Application of codonopsis pilosula polysaccharide in preparation of products for preventing and treating aortic dilatation

Abstract

The invention discloses application of codonopsis pilosula polysaccharide in preparation of a product for preventing and treating aortic dilatation, and the codonopsis pilosula polysaccharide is used for treating the aortic dilatation. The survival rate of aortic dilatation mice can be remarkably increased, aortic dilatation formation is inhibited, collagen deposition in an aortic neutral membrane is reduced, glycosaminoglycan accumulation in the aortic neutral membrane is reduced, and the aortic diameter is reduced. The invention provides a new thought for developing novel drugs for preventing and treating aortic dilatation, and has potential clinical application value and social significance.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of Codonopsis pilosula polysaccharide in the preparation of products for the prevention and treatment of aortic dilation. Background Technology

[0002] Aortic dilatation is a life-threatening condition caused by tears in the aortic intima or intramural hemorrhage, leading to the separation (dilatation) of the aortic wall layers. As blood flows into the aortic wall, the intimal flap can extend forward and backward from the initial tear or hemorrhage site, potentially progressing to collateral arteries. The first two weeks after the onset of aortic dilatation are considered the acute phase, during which patients are highly susceptible to life-threatening complications and death. Treatment methods for aortic dilatation mainly include drug therapy, interventional therapy, and surgical treatment. Although these treatments have made significant progress, the high difficulty of aortic dilatation surgery, postoperative multi-organ dysfunction, and coagulation disorders cannot be completely avoided. Furthermore, postoperative vascular degeneration can lead to further degenerative changes, increasing the risk of secondary surgery and rupture. Therefore, preventive and therapeutic drugs for patients with acute aortic dilatation remain a hot topic in clinical research.

[0003] Codonopsis pilosula, a traditional Chinese medicine, is an important tonic herb belonging to the Campanulaceae family. The medicinal part of Codonopsis pilosula is its dried root, which is mainly produced in China. Its cultivation history can be traced back to ancient times. It is widely used in traditional Chinese medicine as a qi-tonifying herb, commonly used to treat qi deficiency, cough, asthma, and internal heat with thirst. Codonopsis pilosula polysaccharides are one of the core active ingredients extracted from Codonopsis pilosula, possessing anti-tumor, anti-inflammatory, antioxidant, neuroprotective, immune-enhancing, anti-fatigue, and hypoglycemic effects, exhibiting multi-target and multi-pathway regulatory capabilities. According to literature reports, Codonopsis pilosula polysaccharides, as a functional food, can effectively delay cell aging and protect cardiovascular health.

[0004] Currently, there are no literature reports on the use of Codonopsis pilosula polysaccharide in the prevention and treatment of aortic dilatation. Therefore, developing it into a product for the prevention and treatment of aortic dilatation has extremely high potential value and social significance. Summary of the Invention

[0005] In order to better prevent and treat aortic dilatation and fully explore the medicinal value of Codonopsis pilosula, the present invention provides the following technical solution.

[0006] In a first aspect, the present invention provides the use of Codonopsis pilosula polysaccharide in the preparation of products for the prevention and / or treatment of aortic dilatation.

[0007] Preferably, the application includes at least one of the following: (1) Application in the preparation of products that improve survival rate under aortic dilation; (2) Application in the preparation of products that inhibit aortic dilation and / or aortic dissection formation; (3) Application in the preparation of products that reduce collagen deposition in the neutral membrane of the aorta; (4) Application in the preparation of products that reduce the accumulation of glycosaminoglycans in the neutral membrane of the aorta.

[0008] Preferably, the application in the preparation of products that inhibit aortic dilation and / or aortic dissection includes: (2-1) Application in the preparation of products that reduce the diameter of the aorta; (2-2) Application in the preparation of products that reduce the degree of aortic arch dilation.

[0009] Preferably, the aortic dilation is β-aminopropionitrile-induced aortic dilation.

[0010] Preferably, the daily dosage of the Codonopsis pilosula polysaccharide is 8~25 mg / kg, for example: 8, 10, 12, 16, 18, 20, 22, 25 mg / kg.

[0011] Furthermore, the daily dosage of the Codonopsis pilosula polysaccharide is 10-20 mg / kg.

[0012] Preferably, the product is a drug.

[0013] Furthermore, the only active ingredient in the drug is Codonopsis pilosula polysaccharide.

[0014] Furthermore, the dosage forms of the drug include tablets, aqueous injections, powder injections, granules, pills, powders, suppositories, emulsions, gels, aerosols, sprays, powder inhalers, capsules, or oral liquids.

[0015] Furthermore, the routes of administration of the drug include intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, or nebulized administration.

[0016] Preferably, the drug further includes excipients that are permitted to be added to the drug.

[0017] Furthermore, the excipients include isotonic agents, buffer solutions, flavoring agents, excipients, fillers, binders, disintegrants, or lubricants.

[0018] In a second aspect, the present invention provides a method for preventing and / or treating aortic dilatation, comprising the step of administering Codonopsis pilosula polysaccharide to a patient.

[0019] Preferably, the daily dosage of the Codonopsis pilosula polysaccharide is 8~25 mg / kg, for example: 8, 10, 12, 16, 18, 20, 22, 25 mg / kg.

[0020] Furthermore, the daily dosage of the Codonopsis pilosula polysaccharide is 10-20 mg / kg.

[0021] The beneficial effects of this invention are: This invention demonstrates through systematic animal experiments that Codonopsis pilosula polysaccharide can significantly improve the survival rate of mice with β-aminopropionitrile-induced aortic dilatation, inhibit aortic dilatation formation, reduce collagen deposition in the aortic neutral lining, reduce glycosaminoglycan accumulation in the aortic neutral lining, and decrease aortic diameter. This invention provides a new approach for developing novel drugs to prevent and treat β-aminopropionitrile-induced aortic dilatation, offering potential clinical application value and social significance. Attached Figure Description

[0022] Figure 1 The diagram shown is a schematic of the mouse experiment process; Figure 2 The survival curves of mice in each group are shown below. Figure 3 The figure shows the incidence of aortic dilatation and dissection in each group of mice; Figure 4 The results of annular ultrasound examination of the aorta of mice in each group are shown. Figure 5 The figure shows the statistical results of the aortic diameter in each group of mice; Figure 6 The results of staining the microstructure of blood vessels in each group of mice are shown. Figure 7 The results show the statistical results of collagen content, elastic fiber breakage number and glycosaminoglycan content in the neutral membrane of the aorta of mice in each group. Detailed Implementation

[0023] The technical solution of the present invention will be further described below with reference to embodiments and accompanying drawings. The advantages and features of the present invention will become clearer as the description unfolds. However, it should be understood that the embodiments are merely exemplary and do not constitute a limitation on the scope of the present invention.

[0024] It should be noted that, unless otherwise specified, the experimental methods used in the following embodiments are conventional methods in the art. Unless otherwise defined, all scientific and technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art.

[0025] Example 1: Effect of Codonopsis pilosula polysaccharide on aortic dilation in mice 1. Construction of a mouse model of aortic dilation according to Figure 1 The procedure shown was used to construct the mouse model. All animal experiments were conducted in accordance with the guidelines for the use and care of laboratory animals and were approved by the Ethics Committee of China Agricultural University.

[0026] Thirty-six 3-week-old male C57Bl / 6J mice (purchased from Spifort Beijing Biotechnology Co., Ltd.) were randomly divided into three groups: a control group, a BAPN group, and a Codonopsis pilosula polysaccharide intervention group. The control group was fed a normal diet for 25 consecutive days, while the BAPN (β-aminopropionitrile) group and the Codonopsis pilosula polysaccharide intervention group were fed a diet containing 0.4% BAPN for 25 consecutive days to establish an aortic dilation model.

[0027] 2. Codonopsis pilosula polysaccharide administration to mice Mice in the Codonopsis pilosula polysaccharide intervention group were administered 200 mg / kg / day of Codonopsis pilosula polysaccharide by gavage for 25 days. During the administration period, mouse weight and mortality were recorded. On day 25 after the administration period, mice were sacrificed, and their vascular diameters were measured. After dissection, the formation of aortic dilation was observed, and the morbidity rate was recorded. Codonopsis pilosula polysaccharide was purchased from Beijing Kangruina Biotechnology Co., Ltd.

[0028] 3. Mouse ultrasound imaging The maximum diameter of the ascending aorta in mice was assessed by transthoracic echocardiography using a Vevo2100 high-resolution imaging system (FUJIFILM VisualSonics, Toronto, Canada) equipped with an 18-38 MHz scanning head (MS400, mouse cardiovascular). Mice were anesthetized with isoflurane (1-2% oxygen) and kept in a supine position on a temperature-controlled platform. Two-dimensional (B-mode) and M-mode images were used to visualize the ascending aorta and aortic arch. The aortic diameter was measured at end-diastole as an indicator of the severity of aortic dissection. All measurements were averaged over three consecutive cardiac cycles and analyzed by an investigator unaware of the experimental group's condition.

[0029] 4. Histological analysis After euthanasia of mice, aortic tissue was carefully harvested, fixed in 4% paraformaldehyde, dehydrated serially with graded ethanol, and embedded in paraffin. Serial transverse sections (5 μm thick) were prepared for histological evaluation. Massen's trichrome staining was performed to assess collagen deposition and overall tissue structure. Elastica van Gieson (EVG) staining was used to examine the integrity of elastic fibers and medial structures. Alcian blue staining was used to assess the content of acidic mucopolysaccharides and proteoglycans within the aortic wall. Images were acquired using a Leica DM6B microscope equipped with a 20× or 40× HC PLAN objective and Leica Application Suite software (version 4.10).

[0030] 5 Data Processing Data processing was performed using SPSS 13.0 software. Statistical results are expressed as mean ± standard error (±SEM). Differences between two groups were analyzed using t-tests. When comparing multiple groups, ANOVA was used, and Bonferroni test was employed for further analysis and validation. p < 0.05 was considered statistically significant. * indicates p < 0.05, ** indicates p < 0.01, and *** indicates p < 0.001.

[0031] 6 Experimental Results like Figure 2 and Figure 3 As shown, Codonopsis pilosula polysaccharide can reduce the mortality rate of aortic dissection in mice. On day 23, the mortality rate in the BAPN group was as high as 59%, and the morbidity rate was 41%, while the mortality rate in the Codonopsis pilosula polysaccharide intervention group was 25%, the morbidity rate was 50%, and the healthy rate was 25%. This indicates that Codonopsis pilosula polysaccharide can effectively reduce the mortality rate of aortic dissection in mice, and that it has a significant preventive and therapeutic effect on aortic dissection and aortic dilatation.

[0032] like Figure 4 As shown, compared to the control group mice, the BAPN group mice developed severe aortic dilatation and dissection, indicating that the model was successfully established. The Codonopsis pilosula polysaccharide intervention group developed aortic dilatation, but with milder symptoms.

[0033] like Figure 5 As shown, compared to the control group, the aortic diameter of mice in the BAPN group was significantly increased, indicating that the model was successfully established. Compared to the BAPN group, the aortic diameter of mice in the Codonopsis pilosula polysaccharide intervention group was significantly decreased. This indicates that Codonopsis pilosula polysaccharide can effectively treat aortic dilatation and aortic dissection in mice.

[0034] like Figure 6 As shown, intervention with Codonopsis pilosula polysaccharide reduced aortic dilation and dissection formation, decreased elastic fiber rupture in the aortic neutral lamina, reduced collagen deposition, and decreased glycosaminoglycan accumulation in mice. This indicates that Codonopsis pilosula polysaccharide can effectively treat aortic dilation and aortic dissection.

[0035] like Figure 7 As shown, compared to the control group, the BAPN group mice exhibited significantly increased collagen content, elastic fiber breakage count, and glycosaminoglycan content in the aortic neutral lamina, indicating successful establishment of the animal model. Conversely, compared to the BAPN group, the Codonopsis pilosula polysaccharide intervention group mice showed significantly decreased collagen content, elastic fiber breakage count, and glycosaminoglycan content in the aortic neutral lamina. This suggests that Codonopsis pilosula polysaccharide can effectively prevent and treat aortic dilation.

[0036] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. Application of Codonopsis pilosula polysaccharide in the preparation of products for the prevention and / or treatment of aortic dilatation.

2. The application according to claim 1, characterized in that, The application includes at least one of the following: (1) Application in the preparation of products that improve survival rate under aortic dilation; (2) Application in the preparation of products that inhibit aortic dilation and / or aortic dissection formation; (3) Application in the preparation of products that reduce collagen deposition in the neutral membrane of the aorta; (4) Application in the preparation of products that reduce the accumulation of glycosaminoglycans in the neutral membrane of the aorta; (5) Application in the preparation of products that reduce the diameter of the aorta.

3. The application according to claim 2, characterized in that, The application in the preparation of products that inhibit aortic dilation and / or aortic dissection includes: (2-1) Application in the preparation of products that reduce the diameter of the aorta; (2-2) Application in the preparation of products that reduce the degree of aortic arch dilation.

4. The application according to claim 1, characterized in that, The aortic dilation was β-aminopropionitrile-induced aortic dilation.

5. The application according to claim 1, characterized in that, The product in question is a medicine.

6. The application according to claim 5, characterized in that, The only active ingredient in the drug is Codonopsis pilosula polysaccharide.

7. The application according to claim 5, characterized in that, The product also includes excipients that are permitted to be added to the drug.

8. The application according to claim 7, characterized in that, The excipients include isotonic agents, buffer solutions, flavoring agents, excipients, fillers, binders, disintegrants, or lubricants.

9. The application according to claim 5, characterized in that, The routes of administration of the drug include intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, or nebulization.

10. The application according to claim 1, characterized in that, The daily dosage of the Codonopsis pilosula polysaccharide is 8-25 mg / kg.

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