Application of sennoside A in medicine for preventing and / or treating retina light injury

Abstract

The invention provides application of sennoside A in a medicine for preventing and / or treating retina light injury, and belongs to the technical field of eye medicine manufacturing. The drug effect verification of the sennoside A is carried out by taking a retina photoinjury mouse model as an experimental subject, and the result shows that the sennoside A can improve the cytopathic morphology of an outer nuclear layer and an inner nuclear layer of a retina, reduce the apoptosis of retinal cells, reduce the oxidative stress level in a body and inflammatory response in the body and improve the oxidation resistance. Therefore, sennoside A has a good protection effect on retina photoinjury. Therefore, the invention provides an application of sennoside A in a medicine for preventing and / or treating retina light damage and / or a product for relieving a visual fatigue function.

Description

Technical Field

[0001] The present invention belongs to the technical field of ophthalmic drug manufacturing, and specifically relates to the application of sennoside A in the preparation of drugs for preventing and / or treating retinal light injury. Background Art

[0002] Sennoside A (SA) is the main active ingredient of anthraquinones in rhubarb and is widely used as a stimulant laxative, weight loss drug or dietary supplement in China and other Asian countries. At the same time, SA also has antibacterial, enzyme activity inhibition, HIV-1 replication inhibition, restoration of intestinal flora balance, improvement of glucose metabolism in obese mice, and improvement of liver steatosis in non-alcoholic fatty liver mice. Recently, research reports have shown that SA is also active against various tumors or cancers, such as pancreatic cancer and liver cancer. Currently, there is no report on the use of SA for retinal light injury repair. Summary of the Invention

[0003] In view of this, the purpose of the present invention is to provide a new use of sennoside A, that is, the application of sennoside A in the preparation of drugs for preventing and / or treating retinal light injury.

[0004] The present invention provides the application of sennoside A in the preparation of drugs for preventing and / or treating retinal light injury and / or products with the function of relieving visual fatigue.

[0005] Preferably, the diseases of retinal light injury include at least one of the following: myopia, retinal detachment, retinal vascular lesions, macular degeneration, eye fatigue and blurred vision.

[0006] Preferably, the diseases of retinal light injury include at least one of the following lesions: morphological changes of cells in the outer nuclear layer and inner nuclear layer of the retina, apoptosis of retinal cells, increased oxidative stress level in the body, enhanced inflammatory response in the body and decreased antioxidant capacity.

[0007] Preferably, the retinal light injury is caused by illumination with acute / chronic natural light, ultraviolet light or blue light.

[0008] Preferably, the illumination time is more than 20 h.

[0009] Preferably, the dosage form of the drug includes at least one of the following: tablets, powders, oral liquids, capsules, granules; The types of the products include at least one of the following: soft capsules, beverages and gummies.

[0010] Preferably, the drug includes pharmaceutically / food scientifically acceptable excipients; the product includes edible excipients; The pharmaceutically acceptable excipients or edible excipients include at least one of the following: diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, fragrances, sweeteners, nutritional agents, and flavor enhancers.

[0011] Preferably, the concentration of sennoside A in the drug is not less than 2.24 μM.

[0012] The present invention provides the use of sennoside A in the preparation of an ALDH2 enzyme agonist.

[0013] Preferably, the concentration of sennoside A in the ALDH2 enzyme agonist is not less than 2.24 μM.

[0014] The present invention provides the use of sennoside A in the preparation of a drug for preventing and / or treating retinal light damage and / or a product with the function of relieving visual fatigue. First, the present invention uses 40 compounds obtained by molecular docking virtual screening as test objects to carry out the test of the response intensity of the ALDH2 target. The results show that sennoside A (C3) exhibits the strongest activation level of ALDH2 enzyme activity, and the cell fluorescence intensity is 10 times higher than that of the blank control group. At the same time, the present invention also uses a light-damaged mouse model as the object to verify the efficacy of sennoside A. The results show that compared with the model group, both the low dose and high dose of sennoside A can well improve the morphological changes of the outer nuclear layer of the retina, increase the thickness of the outer nuclear layer and the inner nuclear layer, and the protective effect of sennoside A on the outer nuclear layer of the retina is equivalent to that of the positive drug lutein; the results of TUNEL fluorescence staining show that both the low dose and high dose of sennoside A can better improve the apoptosis of retinal cells caused by light, and the protective effect of the low dose of sennoside A on retinal cell apoptosis is equivalent to that of the positive drug lutein; the results of plasma MDA level measurement show that the high dose of sennoside A can significantly reduce the level of lipid peroxidation in the body, indicating that sennoside A has a protective effect on cell oxidative stress damage; the results of plasma interleukin 6 measurement show that the high dose of sennoside A can significantly reduce the level of interleukin 6 (IL-6) in the body, indicating that sennoside A has an improving effect on the cell inflammatory response caused by light; the results of plasma total antioxidant capacity level measurement show that the high dose of sennoside A can significantly improve the antioxidant capacity in the body, indicating that sennoside A can improve the total antioxidant capacity of cells. Based on the above verification results, it can be seen that the sennoside A has a good effect on improving retinal light damage, can be used for the prevention and / or treatment of retinal light damage-related diseases, and at the same time broadens the medical application field of sennoside A and improves the medicinal value of sennoside A. Description of the Drawings

[0015] Figure 1Drug screening results based on the fluorescence response of ALDH2; A is the virtual docking mode diagram of sennoside A and ALDH2; B is the relative quantitative diagram of fluorescence intensity for the increase in ALDH2 enzyme activity induced by natural drugs. Figure 2 Confocal fluorescence imaging of HepG2 cells treated with sennoside A; A is a representative image, scale bar = 60 μm; B is the quantitative curve of fluorescence intensity of HepG2 cells. Figure 3 H&E staining of mouse retina; A is the H&E staining of mouse retina tissue and the thickness diagrams of the outer nuclear layer and inner nuclear layer of the retina, scale bars: 500 μm and 20 μm; B and C are the quantitative diagrams of the thickness of the outer nuclear layer and inner nuclear layer of the retina, the number of mice n = 5 - 6; Note: ## P <0.01, P <0.001; Figure 4 TUNEL staining of apoptotic cells in mouse retina; A is the TUNEL fluorescence staining of mouse retina, DAPI blue fluorescence represents the nucleus, TUNEL red fluorescence represents apoptotic cells, scale bars: 500 μm and 200 μm; B is the quantitative diagram of fluorescence intensity of apoptotic cells in the retina, the number of mice n = 5 - 6; Note: ## P <0.01, P <0.001; Figure 5 Content of malondialdehyde in mouse plasma, the number of mice n = 5; Note: # P <0.05, ## P <0.01, ns indicates no significant difference compared with the model group. Figure 6 IL-6 level in mouse plasma, the number of mice n = 6 - 7; Note: # P <0.05, P <0.001; Figure 7 Total antioxidant capacity (T-AOC) in mouse plasma, the number of mice n = 5; Note: # P <0.05; There is a tendency for the total antioxidant capacity of mice in the high-dose sennoside A administration group to increase compared with the model group, P The value is 0.054. Specific implementation methods

[0016] The present invention provides the application of sennoside A in the preparation of drugs for preventing and / or treating retinal light damage and / or products with the function of relieving visual fatigue.

[0017] In the present invention, the molecular formula of the sennoside A: C 42 H38 O 20 , molecular weight: 862.74, and the structural formula is shown in Formula I: Formula I.

[0018] In the embodiment of the present invention, the sennoside A was purchased from MCE, product number: HY-N0365. Usage method: Sennoside A was dissolved in DMSO.

[0019] In the present invention, the diseases of retinal light damage preferably include at least one of the following: myopia, retinal detachment, retinal vascular disease, macular degeneration, eye fatigue, and blurred vision. The myopia, retinal detachment, and retinal vascular disease caused by retinal light damage refer to that long-term exposure to high-intensity blue light or ultraviolet light will cause photoreaction in retinal cells, generate free radicals, and then damage retinal cells. This damage will affect the function of the retina, may lead to vision decline, and then develop into myopia. The macular degeneration refers to that long-term exposure to strong light, especially blue light, may cause damage to the cells in the macular area, thus triggering macular degeneration. This disease usually manifests as blurred central vision, distortion, or the appearance of dark spots. The retinal detachment refers to that retinal light damage may weaken the adhesion force between retinal layers, thus increasing the risk of retinal detachment. Retinal detachment is a serious disease. If not treated in time, it may lead to permanent blindness. The retinal vascular disease is that retinal light damage affects retinal blood vessels, causes damage to the blood vessel wall, and thus triggers retinal vascular disease. The retinal light damage is caused by acute / chronic natural light, ultraviolet light, or blue light illumination, for example, caused by the light emitted by natural light or electronic devices. The illumination time is preferably more than 20 h. It can be 22 - 30 h, or it can be 26 h.

[0020] In the embodiments of the present invention, the mouse model of retinal light injury of the experimental subjects is caused by light of 8000-10000 Lux. The irradiation time of the light is preferably 22-26 h. In a specific embodiment of the present invention, the treatment condition can be continuous irradiation with light of 9000 Lux for 24 h. The mouse model of retinal light injury preferably includes at least one of the following lesions: morphological changes of cells in the outer nuclear layer and inner nuclear layer of the retina, apoptosis of retinal cells, increased oxidative stress level in the body, enhanced inflammatory response in the body, and decreased antioxidant capacity. The morphological changes of cells in the outer nuclear layer and inner nuclear layer of the retina refer to morphological changes such as loosening and reduced thickness in the outer nuclear layer and inner nuclear layer of the mouse retina after light damage treatment. The apoptosis of retinal cells is an increase in the number of red fluorescent apoptotic cells after TUNEL fluorescence staining of mouse retinal cells after light treatment. The increase in oxidative stress level in the body refers to using malondialdehyde in the plasma of model mice as an index of lipid peroxidation to reflect the degree of cell membrane lipid peroxidation. Compared with the control group, the content of malondialdehyde in the plasma after light treatment is significantly increased, indicating an increase in the lipid peroxidation level of model mice. The enhanced inflammatory response in the body refers to using the level of IL-6 to reflect the level of inflammatory response. The inflammatory response mediated by the level of IL-6 in the body of mice after light treatment increases. The decrease in antioxidant capacity refers to the total antioxidant level composed of various antioxidant substances and antioxidant enzymes, etc. To protect cells from oxidative stress damage caused by reactive oxygen free radicals, the total antioxidant capacity can be used to evaluate the antioxidant capacity of bioactive substances. The total antioxidant capacity level of mice after light treatment is significantly decreased.

[0021] In the present invention, the low-dose group (100 mg / kg) and high-dose group (200 mg / kg) of sennoside A were set to verify its efficacy on the mouse model of retinal light injury. The results showed that the H&E histopathological results showed that both the low dose and high dose of sennoside A could well improve the morphological changes of the outer nuclear layer of the retina, increase the thickness of the outer nuclear layer and inner nuclear layer under light conditions, and the protective effect of sennoside A on the outer nuclear layer of the retina was equivalent to that of the positive drug lutein; the TUNEL staining results of retinal apoptotic cells showed that both the low dose and high dose of sennoside A could better improve the apoptosis of retinal cells caused by light, and the protective effect of the low dose of sennoside A on retinal cell apoptosis was equivalent to that of the positive drug lutein; the determination results of plasma MDA level showed that the high dose of sennoside A could significantly reduce the lipid peroxidation level in the body, indicating that sennoside A has a protective effect on cell oxidative stress damage; the determination results of plasma interleukin 6 showed that the high dose of sennoside A could significantly reduce the level of IL-6 in the body, indicating that sennoside A has an improving effect on the cell inflammatory response caused by light; the determination results of plasma total antioxidant capacity (T-AOC) level showed that the high dose of sennoside A could significantly improve the antioxidant capacity in the body, indicating that sennoside A can improve the total antioxidant capacity of cells In the present invention, ALDH2 is an aldehyde dehydrogenase and is crucial in the catabolism of exogenous and endogenous toxic aldehydes related to oxidative stress-induced lipid peroxidation. Research shows that an increase in the expression of ALDH2 can improve oxidative stress and inflammatory damage in the retina, playing a role in protecting the structure and function of the retina. To clarify the mechanism of sennoside A in preventing and treating retinal light damage, the present invention investigated the effect of sennoside A on the activity of ALDH2 enzyme. The results showed that sennoside A highly responds to the ALDH2 target and protects against retinal light damage by upregulating the activity of the ALDH2 enzyme. Therefore, the present invention provides the application of sennoside A in the preparation of drugs for treating retinal light damage diseases and / or products with the function of relieving visual fatigue.

[0022] In the present invention, the dosage form of the drug includes at least one of the following: tablets, powders, oral liquids, capsules, granules; the types of the product include at least one of the following: soft capsules, beverages, and gummies. The drug includes pharmaceutically / food scientifically acceptable excipients; the product includes edible excipients; the pharmaceutically acceptable excipients or edible excipients include at least one of the following: diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, fragrances, sweeteners, nutritional agents, and flavor enhancers. The concentration of sennoside A in the drug or product is preferably not less than 2.24 μM, and preferably 10 - 50 μM.

[0023] In the examples of the present invention, the preferred dosage of sennoside A for drug administration to mice is 100 - 200 mg / kg. The preferred dosage of sennoside A for human administration is 10.99 - 21.98 mg / kg.

[0024] In view of sennoside A having the ability to upregulate the activity of ALDH2 enzyme in cells, the present invention provides the application of sennoside A in the preparation of an ALDH2 enzyme agonist.

[0025] In the present invention, the half-maximal effective concentration (EC 50 ) of sennoside A is 2.24 μM. The concentration of sennoside A in the ALDH2 enzyme agonist is preferably not less than 10 mM, preferably 12 - 20 mM, and can be 15 - 18 mM. The ALDH2 enzyme agonist can be applied to upregulate the activity of ALDH2 enzyme in the HepG2 cell line.

[0026] The following combines examples to elaborate in detail on the application of sennoside A provided by the present invention in drugs for preventing and / or treating retinal light damage, but they should not be construed as limiting the protection scope of the present invention.

[0027] Example 1 Screening of ALDH2-responsive drugs based on HepG2 cells 1. Experimental methods: 1.1 Cell culture and subculture The HepG2 cell line was purchased from the National Authentication Cell Culture Bank of the Chinese Academy of Sciences. Cells were cultured in complete medium (Dulbecco's modified Eagle medium + 10% fetal bovine serum + 1% antibiotics) and incubated in an incubator at 37 °C and 5% CO2. When the cell density reached 80%, cells were carefully collected for subculture to ensure exponential growth of the cells. In all cell experiments, when the passage number was < 25, all cells remained mycoplasma-free.

[0028] 1.2 Drug screening based on ALDH2 response Forty compounds that were potentially bind to ALDH2 enzyme were obtained by virtual screening of molecular docking. The forty compounds were respectively incubated with HepG2 cells. The drug solutions were provided by MCE with a concentration of 10 mM. Cells were treated with a drug concentration of 10 μM overnight, and incubated with 0.5 mM azidoacetaldehyde (AAN3) as the substrate for ALDH2 enzyme reaction for 8 h. Then cells were fixed with 4 °C formaldehyde and photographed by confocal fluorescence microscopy after rhodamine (RHO) staining. Images were analyzed by "ImageJ" software, and the fluorescence intensity was quantified by densitometry. The cell fluorescence intensity was positively correlated with ALDH2 activity.

[0029] 1.3 Quantitative determination of the response intensity of sennoside A to ALDH2 target HepG2 cells were treated with different concentrations of sennoside A overnight, then incubated with 0.5 mM AAN3 for 8 h, fixed with 4 °C methanol, and then stained with RHO. Photographs were taken using a confocal fluorescence microscope, images were analyzed by "ImageJ" software, and the fluorescence intensity was quantified by densitometry. Quantitative analysis of the fluorescence intensity of HepG2 cells was performed, and the dose-effect analysis of sennoside A was carried out using Nonlin fitting. The signal intensity was normalized to the blank group.

[0030] 2. Experimental results: 2.1 Drug screening experiment based on ALDH2 response First, compounds that interacted with ALDH2 were virtually screened by molecular docking. Through docking prediction, the results showed a strong interaction between sennoside A and the allosteric site of ALDH2 ( Figure 1 In A, the docking pocket of ALDH2 is ribbon-shaped, and sennoside A is skeleton-shaped). Subsequently, 40 compounds of A2-3A2 (see Table 1) were screened by cell incubation experiments. After confocal fluorescence detection and analysis, it was shown that sennoside A (C3) exhibited the strongest activation level of ALDH2 enzyme activity, and the cell fluorescence intensity was 10 times higher than that of the blank control group (Figure 1 In B), this result is consistent with the docking prediction.

[0031] Table 1 Information table of 40 compounds of A2 - 3A2

[0032] 2.2 Determination of the half - maximal effective concentration of sennoside A in response to the ALDH2 target After treating HepG2 cells with different concentrations of sennoside A, confocal fluorescence microscopy was used to take pictures and analyze. The signal intensity was normalized to the blank group, and a dose - response analysis was performed using Nonlin fitting.

[0033] The imaging results showed that sennoside A significantly up - regulated the enzyme activity of ALDH2 ( Figure 2 In A), and the half - maximal effective concentration (EC 50 ) of sennoside A was 2.24 μM ( Figure 2 In B).

[0034] Example 2 Drug administration experiment on a mouse model of light damage 1. Experimental method 1.1 Experimental animals 8 - week - old male BALB / c mice were purchased from Zhejiang Vital River Laboratory Animal Technology Co., Ltd. Before the start of the experiment, all mice were adaptively fed under a 12:12 h light / dark cycle in an animal house at a certain temperature and humidity for 1 week, and provided with normal food and drinking water every day. All experimental operations followed the guidelines for animal care and use of the Animal Research Institute of Zhejiang University.

[0035] 1.2 Construction of a mouse model of light damage and drug administration treatment A light box with a length of 108 cm, a width of 50 cm, and a height of 72 cm was self-made. The light intensity was detected by a lux meter to be 8500 - 10000 Lux. After eye examination of the mice, mice with normal eyes were randomly divided into a control group (12 mice), a model group (10 mice), a lutein group (100 mg / kg, 10 mice), a low-dose sennoside A group (100 mg / kg, 10 mice), and a high-dose sennoside A group (200 mg / kg, 10 mice). Lutein and sennoside A were suspended in a 5% sodium carboxymethylcellulose (CMC-Na) solution and administered by gavage once a day. Mice in the blank and model groups were gavaged with an equal volume of 5% CMC-Na. Administration continued for 10 days. After 10 days, the mice in the model group, lutein group, low-dose sennoside A group, and high-dose sennoside A group were dark-treated for 36 h, then atropine ophthalmic gel was applied to both eyes of the mice to dilate the pupils. The mice were then placed under light with an intensity of 8000 - 10000 Lux for 24 h, while the mice in the blank group were raised in a normal environment. After the light exposure ended, blood was collected by enucleating the eyes of each group of mice, and the eye tissues were collected for relevant detections in subsequent experiments.

[0036] 1.3 The experimental instruments are shown in Table 2.

[0037] Table 2 Description of instrument sources

[0038] 1.4 The experimental consumables and reagents are shown in Table 3.

[0039] Table 3 Description of sources of experimental consumables and reagents

[0040] 1.5 Histopathological examination For each group, 5 - 6 mouse eye tissues were subjected to hematoxylin-eosin staining (H&E) and TUNEL fluorescence staining for apoptotic cells, and the histopathological changes in the mouse eye tissues were observed using an optical microscope (completed by Wuhan Sevier Biotechnology Co., Ltd.).

[0041] 1.6 Determination of MDA level in mouse plasma Mouse blood was collected into anticoagulant tubes and centrifuged at 3000 rpm for 10 min at 4°C to collect the upper plasma. The content of MDA was determined according to the method provided by the kit manufacturer.

[0042] 1.7 Statistical analysis Graphs were plotted and statistical analyses were performed using Prism 8 software. All data were expressed as mean ± standard error of the mean (SEM±). Independent sample t-tests were used to analyze the differences between two groups, and one-way Anova was used for the others. P <0.05 indicated that the difference was statistically significant.

[0043] 2. Experimental results 2.1 H&E histopathological evaluation The retina is the most crucial part of the eye, and its hierarchical structure includes the retinal ganglion cell layer, the inner nuclear layer of the retina, the outer nuclear layer of the retina, and the retinal pigment epithelium. The outer nuclear layer of the retina is mainly composed of photoreceptor cells such as rod cells and cone cells, which can receive light stimuli and convert light signals into electrical signals. The inner nuclear layer of the retina contains different types of neuron cells that can convert electrical signals into nerve impulses. It can be seen that the inner / outer nuclear layer cells of the retina play an important role in the reception and conduction of visual signals. According to the results of retinal H&E staining, it was found that light damage caused morphological changes such as loosening and reduced thickness in the outer nuclear layer and inner nuclear layer of the retinas of mice in the model group, indicating that light caused damage to retinal cells ( Figure 3 in A). While both low-dose and high-dose sennoside A could well improve the morphological changes in the outer nuclear layer of the retina and increase the thickness of the outer nuclear layer and inner nuclear layer under light conditions ( Figure 3 in B-C), and the protective effect of sennoside A on the outer nuclear layer of the retina was comparable to that of the positive drug lutein, indicating that sennoside A has a good effect on improving retinal light damage.

[0044] 2.2 TUNEL staining of apoptotic cells in the retina According to the results of TUNEL fluorescence staining of apoptotic cells in retinal tissues, it was found that light caused a large number of apoptotic cells in the retinas of mice in the model group (red fluorescence, Figure 4 in A), while both low-dose and high-dose sennoside A could better improve the cell apoptosis caused by light in the retina, and the protective effect of high-dose sennoside A on retinal cell apoptosis was comparable to that of the positive drug lutein ( Figure 4 in A and B).

[0045] 2.3 Determination of plasma MDA level Plasma malondialdehyde (MDA) is one of the main products of cell membrane lipid peroxidation, and its content can be used as an index of lipid peroxidation to reflect the degree of cell membrane lipid peroxidation. In this experiment, it was found that light led to an increase in the level of lipid peroxidation in the model mouse group, while high-dose sennoside A could significantly reduce the level of lipid peroxidation in the body, indicating that sennoside A has a protective effect on cell oxidative stress damage ( Figure 5 ).

[0046] 2.4 Determination of Plasma Interleukin-6 (IL-6) Level Interleukin is a class of cytokines produced by various cells and acting on various cells, which plays an important regulatory role. It plays an important role in transmitting information, activating and regulating immune cells, and mediating inflammatory responses. In this experiment, it was found that light could cause an increase in the plasma IL-6 level in the model group of mice, indicating that light led to an increase in the inflammatory response mediated by IL-6 in the body, while high-dose sennoside A could significantly reduce the level of IL-6 in the body, suggesting that sennoside A has an improving effect on the cell inflammatory response caused by light ( Figure 6 ).

[0047] 2.5 Determination of Plasma Total Antioxidant Capacity (T-AOC) Level Plasma total antioxidant capacity (T-AOC) refers to the total antioxidant level composed of various antioxidant substances and antioxidant enzymes, etc. To protect cells from oxidative stress damage caused by reactive oxygen free radicals, the total antioxidant capacity can therefore be used to evaluate the antioxidant capacity of bioactive substances. This experiment showed that light led to a decrease in the total antioxidant capacity level in the model group of mice, while high-dose sennoside A had a tendency to increase the antioxidant capacity in the body. It is indicated that sennoside A can increase the total antioxidant capacity of cells ( Figure 7 ).

[0048] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. Application of sennoside A in preparing a drug for preventing and / or treating retinal light injury and / or a product with the function of relieving visual fatigue.

2. The application according to claim 1, wherein The diseases of retinal light injury include at least one of the following: myopia, retinal detachment, retinal vascular disease, macular degeneration, eye fatigue, and blurred vision.

3. The application according to claim 1, characterized in that, The diseases of retinal light injury include at least one of the following lesions: morphological changes of cells in the outer nuclear layer and inner nuclear layer of the retina, apoptosis of retinal cells, increased oxidative stress level in the body, enhanced inflammatory response in the body, and decreased antioxidant capacity.

4. The application according to claim 1, characterized in that, The retinal light injury is caused by illumination with acute or chronic natural light, ultraviolet light, or blue light.

5. The application according to claim 4, wherein The cumulative time of the illumination is more than 20 h.

6. The application according to claim 1, wherein, The dosage form of the drug includes at least one of the following: tablets, powders, oral liquids, capsules, granules; The types of the product include at least one of the following: soft capsules, beverages, and gummies.

7. The application according to claim 1, wherein The drug includes pharmaceutically acceptable excipients; the product includes excipients meeting edible requirements; The pharmaceutically acceptable excipients or excipients meeting edible requirements include at least one of the following: diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption promoters, surfactants, adsorption carriers, lubricants, fragrances, sweeteners, nutrients, and flavor enhancers.

8. The application according to any one of claims 1 to 7, characterized in that, The concentration of sennoside A in the drug is not less than 2.24 μM.

9. Application of sennoside A in preparing an ALDH2 enzyme agonist.

10. The application according to claim 9, wherein The concentration of sennoside A in the ALDH2 enzyme agonist is not less than 2.24 μM.

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