Application of N1-dihydrocaffeoyl-N10-caffeoyl spermidine in preparation of medicine for preventing and treating Alzheimer disease
By using N1-dihydrocaffeyl-N10-cafeamentoylspermidine as an active compound, drugs to prevent and treat Alzheimer's disease were developed, and the problem that existing AD treatment drugs cannot effectively reverse or delay disease progression was solved, and the effect of significantly improving the memory capacity of AD mice and reducing brain tissue inflammation and Aβ levels was achieved.
Patent Information
- Application Number
- CN202510558296.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-29
- Publication Date
- 2025-06-27
AI Technical Summary
Existing Alzheimer's disease (AD) treatment drugs cannot effectively reverse or delay disease progression, and have side effects, lacking multi-target, efficient and low-toxic treatment strategies.
Using N1-dihydrocaprolactyl-N10-cafeamentylspermidine as an active compound, the structure of the caffeic acid group and the spermine skeleton was developed to prevent and treat AD.
It significantly improves the working memory, spatial memory and learning ability of AD mice, reduces the level of inflammatory factors in brain tissue, increases the antioxidant SOD and GSH content, and reduces the levels of Aβ40 and Aβ42, demonstrating its effectiveness in preventing and treating AD.
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Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of biomedicine, and more specifically relates to the application of N1-dihydrocaffeoyl-N10-caffeoyl spermidine in the preparation of drugs for preventing and treating Alzheimer's disease. Background Art
[0002] Alzheimer's disease (AD) is a neurodegenerative disease mainly characterized by progressive cognitive impairment and memory decline, accounting for 60%-70% of global dementia cases. According to statistics from the World Health Organization (WHO), there are approximately 55 million AD patients globally, and it is expected to increase to 139 million by 2050. AD not only seriously impairs the quality of life of patients, but also brings a huge economic burden to families and society. It is estimated that the global medical and nursing costs related to AD exceeded $1 trillion in 2020, and there is currently no effective cure, urgently requiring the development of new prevention and treatment drugs.
[0003] Currently, the clinical treatment drugs for AD mainly include cholinesterase inhibitors (such as donepezil, rivastigmine) and NMDA receptor antagonists (such as memantine). Although these drugs can improve cognitive symptoms in the short term, they cannot reverse or delay the disease progression, and long-term use may cause side effects such as gastrointestinal reactions and dizziness. In recent years, monoclonal antibodies targeting β-amyloid (Aβ) (such as Aducanumab, Lecanemab) have shown certain Aβ clearance ability in clinical trials, but their efficacy is still controversial, and they may be accompanied by serious adverse reactions such as cerebral edema and microbleeding. In addition, the drug research and development targeting pathological mechanisms such as hyperphosphorylation of tau protein, neuroinflammation, and oxidative stress are still in the exploratory stage, without breakthrough progress. The limitations of existing drugs highlight the urgent need to develop new treatment strategies with multiple targets, high efficiency, and low toxicity.
[0004] Natural products and monomeric components of traditional Chinese medicine have become important sources for the development of new drugs for Alzheimer's disease (AD) due to their structural diversity, multi-target action characteristics, and high biological safety. For example, huperzine A plays a dual role by inhibiting cholinesterase and antagonizing NMDA receptors; curcumin has entered clinical trials with its anti-inflammatory, antioxidant, and Aβ aggregation inhibitory activities; and Ginkgo biloba extract exhibits neuroprotective potential by improving cerebral blood flow and mitochondrial function. Compared with synthetic drugs, natural active ingredients usually have lower toxic and side effects and can intervene in the complex pathological network of AD through multi-pathway synergy, such as simultaneously regulating Aβ metabolism, abnormal modification of tau protein, oxidative stress, and synaptic plasticity. Although some natural components have problems such as low bioavailability and poor blood-brain barrier penetration ability, their drug properties can be significantly optimized through structural modification or nano-delivery technology (such as the improvement of dicaffeoyl quinic acid derivatives). Therefore, screening for new active molecules with clear targets and mechanisms from natural products has become a frontier direction in the research and development of AD drugs.
[0005] The compound N1-dihydrocaffeoyl-N10-caffeoylspermidine of the present invention is an active compound isolated from traditional Chinese medicines such as Lycium barbarum. Its structure integrates caffeic acid groups and spermidine skeletons, and is speculated to have antioxidant, anti-inflammatory, and neuroprotective activities. Currently, there are few reports on the biological activities of N1-dihydrocaffeoyl-N10-caffeoylspermidine, and no relevant research on the use of N1-dihydrocaffeoyl-N10-caffeoylspermidine for the prevention and treatment of Alzheimer's disease has been reported. Summary of the Invention
[0006] In view of this, the present invention provides the use of N1-dihydrocaffeoyl-N10-caffeoylspermidine in the preparation of drugs for the prevention and treatment of Alzheimer's disease. Through preliminary animal experiments, the present invention found that N1-dihydrocaffeoyl-N10-caffeoylspermidine has a significant effect on improving Alzheimer's disease. Further developing it into a drug capable of preventing and treating Alzheimer's disease will have great clinical application value.
[0007] N1-dihydrocaffeoyl-N10-caffeoylspermidine, with the molecular formula C 25 H 33 N3O6, the full English name is (E)-3-(3,4-dihydroxyphenyl)-N-(3-((4-(3-(3,4-dihydroxyphenyl)propanamido)butyl)amino)propyl)acrylamide, the English abbreviation is N1-dihydrocaffeoyl-N10-caffeoylspermidine, the molecular weight is 471.24, and its chemical structural formula is shown in Formula (1): Formula (1) To achieve the above object, the present invention adopts the following technical solutions: Use of N1-dihydrocaffeoyl-N10-caffeoylspermidine in the preparation of a medicament for preventing and treating AD.
[0008] Furthermore, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the spontaneous alternation response rate of AD mice in the Y-maze test, that is, improve their working memory ability.
[0009] Furthermore, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the ability of AD mice to recognize new things, that is, improve their learning ability.
[0010] Furthermore, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly reduce the escape latency of AD mice in the Morris water maze test and increase the number of times of crossing the platform, that is, improve their spatial memory ability.
[0011] Furthermore, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly reduce the contents of inflammatory factors TNF-α, IL-1β and IL-6 in AD mice.
[0012] Furthermore, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the contents of SOD and GSH in the brain tissue of AD mice.
[0013] Furthermore, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly reduce Aβ 40 and Aβ 42 content in AD mice.
[0014] A medicament for preventing and treating Alzheimer's disease, characterized in that it comprises N1-dihydrocaffeoyl-N10-caffeoylspermidine.
[0015] Furthermore, the dosage form is an orally administrable dosage form, an external patch or an injection dosage form permitted in pharmacy.
[0016] From the above technical solutions, it can be seen that compared with the prior art, the beneficial effects obtained by the present invention are as follows: in the dose range of 10-25 mg / kg given to experimental animals, N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly improve the working memory, spatial memory and learning ability of D-galactose combined with aluminum trichloride-induced AD mice, and significantly reduce the contents of inflammatory factors TNF-α, IL-1β and IL-6 in the brain tissue of AD mice, significantly increase the levels of SOD and GSH, and at the same time significantly reduce Aβ 40 and Aβ 42Level. The above has confirmed that N1-dihydrocaffeoyl-N10-caffeoylspermidine has the effect of preventing and treating AD and can be used for the prevention and treatment of neurodegenerative diseases such as AD. Description of the Drawings
[0017] 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 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.
[0018] Figure 1 Effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the body weight of AD mice (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine; compared with the normal group, ## p <0.01; compared with the model group, * p <0.05, ** p <0.01) Figure 2 Effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the spontaneous alternation response rate of AD mice in the Y-maze experiment (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine; compared with the normal group, ## p <0.01; compared with the model group, ** p <0.01, *** p <0.001) Figure 3 Effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the ability of AD mice to distinguish new objects in the novel object recognition experiment (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine; compared with the normal group, # p <0.05; compared with the model group, ** p <0.01, *** p <0.001) Figure 4 To investigate the effects of N1-dihydrocaffeoyl-N10-caffeoyl spermidine on the escape latency and the number of platform crossings in AD mice by Morris water maze experiment (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine; compared with the model group, * p <0.05) Figure 5 To investigate the contents of inflammatory factors TNF-α, IL-1β, and IL-6 in the brain tissues of AD mice by N1-dihydrocaffeoyl-N10-caffeoyl spermidine (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine; compared with the normal group, ### p <0.001; compared with the model group, ** p <0.01, *** p <0.001) Figure 6 To investigate the effects of N1-dihydrocaffeoyl-N10-caffeoyl spermidine on the contents of oxidative stress factors SOD and GSH in the brain tissues of AD mice (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine; compared with the normal group, ### p <0.001; compared with the model group, ** p <0.01) Figure 7 To investigate the effects of N1-dihydrocaffeoyl-N10-caffeoyl spermidine on Aβ in the brain tissues of AD mice 40 and Aβ 42 contents (C is the normal group, M is the model group, P is the positive drug donepezil group, NDNCP-H is the high-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine, NDNCP-L is the low-dose group of N1-dihydrocaffeoyl-N10-caffeoyl spermidine; compared with the normal group, ## p <0.01, ### p <0.001; compared with the model group, ** p <0.01, *** p<0.001) Specific embodiments
[0019] The following will clearly and completely describe the technical solutions in the embodiments of the present invention 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 of 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.
[0020] N1-dihydrocaffeoyl-N10-caffeoylspermidine 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.
[0021] The medicaments required for the present invention are conventional experimental medicaments and are purchased from commercial channels; the experimental methods not mentioned are conventional experimental methods and will not be elaborated here one by one. Example 1
[0022] A drug for preventing and treating Alzheimer's disease, in an oral dosage form, comprising N1-dihydrocaffeoyl-N10-caffeoylspermidine, wherein the single application dose of N1-dihydrocaffeoyl-N10-caffeoylspermidine is 10 mg / kg. Example 2
[0023] A drug for preventing and treating Alzheimer's disease, in an oral dosage form, comprising N1-dihydrocaffeoyl-N10-caffeoylspermidine, wherein the single application dose of N1-dihydrocaffeoyl-N10-caffeoylspermidine is 25 mg / kg. Example 3
[0024] A drug for preventing and treating Alzheimer's disease, in an injection dosage form, comprising N1-dihydrocaffeoyl-N10-caffeoylspermidine, wherein the single application dose of N1-dihydrocaffeoyl-N10-caffeoylspermidine is 10 mg / kg. Example 4
[0025] A drug for preventing and treating Alzheimer's disease, in an external patch dosage form, comprising N1-dihydrocaffeoyl-N10-caffeoylspermidine, wherein the single application dose of N1-dihydrocaffeoyl-N10-caffeoylspermidine is 25 mg / kg.
[0026] The following animal experiments further illustrate the effects of the above Examples 1 to 4: I. Animal experiment design An Alzheimer's disease (AD) mouse model was induced by D-galactose combined with aluminum chloride (AlCl3). After intragastric administration of N1-dihydrocaffeoyl-N10-caffeoylspermidine, the preventive and therapeutic effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on Alzheimer's disease were evaluated by the body weight of mice, Y-maze test, novel object recognition test, Morris water maze test, Aβ 40 and Aβ 42 content.
[0027] II. Experimental procedure 1. Experimental animals Healthy SPF-grade ICR mice, male, weighing 20 - 30 g, were provided by the Experimental Animal Center of Ningxia Medical University (Experimental Animal Use License SYSK (Ning) 2020 - 0001), and were housed in an SPF-grade barrier environment with 12 h of light and 12 h of darkness, and free access to food and water.
[0028] 2. Experimental methods An Alzheimer's disease (AD) mouse model was induced by D-galactose combined with aluminum chloride (AlCl3). After 3 days of adaptive feeding of 48 mice, they were randomly divided into 5 groups according to their body weight: normal group (saline), model group (saline), donepezil positive drug group (5 mg / kg), N1-dihydrocaffeoyl-N10-caffeoylspermidine low-dose group (NDNCP-L, 10 mg / kg / d), N1-dihydrocaffeoyl-N10-caffeoylspermidine high-dose group (NDNCP-H, 25 mg / kg / d), with 10 mice in each group. Donepezil and N1-dihydrocaffeoyl-N10-caffeoylspermidine were both dissolved in saline and administered by intragastric gavage at a dose of 10 ml / kg. Mice were subcutaneously injected with D-galactose (200 mg / kg) at a fixed time point every day, and simultaneously intragastrically administered 150 mg / kg AlCl3 to induce an AD model (the success of the model induction was judged by behavioral experiments 5 weeks after the mice were modeled), and the normal group mice were subcutaneously injected and intragastrically administered an equal volume of saline; intragastric administration was given 4 hours later. The above modeling and intragastric administration were both once a day for 10 consecutive weeks of modeling and administration.
[0029] 3. Y-maze test After 10 weeks of drug administration in each group of mice, the Y-maze test was used to investigate the effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the working memory ability of AD mice, and the spontaneous alternation response rate of each mouse was calculated for evaluation.
[0030] 4. Novel object recognition test After 10 weeks of drug administration to each group of mice, the effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the learning and memory ability of AD mice was investigated through a novel object recognition experiment, and the evaluation was carried out by calculating the preference index of each mouse.
[0031] 5. Morris water maze experiment After 10 weeks of drug administration to each group of mice, the effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the spatial memory ability of AD mice was investigated through the Morris water maze experiment (continuously measured for 5 days), and the evaluation was carried out by the escape latency and the number of times of crossing the platform of each mouse.
[0032] 6. TNF-α, IL-1β, IL-6, SOD, GSH, Aβ 40 and Aβ 42 Content determination After 10 weeks of drug administration to each group of mice and completion of the behavioral tests, serum was collected, and then the mice were decapitated and sacrificed by cervical dislocation. The whole brain was taken by decapitation on ice, immediately frozen in liquid nitrogen, and transferred to -80 °C for storage after the experiment for standby. The mouse brain tissue was ground evenly with a tissue grinder to make a brain tissue homogenate, centrifuged at 5000 xg / min for 10 min at 4 °C, the supernatant was collected, and a kit was used to detect TNF-α, IL-1β, IL-6, SOD, GSH, Aβ 40 and Aβ 42 content.
[0033] 7. Data processing For the data processing of this invention, ImageJ and Graphpad Prism 9.5 were used for data analysis and statistics. The obtained results were all expressed as mean ± standard deviation (X±S). One-way ANOVA was used for data processing of the inter-group difference comparison, and p<0.05 was used as the standard for statistical significance of the difference.
[0034] III. Experimental results 1. Effect on mouse body weight The results of the effect of N1-dihydrocaffeoyl-N10-caffeoylspermidine on mouse body weight are shown in Figure 1 the figure.
[0035] After 10 weeks of drug administration to each group of mice, compared with the control group, the body weight of the mice in the model group was significantly reduced ( p <0.01). Compared with the model group, the body weight of the mice in the donepezil positive drug group had an upward trend, but the difference was not statistically significant; the body weight of the mice in the low-dose group of N1-dihydrocaffeoyl-N10-caffeoylspermidine was significantly increased ( p<0.01), approaching the normal group level. The above indicates that N1-dihydrocaffeoyl-N10-caffeoylspermidine has a certain ameliorating effect on the weight loss caused by modeling in mice.
[0036] 2. Effects on the spontaneous alternation response rate of mice The results of investigating the effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the spontaneous alternation response rate of AD mice by the Y-maze experiment are shown in Figure 2 as follows.
[0037] The results showed that compared with the control group, the spontaneous alternation rate of mice in the model group was significantly decreased ( p <0.01), indicating that the AD mouse model was successfully established, and D-galactose combined with AlCl3 could significantly damage the working memory ability of mice. Compared with the model group, the spontaneous alternation rates of mice in the positive drug group and the N1-dihydrocaffeoyl-N10-caffeoylspermidine group were significantly increased ( p <0.001 or p <0.01). The above suggests that both the positive drug and N1-dihydrocaffeoyl-N10-caffeoylspermidine have obvious protective effects on the damage of working memory ability in AD mice.
[0038] 3. Effects on the ability of mice to recognize novel objects The results of the effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the ability of AD mice to recognize novel objects are shown in Figure 3 as follows.
[0039] The results showed that compared with the control group, the novel object recognition index of mice in the model group was significantly decreased ( p <0.05), indicating that the AD mouse model was successfully established, and D-galactose combined with AlCl3 could significantly damage the learning and memory ability of mice. Compared with the model group, the cognition of mice in the positive drug group and the high-dose N1-dihydrocaffeoyl-N10-caffeoylspermidine group increased most significantly ( p <0.001 or p <0.05). The above suggests that both the positive drug and N1-dihydrocaffeoyl-N10-caffeoylspermidine have obvious protective effects on the damage of the ability of AD mice to distinguish novel objects.
[0040] 4. Effects on the escape latency and the number of platform crossings of mice The results of investigating the effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the escape latency and the number of platform crossings of AD mice by the Morris water maze experiment are shown in Figure 4 as follows.
[0041] The results showed that, compared with the control group, the escape latency of the mice in the model group increased, and the number of times of crossing the platform tended to decrease, but the difference was not statistically significant. Compared with the model group, the escape latency of the mice in the positive drug group decreased, and the number of times of crossing the platform increased significantly ( p <0.05), and the escape latency of the mice in the N1-dihydrocaffeoyl-N10-caffeoylspermidine group decreased, and the number of times of crossing the platform increased significantly ( p <0.01 or p <0.05). The above indicates that N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly improve the spatial memory ability of AD mice.
[0042] 5. Effects on the contents of inflammatory factors TNF-α, IL-1β, and IL-6 in the mouse brain tissue The results of the effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the contents of inflammatory factors TNF-α, IL-1β, and IL-6 in the brain tissue of AD mice are shown in Figure 5 the figure.
[0043] The results showed that, compared with the control group, the contents of TNF-α, IL-1β, and IL-6 in the brain tissue of the mice in the model group increased significantly ( p <0.001), suggesting that the inflammatory factors in AD mice induced by D-galactose combined with AlCl3 increased. Compared with the model group, the contents of TNF-α and IL-6 in the brain tissue of the mice in the positive drug group and the N1-dihydrocaffeoyl-N10-caffeoylspermidine group decreased significantly ( p <0.001 or p <0.01), and the content of IL-1β in the positive drug group decreased significantly ( p <0.001), and the content of IL-1β in the N1-dihydrocaffeoyl-N10-caffeoylspermidine group tended to decrease but there was no statistical difference. The above suggests that the positive drug and N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly reduce the levels of inflammatory factors in the brain tissue of AD mice.
[0044] 6. Effects on the contents of oxidative stress factors SOD and GSH in the mouse brain tissue The results of the effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the contents of oxidative stress factors SOD and GSH in the brain tissue of AD mice are shown in Figure 6 the figure.
[0045] The results showed that, compared with the control group, the contents of SOD and GSH in the brain tissue of the mice in the model group decreased significantly ( p <0.001). Compared with the model group, the positive drug group could significantly increase the SOD content of AD mice ( p(<0.01). There was an obvious upward trend in the contents of SOD and GSH in the brain tissues of the mice in the N1-dihydrocaffeoyl-N10-caffeoylspermidine group, but there was no statistical difference. The above suggests that the positive drug and N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the levels of oxidative stress factors in the brain tissues of AD mice.
[0046] 7. Effects on Aβ in mouse brain tissues 40 and Aβ 42 Contents The effects of N1-dihydrocaffeoyl-N10-caffeoylspermidine on the contents of Aβ 40 and Aβ 42 in the brain tissues of AD mice are shown as follows. Figure 7 Shown below.
[0047] The results showed that compared with the control group, the contents of Aβ 40 and Aβ 42 in the brain tissues of the mice in the model group increased significantly ( p <0.001 or p <0.01), suggesting that the pathogenesis of learning and memory impairment in AD mice induced by D-galactose combined with AlCl3 may be related to Aβ 40 and Aβ 42 . Compared with the model group, the contents of Aβ 40 and Aβ 42 in the brain tissues of the mice in the positive drug group and the N1-dihydrocaffeoyl-N10-caffeoylspermidine group decreased significantly ( p <0.001 or p <0.01). The results indicate that the protective effects of the positive drug and N1-dihydrocaffeoyl-N10-caffeoylspermidine on learning and memory impairment in AD mice may be related to their reduction of the contents of Aβ 40 and Aβ 42 in the brain tissues.
[0048] During the whole process of drug administration to animals, no mice died, and there were no abnormal conditions in the appearance and behavior of the mice.
[0049] 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.
[0050] The foregoing description of the disclosed embodiments enables those skilled in the art to practice or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. Application of N1-dihydrocaffeoyl-N10-caffeoyl spermidine in the preparation of drugs for the prevention and treatment of AD.
2. The use according to claim 1, characterized in that: N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the spontaneous alternation reaction rate of Alzheimer's disease mice in the Y-maze test, that is, improve their working memory ability.
3. The use according to claim 1, characterized in that: N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the ability of Alzheimer's disease mice to recognize new objects, that is, improve their learning ability.
4. The use according to claim 1, characterized in that: N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly reduce the escape latency of Alzheimer's disease mice in the Morris water maze test and increase the number of times they cross the platform, that is, improve their spatial memory ability.
5. The use according to claim 1, characterized in that: N1-dihydrocaffeoyl-N10-caffeoyl spermidine significantly reduces Aβ in brain tissue of Alzheimer's disease mice 40 and Aβ 42 content.
6. The use according to claim 1, characterized in that: N1-dihydrocaffeoyl-N10-caffeoyl spermidine can significantly reduce the levels of inflammatory factors TNF-α, 1L-1β and 1L-6 in the brain tissue of Alzheimer's disease mice.
7. The use according to claim 1, characterized in that: N1-dihydrocaffeoyl-N10-caffeoylspermidine can significantly increase the levels of SOD and GSH in the brain tissue of Alzheimer's disease mice.
8. A drug for preventing and treating Alzheimer's disease, characterized in that: Including N1-dihydrocaffeoyl-N10-caffeoyl spermidine.
9. The drug according to claim 8, characterized in that The dosage form is a pharmaceutically acceptable oral dosage form, external patch or injection dosage form.