results are shown in Table 2.
TABLE 2 intraperitoneal administration of ferulic acid to increase cerebral blood flow in APP/PS1 mice
The experimental results show that compared with a solvent control group (0mg/kg), the intraperitoneal administration of 10 mg/kg-dose ferulic acid can obviously increase the cerebral blood flow of APP/PS1 mice (P is less than 0.05), and the intraperitoneal injection of 40 mg/kg-dose ferulic acid has a stronger blood flow increasing effect (P is less than 0.001). Intraperitoneal ferulate administration significantly increased cerebral blood flow in APP/PS1 mice and exhibited a dose effect, with blood flow significantly increased and maintained for 50 to 60 minutes after 10 minutes of administration.
Example 3
The embodiment provides an application of ferulic acid in preparing a medicament for treating capillary vessel diseases, in particular to an application of ferulic acid as a vasoactive substance in improving the problem of capillary vessel injury.
1. Laboratory animal
The method is characterized in that a 6-month-old male APP/PS1 double-transgenic mouse ((B6.Cg-Tg (APPsw, PSEN1dE9) 85 Dbo/Mmjax; Jackson lab, purchased from Nanjing university model animal center) and a littermate negative control mouse are adopted, the animal is raised in an independent ventilation system cage (IVC) of Kunming animal institute laboratory animal center, the indoor temperature is controlled at 24 +/-2 ℃, the circadian rhythm is 12/12 hours (day/night), the animal can drink water freely, and all animal operations meet the requirements of the institute of Kunming animal institute of Chinese academy of sciences life ethical committee.
2. Experimental methods
The administration mode comprises the following steps: the medicine is administered by drinking water, and the concentration of the medicine is 20 mg/kg/day. 6-month-old APP/PS1 mice were randomly divided into 2 groups, an administration group (APP/PS1-FA) and a normal drinking group (control group APP/PS1), and the body weight and daily drinking amount of the mice were measured 3 days before administration, and drugs (20 mg/kg/day) were formulated according to the body weight and drinking amount. The drinking bottle is placed on a mouse cage, black plastic paper is wrapped to prevent light, and the water bottle is replaced twice a week. APP/PS1 control and WT mice drink water normally. The administration time is 30 days, 6 months to 7 months of age.
Immunofluorescent staining of animals, which were obtained after one month of administration and subjected to immunofluorescent staining, animals were anesthetized with pentobarbital sodium (8mg/kg), perfused with 0.01M PBS and 4% Paraformaldehyde (PFA), brain tissue was removed, placed in 4% paraformaldehyde and fixed for 24 hours, then placed in 30% sucrose solution for dehydration, after dehydration was completed, coronal sections were taken with a vibrating microtome, the section thickness was 30 um., the same area brain sections were picked up, rinsed with 0.01M PBS for 10 minutes, then incubated with 5% Bovine Serum Albumin (BSA) and 0.3% Triton x100 blocking solution for 1 hour at room temperature, and then incubated overnight at 4 degrees with primary antibody, vascular marker Collagen IV (ab6586,1:500, abcam), antibodies were diluted with 1% Bovine Serum Albumin (BSA) and 0.1% Triton x100, rinsed three times on the next day, incubated with each secondary antibody for 10 minutes, incubated with 1000, L hours at room temperature, and washed with 2 hours of dry tissue sections of the primary antibody, and the sections were stained with a confocal staining slide glass slide, stained with a microscope, stained with a confocal staining solution containing Plzyl (PI) and stained with a 5. A. sections were taken on a confocal microscope.
The images were statistically analyzed by image J, and stained brain slices of experimental mice in the control group and the administration group were obtained, and the stained brain slices are shown in FIGS. 1-2, wherein FIG. 1 is a mouse brain slice of the control group (APP/PS1), and FIG. 2 is an administration group (APP/PS1-FA), and it can be seen that FIG. 2 has a higher blood vessel density and a larger blood vessel diameter.
Data statistical analysis: the data statistics and analysis adopts GraphPad Prism 7 software, and the experimental data analysis method comprises the following steps: the results are shown as mean ± SEM, with significant differences set as P <0.05, the experimental results for mouse hippocampal capillaries are shown in table 3, and the experimental results for mouse cortical capillaries are shown in table 4.
TABLE 3 Effect of ferulic acid treatment on APP/PS1 mouse hippocampal capillaries
TABLE 4 Effect of Ferulic acid treatment on cortical capillaries in APP/PS1 mice
The experimental results show that the capillary density of the hippocampus (Table 3) and the cortex (Table 4) of APP/PS1 mice (APP/PS1-FA) is obviously higher than that of the non-administered group (APP/PS1) (P <0.05) after one month of ferulic acid drinking water treatment, and analysis of capillary diameter shows that the diameter of the hippocampus and the cortex of APP/PS1 mice (APP/PS1-FA) is also obviously higher than that of the non-administered group (APP/PS1) (P < 0.05). In conclusion, the experiment shows that the ferulic acid treatment can obviously increase the density and the diameter of APP/PS1 capillary vessels after one month. Particularly, the drug effect is better when the administration dosage (drinking water administration) is 20mg/kg/day and the drug is continuously administered for one month, and the drug can better expand the diameter of the capillary vessel and improve the damage of the capillary vessel.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (7)
1. The application of ferulic acid in the preparation of medicaments or health-care products for treating vascular diseases.
2. The ferulic acid is used for preparing a blood vessel expanding medicament or a health-care product.
3. The application of ferulic acid in the preparation of medicines or health products for treating capillary vessel diseases is provided.
4. The use of any one of claims 1 to 3, wherein the medicament comprises one or more pharmaceutically acceptable carriers or excipients.
5. The use according to any one of claims 1 to 3, wherein the medicament is a pharmaceutical formulation consisting essentially of ferulic acid and one or more pharmaceutically acceptable carriers or excipients.
6. The use of any one of claims 1 to 3, wherein the vascular disorder is endothelin-induced vasoconstriction.
7. The use according to any one of claims 1 to 3, wherein the medicament is one of a tablet, an injection or a granule.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111035632A (en) * | 2019-12-27 | 2020-04-21 | 天津市肿瘤医院 | Activator of Nrf2 and application of activator in preparation of drugs for preventing and treating environmental toxic substances |
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| CN101219129A (en) * | 2008-01-16 | 2008-07-16 | 浙江大学 | Application of sodium ferulic acid in preparing medicament for expanding vascellum |
| CN102516079A (en) * | 2011-12-13 | 2012-06-27 | 李志强 | Novel ferulic acid derivative, its application and synthetic method |
| CN104958287A (en) * | 2015-05-28 | 2015-10-07 | 四川大学 | Application of ferulic acid derivative as neuroprotective drug |
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- 2020-05-12 CN CN202010395578.7A patent/CN111481533A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1593444A (en) * | 2003-09-10 | 2005-03-16 | 深圳市清华源兴生物医药科技有限公司 | Prescription drug for treating cardiovascular and cerebrovascular diseases |
| CN101219129A (en) * | 2008-01-16 | 2008-07-16 | 浙江大学 | Application of sodium ferulic acid in preparing medicament for expanding vascellum |
| CN102516079A (en) * | 2011-12-13 | 2012-06-27 | 李志强 | Novel ferulic acid derivative, its application and synthetic method |
| CN104958287A (en) * | 2015-05-28 | 2015-10-07 | 四川大学 | Application of ferulic acid derivative as neuroprotective drug |
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| CN111035632A (en) * | 2019-12-27 | 2020-04-21 | 天津市肿瘤医院 | Activator of Nrf2 and application of activator in preparation of drugs for preventing and treating environmental toxic substances |
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Application publication date: 20200804 |