Use of inulin in the preparation of a product for inhibiting cardiac fibrosis and improving cardiac function

Abstract

The application discloses application of inulin in preparation of products for inhibiting cardiac fibrosis and improving heart function. The application sets 5xFAD aging transgenic mice as an experimental model, and sets different gradient doses of inulin for dietary intervention. The results show that the inulin has a nonlinear effect on the heart protection of the aging mice, and can significantly improve the systolic and diastolic functions of the heart, reduce the abnormal deposition of myocardial interstitial collagen, down-regulate the expression of Collagen I, Collagen III and TGF-beta 1 fibrosis markers, and effectively block the aging-related cardiac fibrosis process. The inulin has natural low toxicity, wide sources and good tolerance, and can be used for preparing medicines and health foods for preventing or assisting in treating aging-related heart function decline and cardiac fibrosis, and has good clinical transformation and industrial application prospects.

Description

Technical Field

[0001] This invention belongs to the fields of bioactive application of natural dietary fiber and cardiovascular protection against aging, specifically involving the application of inulin in the preparation of products that inhibit cardiac fibrosis and improve cardiac function. Background Technology

[0002] Cardiac fibrosis is a core pathological change shared by aging, neurodegenerative diseases, metabolic disorders, and chronic cardiovascular diseases. Its main characteristics are excessive activation of myocardial fibroblasts, excessive deposition of type I and type III collagen, and myocardial interstitial remodeling, which in turn leads to a decline in ventricular systolic and diastolic function and is an important pathological basis for inducing heart failure in the elderly.

[0003] Existing research indicates that natural prebiotic inulin possesses multiple physiological activities, including regulating gut microbiota, anti-inflammation, anti-oxidation, and regulating lipid and energy metabolism. Animal experiments have confirmed that inulin has demonstrated potential cardioprotective effects in models of metabolic syndrome, type 2 diabetes, high-fat diets, and chronic kidney disease by reducing myocardial inflammation, lowering oxidative stress levels, alleviating ventricular pathological remodeling, and improving cardiac systolic and diastolic function.

[0004] However, existing publicly available studies all use disease models such as ordinary rats and conventional mice, and have not yet conducted a specific intervention evaluation on the effects of inulin on cardiac function impairment and cardiac fibrosis in aging transgenic mice. Summary of the Invention

[0005] The purpose of this invention is to provide the application of inulin in the preparation of products that inhibit cardiac fibrosis and improve cardiac function. It is demonstrated that inulin has a protective effect against cardiac function and myocardial fibrosis in 5xFAD aging transgenic mice.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides the application of inulin in the preparation of products that inhibit cardiac fibrosis and improve cardiac function.

[0007] Furthermore, the products include pharmaceuticals and health foods.

[0008] Furthermore, the application is for treating age-related decline in cardiac function and cardiac fibrosis.

[0009] Furthermore, inulin can improve cardiac systolic and diastolic function and inhibit age-related cardiac fibrosis by reducing collagen deposition in the myocardial interstitium.

[0010] Furthermore, inulin inhibits myocardial fibrosis by downregulating the gene and protein expression levels of myocardial fibrosis markers Collagen I, Collagen III, and TGF-β1.

[0011] Furthermore, the product also contains pharmaceutically acceptable excipients and / or food-acceptable excipients.

[0012] Furthermore, the dosage of inulin in the product is 5%~20% w / w.

[0013] Secondly, the present invention provides a product for preventing or treating cardiac fibrosis and improving cardiac function, wherein inulin is the active ingredient.

[0014] Furthermore, the dosage of inulin in the product is 5%~20% w / w.

[0015] The beneficial effects of this invention are as follows: (1) This invention confirms that inulin has a non-linear intervention characteristic in improving cardiac function in 5xFAD aged mice. The medium dose (10% w / w) has the best intervention effect, which can significantly increase the left ventricular ejection fraction and short axis shortening rate, and significantly improve the decline in cardiac systolic and diastolic function caused by aging.

[0016] (2) Inulin can significantly reduce collagen deposition in the myocardial interstitium and alleviate myocardial pathological remodeling. The effect is most prominent at medium doses and can effectively inhibit the process of age-related cardiac fibrosis.

[0017] (3) Inulin can downregulate the gene and protein expression of myocardial fibrosis markers Collagen I, Collagen III and TGF-β1, inhibit excessive collagen synthesis and block the pathological progression of fibrosis.

[0018] (4) Inulin is natural, safe, widely available, and well tolerated orally, making it suitable for developing intervention products for age-related myocardial damage and decreased cardiac function in middle-aged and elderly people. Attached Figure Description

[0019] Figure 1 The effects of different doses of inulin on the histopathology of cardiac tissue in 5xFAD mice; (A) shows the HE staining results, and (B) shows the Masson staining results; scale bar: 20 μm. Detailed Implementation

[0020] To better understand the technical solution of the present invention, the following detailed description is provided in conjunction with specific embodiments, but this does not limit the scope of protection of the present invention.

[0021] The inulin used in the following examples was purchased from Yuanye Biotechnology Co., Ltd., and the basic feed was synthesized by Xiehe Pharmaceutical Biotechnology Co., Ltd. The basic feed was AIN93M.

[0022] Example 1: Effects of inulin on cardiac function in 5xFAD mice SPF-grade 5xFAD transgenic mice with C57BL / 6 background, aged 6-8 weeks and weighing 18-22 g, were purchased from Cyagen Biosciences Inc. (License No.: SCXK(Ji)2021-003), and wild-type mice with the same background were selected. The breeding environment is maintained at a temperature of 22-24 °C, humidity of 50%±10%, 12 h light-dark cycle, free access to food and water, and daily feed intake is about 3.5-4 g per mouse. Inulin was uniformly mixed into AIN-93M basal diet by mass percentage.

[0023] The mice were randomly divided into 5 groups with 10-12 mice in each group. The specific grouping is as follows: Group 1: Wild control group (Control), wild-type mice were fed with standard AIN-93M basal diet; Group 2: 5xFAD model group, 5xFAD transgenic mice were fed with standard AIN-93M basal diet; Group 3: Low-dose inulin group, 5xFAD transgenic mice were fed with standard AIN-93M basal diet supplemented with 5% (w / w) inulin; Group 4: Medium-dose inulin group, 5xFAD transgenic mice were fed with standard AIN-93M basal diet supplemented with 10% (w / w) inulin; Group 5: High-dose inulin group, 5xFAD transgenic mice were fed with standard AIN-93M basal diet supplemented with 20% (w / w) inulin.

[0024] After one week of adaptive feeding, all mice received continuous dietary intervention for 8 weeks. During the intervention, the mice had normal access to food and water, and their general physiological status was routinely monitored.

[0025] After the intervention, cardiac function indicators were detected by small animal echocardiography. The results showed that compared with the wild control group, the left ventricular ejection fraction (EF) and fractional shortening (FS) of the 5xFAD model group were significantly decreased, while the left ventricular end-diastolic internal diameter (LVIDd) and left ventricular end-systolic internal diameter (LVIDs) were significantly increased, indicating significant cardiac function injury. Compared with the model group, the medium-dose inulin group (10%) had the most significant improvement in cardiac function indicators: EF and FS increased significantly, and the pathological dilation of the ventricular cavity was significantly reduced. The low-dose inulin group (5%) only showed a mild improvement trend with no statistical difference, while the improvement effect of the high-dose inulin group (20%) was weaker than that of the medium-dose group. These results suggest that the protective effect of inulin on cardiac function in 5xFAD aging mice presents an inverted U-shaped dose-effect relationship, and the medium-dose intervention has the optimal effect (Table 1).

[0026] Table 1 Cardiac function indicators detected by echocardiography in different groups

[0027] Example 2 Effect of inulin on pathological changes of myocardial fibrosis After the intervention, left ventricular myocardial tissue was taken from mice, and after paraffin sectioning, Masson staining and Sirius red staining were performed to observe and quantify the level of collagen deposition in the myocardial interstitium.

[0028] The results showed that in the 5xFAD model group, myocardial fibers were disordered, interstitial collagen was deposited in large quantities, and the degree of fibrosis was significantly increased (see [link to study]). Figure 1 After intervention with 5%, 10%, and 20% inulin, the pathological damage and degree of fibrosis in myocardial tissue were all improved, with the 10% inulin group showing the most significant improvement. The medium-dose inulin group showed a significant reduction in myocardial collagen deposition, marked recovery of myocardial tissue structure, and a significant decrease in fibrosis area. The low-dose inulin group showed limited improvement, while the high-dose inulin group had a weaker anti-fibrotic effect than the medium-dose group, further confirming that medium-dose inulin can effectively inhibit age-related myocardial fibrosis (Table 2).

[0029] Table 2. Pathological findings of myocardial fibrosis in different groups

[0030] Further qPCR and Western blot analysis were used to detect the mRNA and protein expression of Collagen I (Col1a1), Collagen III (Col3a1), and TGF-β1 in myocardial tissue. Results showed that the expression of fibrosis-related genes and proteins was significantly upregulated in the 5xFAD model group; medium-dose inulin intervention significantly inhibited the expression of the above fibrosis markers, with the most prominent effect; the low-dose group showed limited inhibition, while the high-dose group showed weaker inhibitory effects than the medium-dose group. These results suggest that inulin mainly exerts its anti-cardiac fibrosis effect by inhibiting collagen synthesis and TGF-β1 pathway activation, and that the medium dose is the optimal intervention dose under this model (Table 3).

[0031] Table 3. mRNA and protein expression of Collagen I (Col1a1), Collagen III (Col3a1), and TGF-β1 in myocardial tissue of different groups.

[0032] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made within the scope of the claims of the present invention should be included in the scope of the present invention.

Claims

1. Application of inulin in the preparation of products that inhibit cardiac fibrosis and improve cardiac function.

2. The application according to claim 1, characterized in that: The products include pharmaceuticals and health foods.

3. The application according to claim 1, characterized in that: The application is for the treatment of age-related decline in cardiac function and cardiac fibrosis.

4. The application according to claim 1, characterized in that: Inulin can improve cardiac systolic and diastolic function and inhibit age-related cardiac fibrosis by reducing collagen deposition in the myocardial interstitium.

5. The application according to claim 1, characterized in that: Inulin inhibits myocardial fibrosis by downregulating the gene and protein expression levels of myocardial fibrosis markers Collagen I, Collagen III, and TGF-β1.

6. The application according to claim 1, characterized in that: The product also contains pharmaceutically acceptable excipients and / or food-acceptable excipients.

7. The application according to claim 1, characterized in that: The dosage of inulin in the product is 5%~20% w / w.

8. A product for preventing or treating cardiac fibrosis and improving cardiac function, characterized in that: Inulin is the active ingredient.

9. The product according to claim 8, characterized in that: The dosage of inulin in the product is 5%~20% w / w.

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