Application of N1, N10-dicaffeoyl spermidine in preparation of medicine for preventing and treating atherosclerosis

Abstract

The invention discloses an application of N1, N10-dicaffeoyl spermidine in preparation of a medicine for preventing and treating atherosclerosis. Belongs to the technical field of biological medicine. When the N1, N10-dicaffeoyl spermidine is administered to an experimental animal within the dosage range of 10-25 mg / kg, the area of ApoE- / -mouse atherosclerotic plaque induced by high homocysteine (HCY) can be remarkably reduced, meanwhile, the HCY level, the levels of four blood lipid items (TG, TC, LDL-C and HDL-C) and the levels of inflammatory factors such as IL-6, IL-1beta, TNF-alpha, MCP-1 and CRP in serum of the atherosclerotic mouse can be remarkably callback, and the N1, N10-dicaffeoyl spermidine can be used for treating atherosclerotic mice. All the results prove that the N1, N10-dicaffeoyl spermidine has the effect of improving the atherosclerosis and can be used for preventing and treating cardiovascular system diseases such as the atherosclerosis.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and more specifically relates to the application of N1,N10-dicaffeoyl spermidine in the preparation of drugs for preventing and treating atherosclerosis. Background Art

[0002] Atherosclerosis is a systemic and chronic progressive vascular disease, characterized by lipid deposition, inflammatory response, and vascular remodeling. Its pathological process begins with endothelial dysfunction, accompanied by the accumulation of oxidized low-density lipoproteins under the intima, triggering monocyte infiltration and differentiation into macrophages, which then phagocytose lipids to form foam cells. At the same time, the proliferation and migration of vascular smooth muscle cells promote the formation of the fibrous cap, ultimately leading to arterial wall sclerosis, lumen stenosis, and even occlusion. This lesion can affect the entire vascular bed, causing ischemic damage to multiple organs such as the heart, brain, and kidneys, and is the main pathological basis of coronary heart disease, stroke, and peripheral arterial disease. Due to its high incidence, high disability rate, and high mortality rate, atherosclerosis has become a major global health challenge, imposing a heavy burden on medical resources and social economy. Currently, in-depth study of its molecular mechanism and development of precise prevention and treatment strategies are important research directions in the cardiovascular field.

[0003] The current clinical drug treatment for atherosclerosis mainly adopts three major intervention strategies: lipid-lowering regulation, antiplatelet aggregation, and anti-inflammatory and plaque stabilization. However, traditional chemically synthesized drugs generally have obvious adverse reactions, are prone to drug resistance and drug dependence, and other clinical limitations during long-term use. It is worth noting that a series of breakthroughs have been made in the research of natural drugs in recent years. A large amount of experimental evidence shows that a variety of active ingredients of traditional Chinese medicines, such as curcumin, colchicine, and cryptotanshinone, can effectively regulate abnormal lipid metabolism, inhibit the inflammatory response network, and repair damaged endothelial function through multi-target and multi-pathway synergistic effects, thereby achieving a comprehensive intervention in the process of atherosclerosis. These important findings not only provide innovative ideas for the prevention and treatment of cardiovascular diseases, but also lead to the in-depth development and research of natural drug active ingredients. Compared with traditional chemical drugs, natural active ingredients have unique application value and development prospects in the prevention and treatment of cardiovascular diseases due to their multi-target synergistic regulation characteristics, good biological safety, and low toxicity and side effects.

[0004] Currently, there are few reports on the biological activities of N1,N10-dicaffeoyl spermidine, and no relevant research on the use of N1,N10-dicaffeoyl spermidine for the prevention and treatment of atherosclerosis has been reported. Summary of the Invention

[0005] Application in atherosclerotic drugs. Through preliminary animal experiments, the present invention found that N1,N10-dicaffeoylspermidine has a significant effect in alleviating atherosclerosis. Further, developing it into a drug that can be used for the prevention and treatment of atherosclerosis will have great clinical application value.

[0006] N1,N10-dicaffeoylspermidine, the full English name is (E)-3-(3,4-dihydroxyphenyl)-N-(3-((4-((E)-3-(3,4-dihydroxyphenyl)acrylamido)butyl)amino)propyl)acrylamide, abbreviated as N1,N3-bis(caffeoyl)spermidine or N1,N3-di-caffeoylspermidine, and its molecular formula is C 25 H 31 N3O6, with a molecular weight of 469.22, and its chemical structural formula is shown in Formula (1):

[0007] Formula (1) In order to achieve the above object, the present invention adopts the following technical solutions: Application of N1,N10-dicaffeoylspermidine in the preparation of drugs for the prevention and treatment of atherosclerosis.

[0008] Furthermore, it can reduce the plaque area in the aorta of atherosclerotic mice.

[0009] Furthermore, it can reduce the level of homocysteine (HCY) in the serum.

[0010] Furthermore, it can adjust back the levels of the four lipid parameters in the serum, including TG, TC, LDL-C, and HDL-C.

[0011] Furthermore, it can adjust back the levels of inflammatory factors such as IL-6, IL-1β, TNF-α, MCP-1, and CRP in the serum.

[0012] A drug for the prevention and treatment of atherosclerosis, characterized in that it includes N1,N10-dicaffeoylspermidine.

[0013] Furthermore, the dosage form is an orally administrable dosage form, an external patch, or an injection dosage form permitted in pharmacy.

[0014] Furthermore, the single application dose of N1,N10-dicaffeoylspermidine is 10 - 25 mg / kg.

[0015] As can be seen from the above technical solutions, compared with the prior art, the beneficial effects achieved by the present invention are as follows: within the dose range of 10-25 mg / kg administered to experimental animals, N1,N10-dicaffeoyl spermidine can significantly reduce the atherosclerotic plaque area in ApoE- / - mice induced by HCY, and at the same time can significantly reverse the HCY level, the levels of the four lipid items (TG, TC, LDL-C, HDL-C), and the levels of inflammatory factors such as IL-6, IL-1β, TNF-α, MCP-1, and CRP in the serum of atherosclerotic mice. The above all confirm that N1,N10-dicaffeoyl spermidine has the effect of improving atherosclerosis and can be used for the prevention and treatment of cardiovascular system diseases such as atherosclerosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained according to the provided drawings.

[0017] Figure 1 Effect of N1,N10-dicaffeoyl spermidine on plaque area in the aorta of mice in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p<0.001; compared with the model group, *** p<0.001).

[0018] Figure 2 Effect of N1,N10-dicaffeoyl spermidine on Hcy level in the serum of mice in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p<0.001; compared with the model group, ** p<0.01, *** p<0.001).

[0019] Figure 3Effect of N1,N10-dicaffeoyl spermidine on TG level in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p < 0.001; compared with the model group, *** p < 0.001).

[0020] Figure 4 Effect of N1,N10-dicaffeoyl spermidine on TC level in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, # p < 0.05; compared with the model group, ** p < 0.01).

[0021] Figure 5 Effect of N1,N10-dicaffeoyl spermidine on LDL-C level in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p < 0.001; compared with the model group, ** p < 0.01, *** p < 0.001).

[0022] Figure 6 Effect of N1,N10-dicaffeoyl spermidine on HDL-C level in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ## p < 0.01; compared with the model group, ns > 0.05, * p < 0.05, ** p < 0.01, *** p < 0.001).

[0023] Figure 7Effect of N1,N10-dicaffeoyl spermidine on the level of inflammatory factor IL-6 in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p < 0.001; compared with the model group, ** p < 0.01, *** p < 0.001).

[0024] Figure 8 Effect of N1,N10-dicaffeoyl spermidine on the level of inflammatory factor IL-1β in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p < 0.001; compared with the model group, *** p < 0.001).

[0025] Figure 9 Effect of N1,N10-dicaffeoyl spermidine on the level of inflammatory factor TNF-α in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p < 0.001; compared with the model group, *** p < 0.001).

[0026] Figure 10 Effect of N1,N10-dicaffeoyl spermidine on the level of inflammatory factor MCP-1 in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoyl spermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoyl spermidine; compared with the normal group, ### p < 0.001; compared with the model group, ** p < 0.01, *** p < 0.001).

[0027] Figure 11Effect of N1,N10-dicaffeoylspermidine on the level of inflammatory factor CRP in mouse serum in Experiment 1 of the present invention (C is the normal group, M is the model group, Y is the positive drug atorvastatin group, NNDCP-H is the high-dose group of N1,N10-dicaffeoylspermidine, NNDCP-L is the low-dose group of N1,N10-dicaffeoylspermidine; compared with the normal group, ### p < 0.001; compared with the model group, * p < 0.05, *** p < 0.001). Specific embodiments

[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0029] The N1,N10-dicaffeoylspermidine used in the following examples is the compound shown in the above formula (1), and can be obtained by commercial purchase or experimental self-preparation.

[0030] The medicaments required for the present invention are conventional experimental medicaments, purchased from commercial channels; the experimental methods not mentioned are conventional experimental methods, which will not be elaborated one by one here. Example 1

[0031] A drug for preventing and treating atherosclerosis, in an oral dosage form, comprising N1,N10-dicaffeoylspermidine, wherein the single application dose of N1,N10-dicaffeoylspermidine is 10 mg / kg. Example 2

[0032] A drug for preventing and treating atherosclerosis, in an oral dosage form, comprising N1,N10-dicaffeoylspermidine, wherein the single application dose of N1,N10-dicaffeoylspermidine is 25 mg / kg. Example 3

[0033] A drug for preventing and treating atherosclerosis, in an injection dosage form, comprising N1,N10-dicaffeoylspermidine, wherein the single application dose of N1,N10-dicaffeoylspermidine is 10 mg / kg. Example 4

[0034] A drug for preventing and treating atherosclerosis, in an external patch dosage form, comprising N1,N10-dicaffeoylspermidine, wherein the single application dose of N1,N10-dicaffeoylspermidine is 25 mg / kg.

[0035] Experiment 1 The following animal experiments further illustrate the effects of the above Examples 1 to 4: I. Animal experiment design An atherosclerotic model of ApoE- / - mice was induced by HCY. After intragastric administration of N1,N10-dicaffeoyl spermidine, the preventive and therapeutic effects of N1,N10-dicaffeoyl spermidine on atherosclerotic mice were evaluated by the plaque area of the mouse aorta, serum HCY level, four lipid parameters (TG, TC, LDL-C, HDL-C) levels, and inflammatory factor (IL-6, IL-1β, TNF-α, MCP-1, CRP) levels.

[0036] II. Experimental procedure 1. Experimental animals Healthy SPF-grade male ApoE- / - mice (6 - 8 w) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Laboratory animal license number: SCXK (Jing) 2021 - 0006). They were adaptively fed in an SPF-grade standard laboratory, and the feeding conditions for each group of animals were the same: environmental temperature (25°C), relative humidity (50% - 60%). They had free access to food and water.

[0037] 2. Experimental method ApoE- / - mice were adaptively fed for 3 days before undergoing the modeling. One day before the modeling, they were randomly divided into a normal group, a model group, a positive drug group (atorvastatin), and an N1,N10-dicaffeoyl spermidine group (low-dose group 10 mg / kg, high-dose group 25 mg / kg), a total of 5 groups, with 8 mice in each group. After adaptive feeding, the modeling was continuously carried out for 8 weeks. The normal group was fed with ordinary feed, and the other groups were fed with a special feed containing 1.7% high-methionine. Administration started in the 9th week. The normal group and the model group were given normal saline (0.1 mL / 10g / d), the positive drug group was given atorvastatin (10 mg / kg / d), and the administration doses of the low-dose and high-dose groups of N1,N10-dicaffeoyl spermidine were 10 mg / kg / d and 25 mg / kg / d, respectively. Each group of mice was intragastrically administered the drugs in sequence from 8:00 to 12:00 every morning for 10 consecutive weeks.

[0038] 3. Aortic plaque area After 10 weeks of drug administration, the mice were fasted and water-deprived for 12 h. After taking blood by eye socket puncture, they were sacrificed by cervical dislocation. The whole aorta was removed after perfusion. Subsequently, gross oil red O staining was performed, and the red areas were the plaques.

[0039] 4. Determination of HCY level Centrifuge the blood sample at 3000 r for 10 min at 4°C. After taking the supernatant, centrifuge it at 10000 r for 5 min, collect the supernatant, and detect the level of HCY in the serum by ELISA method.

[0040] 5. Determination of the levels of four lipid items Centrifuge the blood sample at 3000 r for 10 min at 4°C. After taking the supernatant, centrifuge it at 10000 r for 5 min, collect the supernatant, and detect the levels of TG, TC, LDL-C, and HDL-C in the serum by ELISA method.

[0041] 6. Determination of the levels of inflammatory factors Centrifuge the blood sample at 3000 r for 10 min at 4°C. After taking the supernatant, centrifuge it at 10000 r for 5 min, collect the supernatant, and detect the levels of IL-6, IL-1β, TNF-α, MCP-1, and CRP in the serum by ELISA method.

[0042] 7. Data processing For the data processing of this invention, ImageJ and Graphpad Prism 9.5 are used for data analysis and statistics. The obtained results are all expressed as mean ± standard deviation (X±S). One-way ANOVA is used for data processing of the inter-group difference comparison. The difference is considered statistically significant with p<0.05 as the standard.

[0043] III. Experimental results 1. Effect on the aortic plaque area of mice The results of the effect of N1,N10-dicaffeoyl spermidine on the aortic plaque area of mice are shown in Figure 1 shown below.

[0044] Compared with the normal control group (7.32±0.17%), the aortic plaque area of the model group mice (18.03±0.78%) increased significantly (p<0.001), indicating that the HCY-induced atherosclerotic mouse model was successful. Compared with the model group, the aortic plaque area of the positive drug group mice (8.93±1.39%) decreased significantly (p<0.001). The aortic plaque area of each dose group of N1,N10-dicaffeoyl spermidine decreased significantly (p<0.001), showing a certain positive dose correlation, that is, the larger the administration dose, the smaller the plaque area.

[0045] In summary, atherosclerosis significantly increased the aortic plaque area. Each dose group of N1,N10-dicaffeoyl spermidine could reduce the aortic plaque area of mice to varying degrees.

[0046] 2. Effect on the level of HCY in the serum of mice The results of the effect of N1,N10-dicaffeoylspermidine on the HCY level in the serum of mice are shown in Figure 2 as follows.

[0047] Compared with the normal control group (7.30 ± 1.34 μmol / L), the content of HCY (28.27 ± 5.03 μmol / L) in the serum of model mice increased significantly (p < 0.001), indicating that the content of HCY in the serum of atherosclerotic mice induced by HCY increased. Compared with the model group, the content of HCY (14.59 ± 0.53 μmol / L) in the serum of the positive drug group mice decreased significantly (p < 0.001), and the content of HCY in the serum of mice in each dose group of N1,N10-dicaffeoylspermidine decreased significantly (p < 0.01).

[0048] In summary, the content of HCY in the serum of atherosclerotic mice induced by HCY increased significantly, and each dose group of N1,N10-dicaffeoylspermidine could reduce the content of HCY in the serum of mice to varying degrees.

[0049] 3. Effect on the levels of four serum lipids in mice The results of the effect of N1,N10-dicaffeoylspermidine on the levels of four serum lipids (TG, TC, LDL-C, HDL-C) in mice are shown in Figure 3 , 4 , 5, and 6. Compared with the normal control group (8.40 ± 0.95 mmol / L), the content of TG (17.62 ± 3.17 mmol / L) in the serum of model group mice increased significantly (p < 0.001), indicating that the content of TG in the serum of atherosclerotic mice induced by HCY increased. Compared with the model group, the content of TG (11.35 ± 1.35 mmol / L) in the serum of the positive drug group mice decreased significantly (p < 0.001), and the content of TG in the serum of mice in each dose group of N1,N10-dicaffeoylspermidine decreased significantly (p < 0.001).

[0050] Compared with the normal control group (1.26 ± 0.14 mmol / L), the content of TC (1.69 ± 0.17 mmol / L) in the serum of model group mice increased significantly (p < 0.05), indicating that the content of TC in the serum of atherosclerotic mice induced by HCY increased. Compared with the model group, the content of TC (1.14 ± 0.21 mmol / L) in the serum of the positive drug group mice decreased significantly (p < 0.01), and the content of TC in the serum of mice in each dose group of N1,N10-dicaffeoylspermidine decreased significantly (p < 0.01).

[0051] Compared with the normal control group (9.33 ± 2.10 mmol / L), the content of LDL-C (16.95 ± 3.20 mmol / L) in the serum of mice in the model group was significantly increased (p < 0.001), indicating that the content of LDL-C in the serum of HCY-induced atherosclerotic mice was increased. Compared with the model group, the content of LDL-C (10.97 ± 0.84 mmol / L) in the serum of mice in the positive drug group was significantly decreased (p < 0.001), and the content of LDL-C in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine was significantly decreased (p < 0.01).

[0052] Compared with the normal control group (1.87 ± 0.08 mmol / L), the content of HDL-C (1.44 ± 0.11 mmol / L) in the serum of mice in the model group was significantly decreased (p < 0.01), indicating that the content of HDL-C in the serum of HCY-induced atherosclerotic mice was decreased. Compared with the model group, the content of HDL-C (2.10 ± 0.07 mmol / L) in the serum of mice in the positive drug group was significantly increased (p < 0.001), and the content of HDL-C in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine was significantly increased (p < 0.05).

[0053] In summary, the contents of TG, TC, and LDL-C in the serum of the HCY-induced atherosclerotic mouse model were significantly increased, and each dose group of N1,N10-dicaffeoyl spermidine could reduce the contents of TG, TC, and LDL-C in the serum of mice to varying degrees. The content of HDL-C in the serum of the HCY-induced atherosclerotic mouse model was significantly decreased, and each dose group of N1,N10-dicaffeoyl spermidine could increase the content of HDL-C in the serum of mice to varying degrees.

[0054] 4. Effects on the levels of inflammatory factors in the serum of mice The results of the effects of N1,N10-dicaffeoyl spermidine on the levels of inflammatory factors (IL-6, IL-1β, TNF-α, MCP-1, CRP) in the serum of mice are shown in Figure 7 、 8 、9, 10, 11.

[0055] Compared with the normal control group (28.67 ± 6.31 pg / mL), the content of IL-6 (100.22 ± 5.12 pg / mL) in the serum of mice in the model group was significantly increased (p < 0.001), indicating that the content of IL-6 in the serum of HCY-induced atherosclerotic mice was increased. Compared with the model group, the content of IL-6 (48.67 ± 20.18 pg / mL) in the serum of mice in the positive drug group was significantly decreased (p < 0.001), and the content of IL-6 in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine was significantly decreased (p < 0.01).

[0056] Compared with the normal control group (34.55 ± 1.62 pg / mL), the content of IL-1β in the serum of mice in the model group (65.26 ± 6.09 pg / mL) increased significantly (p < 0.001), indicating an increase in the content of IL-1β in the serum of atherosclerotic mice induced by HCY. Compared with the model group, the content of IL-1β in the serum of mice in the positive drug group (40.09 ± 4.22 pg / mL) decreased significantly (p < 0.001), and the content of IL-1β in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine decreased significantly (p < 0.001).

[0057] Compared with the normal control group (40.06 ± 3.53 pg / mL), the content of TNF-α in the serum of mice in the model group (105.90 ± 4.50 pg / mL) increased significantly (p < 0.001), indicating an increase in the content of TNF-α in the serum of atherosclerotic mice induced by HCY. Compared with the model group, the content of TNF-α in the serum of mice in the positive drug group (50.90 ± 5.62 pg / mL) decreased significantly (p < 0.001), and the content of TNF-α in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine decreased significantly (p < 0.001).

[0058] Compared with the normal control group (75.87 ± 3.43 pg / mL), the content of MCP-1 in the serum of mice in the model group (113.45 ± 16.16 pg / mL) increased significantly (p < 0.001), indicating an increase in the content of MCP-1 in the serum of atherosclerotic mice induced by HCY. Compared with the model group, the content of MCP-1 in the serum of mice in the positive drug group (89.55 ± 8.22 pg / mL) decreased significantly (p < 0.01), and the content of MCP-1 in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine decreased significantly (p < 0.001).

[0059] Compared with the normal control group (1.56 ± 0.18 ng / mL), the content of CRP in the serum of mice in the model group (2.83 ± 0.75 ng / mL) increased significantly (p < 0.001), indicating an increase in the content of CRP in the serum of atherosclerotic mice induced by HCY. Compared with the model group, the content of CRP in the serum of mice in the positive drug group (1.56 ± 0.21 ng / mL) decreased significantly (p < 0.001), and the content of CRP in the serum of mice in each dose group of N1,N10-dicaffeoyl spermidine decreased significantly (p < 0.05).

[0060] In summary, the contents of IL-6, IL-1β, TNF-α, MCP-1, and CRP in the serum of the atherosclerotic mouse model induced by HCY were significantly increased, and each dose group of N1,N10-dicaffeoyl spermidine could reduce the contents of IL-6, IL-1β, TNF-α, MCP-1, and CRP in the serum of mice to varying degrees.

[0061] During the whole process of animal administration, no mice died, and there were no abnormal conditions in the appearance and behavior of the mice.

[0062] In this specification, each embodiment is described in a progressive manner. The key point of each embodiment is to illustrate the differences from other embodiments. For the same or similar parts among the embodiments, reference can be made to each other.

[0063] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but will be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Application of N1, N10-dicaffeoylspermidine in the preparation of drugs for the prevention and treatment of atherosclerosis.

2. The use according to claim 1, characterized in that It can reduce the plaque area in the aorta of atherosclerotic mice.

3. The use according to claim 1, characterized in that It can significantly reduce serum homocysteine ​​levels.

4. The use according to claim 1, characterized in that It can adjust the levels of four blood lipids in serum, including TG, TC, LDL-C, and HDL-C.

5. The use according to claim 1, characterized in that It can adjust the levels of inflammatory factors such as IL-6, IL-1β, TNF-α, MCP-1, and CRP in serum.

6. A drug for preventing and treating atherosclerosis, characterized in that: Including N1,N10-dicaffeoylspermidine.

7. The drug according to claim 6, characterized in that The dosage form is a pharmaceutically acceptable oral dosage form, external patch or injection dosage form.

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