R is N, N-acetyl-Napos; application of caffeoyl butanediamine in preparation of anti-aging drugs, health care products or functional food

Abstract

The invention discloses an application of N-acetyl-N '-caffeoyl butanediamine in preparation of anti-aging drugs, health care products or functional foods. Belongs to the technical field of biological medicine. In-vitro cell experiments prove that N-acetyl-N '-caffeoyl butanediamine has an anti-aging effect, and can significantly inhibit and reduce the number of senescent cells of astrocytes induced by D-galactose. The N-acetyl-N '-caffeoyl butanediamine is used for preparing the medicine, the health care product and / or the functional food for delaying, preventing and / or treating the aging, a new choice is provided for resisting the aging, and the N-acetyl-N'-caffeoyl butanediamine has important practical application value in the fields of medicine and aging resistance.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and more specifically relates to the application of N-acetyl-N'-caffeoylputrescine in the preparation of anti-aging drugs, health products or functional foods. Background Art

[0002] According to statistics of the World Health Organization (WHO), the global population aged 60 and above will exceed 2.1 billion by 2050, accounting for 22% of the total population. The intensification of population aging has led to a sharp increase in the burden of aging-related diseases. Aging is not only a natural result of extended lifespan, but also a core driving factor for shortened healthspan, and there is an urgent need to develop efficient and safe intervention strategies. Currently, the main anti-aging interventions are synthetic drugs. For example, Senolytics (such as fisetin) can selectively eliminate senescent cells, but there are risks of bone marrow suppression and hepatotoxicity and nephrotoxicity; NAD+ precursors (such as NMN) can delay aging by activating Sirtuins, but have low bioavailability and high costs; mTOR inhibitors (such as everolimus) can extend the lifespan of model organisms, but long-term use leads to immunosuppression and abnormal glucose metabolism. Natural drugs, due to their chemical diversity and high safety, have become a key direction in the research and development of anti-aging drugs.

[0003] N-acetyl-N'-caffeoylputrescine of the present invention is a phenolic amide compound naturally present in medicinal and edible homologous traditional Chinese medicines such as Lycium barbarum in the Solanaceae family, and there is currently no relevant record of N-acetyl-N'-caffeoylputrescine being used for anti-aging. Summary of the Invention

[0004] In view of this, the present invention provides the application of N-acetyl-N'-caffeoylputrescine in the preparation of drugs, health products or functional foods for preventing and treating aging. Through preliminary in vitro cell experiments, the present invention found that N-acetyl-N'-caffeoylputrescine has an obvious anti-aging effect, and it can significantly inhibit and reduce the number of senescent cells in D-galactose-induced astrocytes. Further, developing it into a drug capable of delaying, preventing and / or treating aging, or a health product or functional food capable of delaying, preventing and / or treating aging will have great practical application value.

[0005] N-acetyl-N'-caffeoylputrescine, with the molecular formula C 15 H 20 N2O4, the English name is N-acetyl-N'-caffeoylputrescine, the molecular weight is 292.14, and its chemical structural formula is shown in Formula (1).

[0006] Formula (1).

[0007] To achieve the above object, the present invention adopts the following technical solutions.

[0008] Use of N-acetyl-N'-caffeoyl succinyl diamide in the preparation of a medicament for preventing and treating aging, or in the preparation of a health care product or functional food for preventing and treating aging.

[0009] Furthermore, N-acetyl-N'-caffeoyl succinyl diamide can significantly inhibit and reduce the number of D-galactose-induced senescent astrocytes.

[0010] An anti-aging medicament, characterized by comprising N-acetyl-N'-caffeoyl succinyl diamide.

[0011] Furthermore, the dosage form is an orally administrable dosage form, external patch or injection dosage form permitted in pharmacy.

[0012] A health care product for anti-aging, comprising N-acetyl-N'-caffeoyl succinyl diamide.

[0013] A functional food for anti-aging, comprising N-acetyl-N'-caffeoyl succinyl diamide.

[0014] From the above technical solutions, it can be seen that, compared with the prior art, the beneficial effects achieved by the present invention are as follows: in the range of a dose of 0.1 to 10 μM given to experimental cells, N-acetyl-N'-caffeoyl succinyl diamide can significantly inhibit and reduce the number of D-galactose-induced senescent astrocytes. The above all confirm that N-acetyl-N'-caffeoyl succinyl diamide has an anti-aging effect and can be used in the preparation of medicaments, health care products and / or functional foods for delaying, preventing and / or treating aging. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] 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, other drawings can be obtained according to the provided drawings without creative efforts.

[0016] Appendix Figure 1 Microscopic photographing results of the β-galactosidase staining experiment to investigate the anti-aging effect of N-acetyl-N'-caffeoyl succinyl diamide on astrocytes (Control is the normal group, Model is the model group, NANCP-10 is the group of N-acetyl-N'-caffeoyl succinyl diamide with a concentration of 10 μM, NANCP-1 is the group of N-acetyl-N'-caffeoyl succinyl diamide with a concentration of 1 μM, NANCP-0.1 is the group of N-acetyl-N'-caffeoyl succinyl diamide with a concentration of 0.1 μM).

[0017] Appendix Figure 2 ImageJ statistical results of the anti - aging effect of N - acetyl - N'-caffeoylbutanediamide on astrocytes by β - galactosidase staining experiment (Control is the normal group, Model is the model group, NANCP - 10 is the group of N - acetyl - N'-caffeoylbutanediamide with a concentration of 10 μM, NANCP - 1 is the group of N - acetyl - N'-caffeoylbutanediamide with a concentration of 1 μM, NANCP - 0.1 is the group of N - acetyl - N'-caffeoylbutanediamide with a concentration of 0.1 μM; compared with the normal group, ### p <0.001; compared with the model group, *** p <0.001). Detailed implementation manners

[0018] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with 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 belong to the scope of protection of the present invention.

[0019] The N - acetyl - N'-caffeoylbutanediamide used in the following examples is the compound shown in the above formula (1), and can be obtained through commercial purchase or experimental self - preparation.

[0020] The medicaments required for the present invention are conventional experimental medicaments, purchased from commercial channels; the experimental methods not mentioned are conventional experimental methods, and will not be elaborated one by one here. Example 1

[0021] An anti - aging drug, in an oral dosage form, comprising N - acetyl - N'-caffeoylbutanediamide. Example 2

[0022] An anti - aging drug, in an injection dosage form, comprising N - acetyl - N'-caffeoylbutanediamide. Example 3

[0023] An anti - aging drug, in an external patch dosage form, comprising N - acetyl - N'-caffeoylbutanediamide. Example 4

[0024] An anti - aging health care product, comprising N - acetyl - N'-caffeoylbutanediamide. Example 5

[0025] An anti - aging functional food, comprising N - acetyl - N'-caffeoylbutanediamide.

[0026] Experiment 1 The following cell experiments further illustrate the effects of the above Examples 1 to 5.

[0027] I. Cell experiment design A D-galactose-induced astrocyte senescence model was used. After administering N-acetyl-N'-caffeoylputrescine, the anti-aging effect of N-acetyl-N'-caffeoylputrescine was evaluated by β-galactosidase staining experiment.

[0028] II. Experimental procedure 1. Experimental cells C8-D1A mouse cerebellar astrocytes were taken and cultured in a 37 °C, 5% saturated humidity CO2 incubator, and the medium used was the special medium for C8-D1A cells.

[0029] 2. Experimental method A D-galactose-induced astrocyte senescence model was used. The astrocytes were seeded at 1×10 5 cells / well in a 24-well plate, and the experiment could be carried out when the cells grew to cover 50% of the bottom of the dish.

[0030] Media containing 50 mM D-galactose were prepared, and then NANCP was added to this medium to make its concentrations 10, 1, and 0.1 μM respectively, corresponding to the high, medium, and low concentration groups of NANCP. In addition, a medium without 50 mM D-galactose was set as the normal group, and a medium containing 50 mM D-galactose was set as the model group. After culturing for 72 h, the medium was removed, and the cells were washed twice with 1 mL PBS and the PBS was aspirated completely. 0.25 mL of β-galactosidase staining fixative was added to each well, and the cells were fixed at room temperature for 15 min. After the fixative was aspirated and the cells were washed three times with PBS, the PBS was aspirated completely. 0.25 mL of staining working solution was added to each well, covered with plastic wrap, and incubated overnight at 37 °C. The next day, the staining working solution was removed, 0.25 mL of PBS was added, and the cells were observed and photographed under a microscope.

[0031] 3. Data processing The data of the present invention were processed using ImageJ and Graphpad Prism for data analysis and statistics. ImageJ was used to analyze the stained photos, and the number of positive senescent cells in each group was represented by the area of green senescent cells at the same magnification. 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 the difference was considered statistically significant when p <0.05 was used as the standard.

[0032] III. Experimental results The results of the effect of N-acetyl-N'-caffeoyl succinamide on the senescence of astrocytes are shown in Figure 1 and Figure 2 as follows.

[0033] After culturing astrocytes in each group for 72 h, compared with the normal group, the number of positive senescent cells in the model group increased significantly ( p < 0.001). Compared with the model group, the number of positive senescent cells in all drug-administered groups decreased significantly ( p < 0.001), and it showed that the higher the drug administration concentration, the fewer the number of positive senescent cells. The above indicates that N-acetyl-N'-caffeoyl succinamide has a significant inhibitory effect on D-galactose-induced astrocyte senescence.

[0034] The various embodiments in this specification are described in a progressive manner. Each embodiment focuses on the differences from other embodiments. The same or similar parts among the various embodiments can be referred to each other.

[0035] 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 these embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Use of N-acetyl-N'-caffeoyl succinyl diamide in the preparation of drugs for preventing and treating aging, or in the preparation of health care products or functional foods for preventing and treating aging.

2. The application according to claim 1, characterized in that, N-acetyl-N'-caffeoyl succinyl diamide can significantly inhibit and reduce the number of senescent cells of astrocytes induced by D-galactose.

3. An anti-aging drug, characterized in that, It includes N-acetyl-N'-caffeoyl succinyl diamide.

4. The drug according to claim 3, wherein, The dosage form is an orally administrable dosage form, external patch or injection dosage form permitted in pharmacy.

5. An anti-aging health product, characterized in that, It includes N-acetyl-N'-caffeoyl succinyl diamide.

6. A functional food for anti-aging, characterized in that, It includes N-acetyl-N'-caffeoyl succinyl diamide.

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