CN115998730A - Application of Chinese angelica effective component in ischemic stroke treatment medicine - Google Patents

Abstract

The invention discloses an application of angelica effective component in the medical biotechnology field in ischemic stroke treatment medicine, wherein the composition used by bone marrow mesenchymal stem cells and angelica effective component is SF.BP.MSCs composition, the SF.BP.MSCs composition is a medicine for accelerating differentiation and migration of bone marrow mesenchymal stem cells and enhancing angiogenesis and neurogenesis as pharmacological actions, and the SF.BP.MSCs composition comprises 60mg/kgSF, 10mg/kgBP and 2 multiplied by 10 ⁶ And each of the mesenchymal stem cells. The combination of bone marrow mesenchymal stem cells and radix Angelicae sinensis effective components can induce bone marrow mesenchymal stem cellsMigration and differentiation, reduced infarct volume, enhanced angiogenesis and neurogenesis.

Description

Application of Chinese angelica effective component in ischemic stroke treatment medicine

Technical Field

The invention belongs to the technical field of medical biology, and particularly relates to application of an active ingredient of angelica sinensis in a medicament for treating ischemic stroke.

Background

Ischemic stroke is a brain tissue necrotic disease in which a large number of neurons in the central area and penumbra of ischemia undergo necrosis and apoptosis due to arterial thrombosis blocking blood flow, resulting in attenuation of nerve function, and is a major type of cerebrovascular disease. Related data indicate that the second leading cause of death and the leading cause of disability worldwide during stroke, due to the strong burst of such diseases, need to be discovered and therapeutic measures taken in time.

In recent years, cell therapy has been advanced in medicine, and research has shown that Mesenchymal Stem Cells (MSCs) are capable of differentiating into neuronal cells and replacing damaged neurons after cerebral ischemia, and activating endogenous restorative responses (such as neurogenesis, angiogenesis, synaptogenesis, etc.) against damaged brain.

Based on the directional transplantation treatment of the bone marrow mesenchymal stem cells, the research proves that the effect of the combined treatment of the bone marrow mesenchymal stem cells and the medicaments on stroke is superior to that of the single bone marrow mesenchymal stem cell treatment or the medicament treatment, for example, simvastatin combined with MSCs can obviously activate astrocytes, increase the expression of astrocyte-derived stromal cell derived factor-1 alpha (SDF-1 alpha), vascular Endothelial Growth Factor (VEGF), brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) in the hypoxia-deficient astrocytes, and up-regulate the Akt/mammalian rapamycin target protein (mTOR) signaling pathway 21.

Along with the direction of the combined therapeutic medicine turning to traditional Chinese medicines, the joint application of astragaloside, naomai Yi capsule, buyang Huanwu decoction, tongxin luo and marrow mesenchymal stem cells can obviously promote angiogenesis and relieve ischemic injury, but the angelica is one of cardiovascular and cerebrovascular therapeutic medicines, and no related research on the aspect of ischemic stroke by the combination of the active ingredients of the angelica and the marrow mesenchymal stem cells is available at present, so that the application of the active ingredients of the angelica in the therapeutic medicine of ischemic stroke is proposed.

Disclosure of Invention

In order to solve the problem that no drug for treating ischemic stroke by combining the active ingredients of angelica and bone marrow mesenchymal stem cells is applied, the invention aims to provide the application of the active ingredients of angelica in the drug for treating ischemic stroke.

In order to achieve the above object, the technical scheme of the present invention is as follows: the application of the angelica effective component in the medicine for treating ischemic stroke, and the combined use of the bone marrow mesenchymal stem cells and the angelica effective component induces the migration and differentiation of the bone marrow mesenchymal stem cells, and reduces the infarct volume.

Further, the effective cost of angelica comprises n-butylphthalide BP and sodium ferulate SF.

Further, the composition used by combining the bone marrow mesenchymal stem cells and the active ingredients of Chinese angelica is SF.BP.MSCs composition.

Further, SF, BP, MSCs compositions are pharmacological agents that accelerate differentiation and migration of bone marrow mesenchymal stem cells and enhance angiogenesis and neurogenesis.

Further, the SF.BP.MSCs composition includes 60mg/kg SF, 10mg/kg BP and 2X 10 ⁶ And each of the mesenchymal stem cells.

Further, the preparation method of the SF, BP and MSCs composition is as follows:

s1, extracting mesenchymal stem cells from a femur or tibia region;

s2, extracting n-butylphthalide BP and ferulic acid FA from angelica, and preparing sodium ferulate SF from the ferulic acid FA;

s3, mixing n-butylphthalide BP, sodium ferulate SF and bone marrow mesenchymal stem cells to prepare an injection liquid preparation.

Further, in S1, bone marrow mesenchymal stem cells are extracted from the femur or tibia region by a total bone marrow adherence method.

Further, the step of extracting the effective components of the angelica in the step S2 is specifically as follows:

s21, slicing and grinding Chinese angelica, adding water for cooking, filtering and concentrating Chinese angelica cooking liquid;

s22, adding ethanol into the concentrated liquid to extract the crude extract of the active ingredients of the angelica;

s23, washing a column with petroleum ether with the mass times of 1-2 and the mass times of 10-20 in sequence, and filtering to obtain an angelica active ingredient extract, wherein the angelica active ingredient extract comprises n-butylphthalide BP and ferulic acid FA;

s24, preparing sodium ferulate SF from the ferulic acid by adopting an alkaline hydrolysis method.

After the scheme is adopted, the following beneficial effects are realized:

1. the active ingredients in the angelica have the functions of antioxidation and anti-inflammatory, sodium salt of ferulic acid FA-Sodium Ferulate (SF) in the active ingredients can promote the mesenchymal stem cells to express nestin, GFAP and neuron specific class III beta-tubulin (Tuj-1), thereby promoting the differentiation of the mesenchymal stem cells into astrocytes and neuron auspicious cells; meanwhile, compared with single bone marrow mesenchymal stem cell treatment, the migration efficiency of transplanted bone marrow mesenchymal stem cells into a lesion area is low, as the upward dispatch of SDF-1/CXCR4 axis is positively correlated with the migration efficiency of SVZ neuroblast after stroke, n-butylphthalide BP and sodium ferulate SF can be combined with MSCS to up-regulate SDF-1/CXCR4 axis, so that stem/progenitor cells can migrate to an infarct area, thereby improving the defective nerve function of ischemic cerebral apoplexy patients and reducing the infarct volume;

2. the brain-derived neurotrophic molecule BDNF in the neuron-like cells is combined with tropomyosin receptor enzyme B (TrkB) to activate AKT/mTOR signals so as to further up-regulate the expression of Hypoxia Inducible Factor (HIF) -1 alpha, thereby promoting the expression of VEGF and being beneficial to post-stroke angiogenesis and neurogenesis.

Drawings

FIG. 1 is a schematic diagram of an embodiment of the present invention.

Fig. 2 is an MRI diagram of experimental data of an embodiment of the present invention.

Detailed Description

The following is a further detailed description of the embodiments:

an example is substantially as shown in figures 1-2 of the accompanying drawings:

the application of the angelica effective component in the medicine for treating ischemic stroke, and the combined use of the bone marrow mesenchymal stem cells and the angelica effective component induces the migration and differentiation of the bone marrow mesenchymal stem cells, and reduces the infarct volume.

The angelica effective components comprise n-butylphthalide BP and sodium ferulate SF, the composition used by the bone marrow mesenchymal stem cells and the angelica effective components is SF.BP.MSCs composition, and the SF.BP.MSCs composition is a medicament with pharmacological actions of accelerating differentiation and migration of the bone marrow mesenchymal stem cells and enhancing angiogenesis and neurogenesis.

SF.BP.MSCs composition comprising 60mg/kg SF, 10mg/kg BP and 2X 10 ⁶ The preparation method of the mesenchymal stem cells per ml is as follows:

s1, extracting mesenchymal stem cells from a femur or tibia region by a whole bone marrow adherence method;

s2, extracting n-butylphthalide BP and ferulic acid FA from angelica, and preparing sodium ferulate SF from the ferulic acid FA, wherein the method specifically comprises the following steps:

s21, slicing and grinding Chinese angelica, adding water for cooking, filtering and concentrating Chinese angelica cooking liquid;

s22, adding ethanol into the concentrated liquid to extract the crude extract of the active ingredients of the angelica;

s23, washing a column with petroleum ether with the mass times of 1-2 and the mass times of 10-20 in sequence, and filtering to obtain an angelica active ingredient extract, wherein the angelica active ingredient extract comprises n-butylphthalide BP and ferulic acid FA;

s24, preparing sodium ferulate SF from ferulic acid by adopting an alkaline hydrolysis method;

s3, mixing n-butylphthalide BP, sodium ferulate SF and bone marrow mesenchymal stem cells to prepare an injection liquid preparation.

The following are experimental data for this application:

1. the rats to be tested were randomly equally divided into: the rats to be tested are ischemic rats, and the rats to be tested are ischemic rats.

2. Treatment: the experimental group adopts SF.BP.MSCs composition injection in the scheme, the control group 1 adopts MSCs injection, the control group 2 adopts oral angelica extract, and the treatment period is normally fed.

3. And (3) observing the indexes: infarct volume, time to start decreasing infarct volume before and after treatment, as shown in table 1:

TABLE 1 index Chang Table before and after ischemic rat treatment

4. Conclusion: as can be seen from the MRI chart of fig. 2 and the data in table 1, the time for starting to reduce the infarct volume of the rats in the experimental group is earlier than that of the rats in the control group 1 and the control group 2, and the infarct volume of the rats in the experimental group is smaller than that of the rats in the control group 1 and the control group 2 after the treatment, therefore, the bone marrow mesenchymal stem cells proposed by the scheme are used in combination with the active ingredients of angelica sinensis, and can induce the migration and differentiation of the bone marrow mesenchymal stem cells, reduce the infarct volume, and enhance angiogenesis and neurogenesis.

It is noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

The foregoing is merely an embodiment of the present invention, and a specific structure and characteristics of common knowledge in the art, which are well known in the scheme, are not described herein, so that a person of ordinary skill in the art knows all the prior art in the application day or before the priority date of the present invention, and can know all the prior art in the field, and have the capability of applying the conventional experimental means before the date, so that a person of ordinary skill in the art can complete and implement the present embodiment in combination with his own capability in the light of the present application, and some typical known structures or known methods should not be an obstacle for a person of ordinary skill in the art to implement the present application. It should be noted that modifications and improvements can be made by those skilled in the art without departing from the structure of the present invention, and these should also be considered as the scope of the present invention, which does not affect the effect of the implementation of the present invention and the utility of the patent. The protection scope of the present application shall be subject to the content of the claims, and the description of the specific embodiments and the like in the specification can be used for explaining the content of the claims.

Claims (8)

1. The application of the Chinese angelica effective component in the medicament for treating ischemic stroke is characterized in that: the bone marrow mesenchymal stem cells and the Chinese angelica active ingredients are used together to induce the migration and differentiation of the bone marrow mesenchymal stem cells, so as to reduce the infarct volume.

2. The use of an active ingredient of angelica sinensis as claimed in claim 1 for a therapeutic drug for ischemic stroke, characterized in that: the effective cost of angelica comprises n-butylphthalide BP and sodium ferulate SF.

3. The use of an active ingredient of angelica sinensis as claimed in claim 2 for a medicament for treating ischemic stroke, characterized in that: the composition used by combining the bone marrow mesenchymal stem cells and the active ingredients of Chinese angelica is SF.BP.MSCs composition.

4. The use of an active ingredient of angelica sinensis as claimed in claim 3 for a therapeutic drug for ischemic stroke, characterized in that: SF, BP and MSCs are drugs with pharmacological actions of accelerating differentiation and migration of bone marrow mesenchymal stem cells and enhancing angiogenesis and neurogenesis.

5. The use of the active ingredient of angelica sinensis as claimed in claim 4 for treating ischemic stroke, wherein: SF.BP.MSCs composition comprises 60mg/kg SF, 10mg/kg BP and 2X 10 ⁶ And each of the mesenchymal stem cells.

6. The use of the active ingredient of angelica sinensis as claimed in claim 5 for the treatment of ischemic stroke, wherein: the preparation method of the SF, BP and MSCs composition is as follows:

s1, extracting mesenchymal stem cells from a femur or tibia region;

s2, extracting n-butylphthalide BP and ferulic acid FA from angelica, and preparing sodium ferulate SF from the ferulic acid FA;

s3, mixing n-butylphthalide BP, sodium ferulate SF and bone marrow mesenchymal stem cells to prepare an injection liquid preparation.

7. The use of an active ingredient of angelica sinensis as claimed in claim 6 for a therapeutic drug for ischemic stroke, characterized in that: and in the step S1, bone marrow mesenchymal stem cells are extracted from the femur or tibia region by adopting a full marrow adherence method.

8. The use of an active ingredient of angelica sinensis as claimed in claim 7 for a therapeutic drug for ischemic stroke, characterized in that: the effective components of the angelica sinensis extracted in the S2 are specifically as follows:

s21, slicing and grinding Chinese angelica, adding water for cooking, filtering and concentrating Chinese angelica cooking liquid;

s22, adding ethanol into the concentrated liquid to extract the crude extract of the active ingredients of the angelica;

s23, washing a column with petroleum ether with the mass times of 1-2 and the mass times of 10-20 in sequence, and filtering to obtain an angelica active ingredient extract, wherein the angelica active ingredient extract comprises n-butylphthalide BP and ferulic acid FA;

s24, preparing sodium ferulate SF from the ferulic acid by adopting an alkaline hydrolysis method.

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