Application of piceatannol in preparation of medicine for delaying immune aging

Abstract

The invention discloses an application of piceatannol in delaying immune aging. The application comprises at least one of the following items: an application of piceatannol in preparing a medicine for increasing the number of T lymphocytes; the invention relates to application of piceatannol in preparation of a medicine for enhancing the immune activation ability of T lymphocytes. The invention relates to an application of piceatannol in preparation of a medicine for improving the activity of senescent cells. The piceatannol can act on thymic epithelial cells to promote regeneration of T lymphocytes and improve the immune activation ability of the T lymphocytes to delay immune aging of mice, and finally the purpose of improving the immunity of aged individuals is achieved. The compound can be used for preparing a clinical medicine for delaying immune aging or used as a lead compound of a medicine for improving the immunity of an aged individual.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and particularly relates to the application of piceatannol in the preparation of drugs for delaying immune aging. Background Art

[0002] The elderly are more susceptible to age-related illnesses such as infections, tumors, and autoimmune diseases because their immune systems age with aging. Immune aging manifests itself in the decline of the thymus, a central immune organ, with reduced volume and weight, and increased intrathymic fat production. Furthermore, thymic decline leads to a decrease in the number and function of naive T cells exported from the thymus to the spleen, a peripheral immune organ. This leads to a compensatory increase in peripheral memory T cells, a decrease in the diversity of the TCR repertoire, a decline in immune surveillance and immune clearance, a decrease in T cell-mediated adaptive immune responses, and an increased risk of autoimmune diseases. Therefore, delaying thymic decline has important clinical implications for intervening in immune aging and reducing the incidence of age-related diseases.

[0003] Research has shown that, unlike thymocytes, which reside briefly in the thymus before being released, thymic epithelial cells, which remain permanently in the thymus, play a key role in thymic decline and are considered an important target for delaying thymic decline. Current studies have demonstrated that antioxidant supplementation can activate oxidatively damaged thymic epithelial cells, promoting T lymphocyte regeneration and delaying or preventing immune aging.

[0004] Chinese patent CN118027231A discloses an anti-aging active polysaccharide from E. cochinchinensis, as well as its preparation method and application. The extracted anti-aging active polysaccharide from E. cochinchinensis includes the following monosaccharide components: glucose, xylose, galactose, mannose and arabinose. It can delay the aging of the liver and brain tissue of D-galactose-induced aging mice, and can also activate T lymphocytes and B lymphocytes in the thymus and spleen. It resists aging through immune regulation and has the potential to be used in the preparation of anti-aging or anti-aging pharmaceutical preparations, health products and functional foods.

[0005] Piceatannol (C 14 H 12 Piceatannol (Piceata) is a natural small molecule compound with anti-leukemia activity, primarily extracted from the bark, branches, and leaves of the whitewood fir tree. It inhibits tumor cell proliferation and induces apoptosis by blocking mitosis, making it a promising treatment for a variety of cancers, including ovarian, breast, and non-small cell lung cancer. In recent years, in-depth research on piceatannol has revealed its antioxidant activity, widespread availability, low toxicity, and high economic practicality. However, its role in delaying immune aging remains unclear. Summary of the Invention

[0006] In order to solve the above technical problems, the present application provides an application of piceid in preparing a drug for delaying immune aging, which can increase the number and proportion of T lymphocytes, promote the regeneration of T lymphocytes, and improve the immune activation capacity of T lymphocytes, thereby delaying aging or serving as a lead compound for improving the immunity of aging capsules.

[0007] In order to achieve the above-mentioned purpose, the present application provides an application of piceid in preparing a drug for delaying immune aging, which includes at least one of the following: a: an application of piceid in preparing a drug for increasing the number of T lymphocytes; b: an application of piceid in preparing a drug for enhancing the immune activation capacity of T lymphocytes; c: an application of piceid in preparing a drug for improving the activity of aging cells.

[0008] Preferably, the T lymphocytes are CD3 + T lymphocytes and CD4 + T cells, CD8 + T cells, CD4 + Naive T cells, CD8 + Naive T cells and CD4 + RTE.

[0009] Further preferably, the T lymphocytes are spleen T lymphocytes and / or peripheral blood T lymphocytes.

[0010] Preferably, the aging cells are aging thymic epithelial cells.

[0011] Further preferably, the aging thymic epithelial cells are immortalized thymic epithelial cells transfected with SV40 and then treated with doxorubicin.

[0012] Piceid improves the aging state of thymic epithelial cells induced by doxorubicin.

[0013] More preferably, the treatment condition of doxorubicin is 140-160 ng / mL for 30-40 h.

[0014] Preferably, the concentration of piceid is 10-30 mg / kg.

[0015] Further preferably, the solvent of piceid is a PBS solution containing 1% DMSO.

[0016] Piceid can significantly promote the iTECs cell activity of aging thymic epithelial cells and delay aging.

[0017] Piceid can significantly reduce the β-galactosidase activity of thymic epithelial cells and achieve the effect of delaying aging.

[0018] The piceol reduces the expression level of reactive oxygen species in the thymic epithelial cells, and improves the aging state of the thymic epithelial cells.

[0019] The piceol increases the expression of genes related to T cell development in the aging thymic epithelial cells Kit-L, CD40, Ccl25 and Dll4 genes related to the proliferation of iTECs FgfR2IIIb, SPTL and CyclinE1 genes related to anti-apoptosis Bcl2 and Survivin and promotes the regeneration of T cells.

[0020] The piceol can significantly increase the expression level of autoimmune regulator Aire and the expression level of proliferation factor Ki67 in the thymic epithelial cells.

[0021] Preferably, the core component of the medicine is the piceol and optional pharmaceutically acceptable adjuvants.

[0022] Preferably, the administration route of the medicine is oral administration and parenteral administration, wherein the oral administration includes any one of oral liquid, tablet, pill and capsule; and the parenteral administration includes injection.

[0023] The present application has the following beneficial effects: the present application uses in-vivo and in-vitro experiments, treats the aging thymic epithelial cell model with piceol in-vitro, and treats 17-month-old C57BL / 6J female natural aging mice with piceol by intraperitoneal injection in-vivo. It is proved that the piceol can improve the aging state of the thymic epithelial cells, and can improve the immune aging state of the mice in-vivo, increase the number of mature T lymphocytes and its subgroups in the peripheral immune organs, enhance the immune activation ability, increase the proportion of T lymphocytes in the peripheral blood, and has no obvious liver and kidney toxic side effects. This shows that the piceol can promote the regeneration of T lymphocytes by acting on the thymic epithelial cells, improve the immunity of the aging individuals, and can be used for preparing a clinical medicine for delaying immune aging or as a lead compound of a medicine for improving the immunity of the aging individuals. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 The figure is a schematic diagram of the animal experiment design of the present application.

[0025] Figure 2 The figure is a result graph of the influence of piceol on the thymus index of mice in Example 1.

[0026] Figure 3Figure 3 shows the effect of piceatannol on the number of T lymphocytes and their subsets in mouse spleens; Figure A is a bar graph showing changes in the number of CD3+ T, CD4+ T, and CD8+ T cells, and Figure B is a bar graph showing changes in the number of CD4+ Naïve T, CD4+ RTE, CD8+ Naïve T, and CD8+ RTE cells.

[0027] Figure 4 The results of the effect of piceatannol on the immune activation ability of mouse spleen T lymphocytes in Example 4 are shown in Figure A; Figure A is a histogram of the expression levels of Ki67, IFN-γ, and IL-2, and Figure B is a histogram of the expression levels of Bcl2 in different treatment groups. + The expression level bar graph of T.

[0028] Figure 5 This is a graph showing the effects of piceatannol on the proportions of T cells and their subsets in mouse peripheral blood in Example 5.

[0029] Figure 6 This is a graph showing the effect of piceatannol on the cell viability of senescent thymic epithelial cells in Example 6.

[0030] Figure 7 This is a graph showing the effect of piceatannol on β-galactosidase activity in thymic epithelial cells in Example 7.

[0031] Figure 8 This is a graph showing the effect of piceatannol on the expression level of reactive oxygen species in thymic epithelial cells in Example 8; Figure 9 The effect of piceatannol on T cell development-related genes in aging thymic epithelial cells in Example 9 Kit-L, CD40, Ccl25 and Dll4 , iTECs proliferation-related genes FgfR2IIIb, SPTL and CyclinE1 , anti-apoptosis related genes Bcl2 and Survivin Expression impact results diagram.

[0032] Figure 10 Graphs showing the effects of piceatannol on the expression of the autoimmune regulatory factor Aire and the proliferation factor Ki67 in thymic epithelial cells in Example 10; Figure A is a representative flow cytometry result graph of Aire, B is a histogram of the MFI of Aire, C is a representative flow cytometry result graph of Ki67, and D is a histogram of the MFI of Ki67.

[0033] Figure 11 This is a graph showing the effects of piceatannol and resveratrol on the cell viability of senescent thymic epithelial cells in Example 11. DETAILED DESCRIPTION

[0034] The technical solutions of the present invention are further explained below with reference to the accompanying drawings and specific embodiments. It is worth noting that the following embodiments are only preferred embodiments of the present invention and should not be construed as limiting the present invention. The scope of protection of the present invention shall be determined by the claims. Any modifications or substitutions made to the technical solutions of the present invention by those skilled in the art without creative effort shall fall within the scope of protection of the present invention.

[0035] Cells, animals, and reagents: C57BL / 6J female mice: 17 months old, purchased from Hubei Baiente Company; Piceatannol: purchased from Shanghai Taoshu Biotechnology Co., Ltd., catalog number: T0610; Mouse lymphocyte separation medium: purchased from Tianjin Haoyang Biological Co., Ltd., catalog number: LTS1092PK; Fluorescently labeled antibodies: (see the table below);

[0036] Cell fixation / permeabilization reagents: purchased from BD Biosciences, USA, cat. no. 554714;

[0037] Nuclear antibodies: purchased from (see the table below); iTECs: Immortalized thymic epithelial cells (iTECs) from mice were successfully constructed by Professor Gao Jianli's research group at Zhejiang Chinese Medical University by transfecting primary TECs with SV40. They were kindly donated to our research group for use. Doxorubicin: purchased from MedChemExpress, USA, cat. no. HY-15142A; Example 1 (1) 17-month-old C57BL / 6J female naturally aged mice were treated with different concentrations of piceatannol: Experimental group 1: intraperitoneal injection of 200 μL of 10 mg / kg piceatannol solution every other day; Experimental group 2: intraperitoneal injection of 200 μL of 20 mg / kg piceatannol solution every other day; Experimental group 3: intraperitoneal injection of 200 μL of 30 mg / kg piceatannol solution every other day The solvent used for the piceatannol solution was a PBS solution containing 1% DMSO.

[0038] Control group (DMSO): intraperitoneal injection of 200 μL PBS solution (containing 1% DMSO) every other day (2) At 18 months of age, the mice were sacrificed, and the thymus was taken to measure the size and weight, and the thymus index was calculated, wherein the calculation formula was thymus index (mg / g) = mouse thymus weight (mg) / mouse body weight (g).

[0039] The results are shown in Table 1. Figure 2 As shown in Table 1: compared with the control group (DMSO), the thymus index of the aging mice after intraperitoneal injection of pachyman increased, which indicated that pachyman treatment could delay the thymus atrophy, thymus volume reduction and weight loss caused by increased thymus lipogenesis during the aging process caused by the thymus atrophy caused by the thymus atrophy.

[0040] Example 2 In Example 1, four groups of treated mice were taken, and at 18 months of age, the mouse eyeball blood was taken in a non-anticoagulant tube and left to stand, centrifuged at 3000 rpm for 10 min at 25°C, and the upper serum was aspirated into a 1.5 mL EP tube for detection of liver and kidney function biochemical indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UREA), and creatinine (CREA).

[0041] Table 1: Liver and kidney function indicators of mice under different treatments

[0042] The results are shown in Table 1: there was no significant change in ALT, AST, UREA and CREA in the peripheral blood of each group of mice, which indicated that intraperitoneal injection of 10 mg / kg, 20 mg / kg, 30 mg / kg pachyman had no obvious toxic side effects on aging mice.

[0043] Example 3 (1) In Example 1, four groups of treated mice were taken, and after being sacrificed at 18 months of age, the spleen was taken and placed in a glass dish containing 2 mL of DMEM, and the tail end of the syringe was pressed to release the spleen cells, and the outer membrane of the spleen was discarded, and the spleen lymphocyte suspension was collected into a 5 mL EP tube and centrifuged at 300 g for 5 min, and the supernatant was discarded; (2) 500 μL of red blood cell lysis solution was added and incubated at room temperature for 10 min, 500 μL of PBS was added to terminate the lysis, and the mixture was centrifuged at 300 g for 5 min, and the supernatant was discarded; (3) 4 mL of DMEM was added to resuspend the cell pellet, and 10 μL was taken and added to 190 μL of PBS for counting; (4) 300 μL of the remaining spleen lymphocyte suspension was taken and added to a 96-well plate, and centrifuged at 350 g for 5 min, and the supernatant was discarded; (5) Add fluorescently labeled antibodies including CD3e-PerCP-Cy5.5 (1:100), CD4-APC-Cy7 (1:100), CD8-BV510 (1:100), CD62L-APC (1:100), CD44-BV421 (1:100), CD45RB-PE (1:200), CD16 / 32 FcR (1:100) to each well, and incubate at 4°C for 45 min; (6) After washing with PBS, detect the proportion of each subpopulation of cells by flow cytometry, and then calculate the change in the number of spleen T lymphocytes and each subpopulation of cells in combination with the total number of spleen lymphocytes.

[0044] The results are shown in Table 1. Figure 3 As shown in Table 1, the number of CD3 + T cells, CD4 + T cells, and CD8 + T cells in the spleen increased after treatment with 30 mg / kg of piceid. Meanwhile, the number of CD4 + Naive T cells and CD4 + RTEs in the spleen increased, indicating that piceid can delay immune aging and improve immunity in mice.

[0045] Example 4 (1) Take the four groups of treated mice in Example 1, and take their spleens under sterile conditions after being sacrificed at 18 months of age. Prepare a spleen cell suspension according to steps (1)-(3) of Example 3, and then separate a spleen single cell suspension using mouse lymphocyte separation medium; (2) Add 2×10 6 cells to each well of a 24-well plate, and add the remaining cell suspension to a 96-well plate for flow cytometry detection of the spleen. The detection method is the same as in Example 3; (3) Add 4 μg / mL concanavalin A to each well of a 24-well plate, and incubate at 37°C in a 5% CO2 incubator for 48 h to stimulate lymphocyte proliferation. Meanwhile, add monensin 4 h before collecting the cells.

[0046] (4) Collect the cells into a 96-well plate, and add fluorescently labeled antibodies including CD3e-PerCP-Cy (1:100), CD4-APC-Cy7 (1:100), CD8-BV510 (1:100), and CD16 / 32 FcR (1:100), and incubate at 4°C for 45 min; (5) After washing with PBS, the cells were fixed and permeabilized using a cell fixation / permeabilization reagent, and nuclear antibody Ki67-Alexa Fluor 488 (1:200) and IFNγ-PE (1:100), IL-2-BV421 (1:100), and Bcl2-PE-Cy7 (1:100) were added and incubated at 4°C for 30 min. (6) After washing with PBS, flow cytometry was performed.

[0047] The results are as follows Figure 4 Shown: CD3 in the spleen of mice after treatment with 10 mg / kg and 20 mg / kg piceatannol + The proportion of T cells secreting the pro-inflammatory factor IFN-γ increased, while the proportion of cells secreting IFN-γ decreased significantly after treatment with 30 mg / kg piceatannol. + The proportion of IL-2 secreting T cells increased. At the same time, after treatment with 10 mg / kg piceatannol, CD8 + The proportion of T cells increased. This indicates that piceatannol treatment not only increased the number of T lymphocytes in the spleen of mice, but also enhanced their immune activation capacity. Overall, treating aging mice with 10-20 mg / kg of piceatannol can effectively enhance the immune activation capacity of the organs.

[0048] Example 5 (1) Take the four groups of treated mice in Example 1, collect 50 μL of peripheral blood at 18 months of age into an anticoagulant tube, add 500 μL of red blood cell lysis buffer, lyse at room temperature for 10 min, add 500 μL of PBS to terminate the lysis, centrifuge at 300 g for 5 min, and discard the supernatant; (2) The precipitate was mixed and added to a 96-well plate. Fluorescently labeled antibodies including CD3e-PerCP-Cy (1:100), CD4-APC-Cy7 (1:100), CD8-BV510 (1:100), CD62L-APC (1:100), CD44-BV421 (1:100), and CD16 / 32 FcR (1:100) were added to each well and incubated in the dark at 4°C for 45 min. After washing with PBS, flow cytometry was performed.

[0049] The results are as follows Figure 5 As shown in the figure, after 10 mg / kg piceatannol was treated, the peripheral blood CD3 + T, CD8 + T, CD4 + Naive T、CD8 + The proportion of naive T cells increased. Studies have shown that CD8 +The reduction of naive T cells is considered to be the main sign of immune aging, and the decline of thymus and fatty degeneration are associated with a lower proportion of CD8 + The results showed that the ratio of the above four cell types was related to the proportion of naive T cells, indicating that treating aging mice with piceatannol can delay immune aging. In addition, with the increase of piceatannol concentration, the ratio of the above four cell types gradually decreased, indicating that low-dose piceatannol has a good effect in delaying immune aging, thereby reducing treatment costs and alleviating side effects.

[0050] Example 6 (1) 4000 iTECs were seeded per well of a 96-well plate and divided into 7 groups, with three wells in each group. 2 μL of doxorubicin (150 ng / μL) was added to each well to induce senescence for 36 h. (2) Each group was treated with 0 μM, 0.3 μM, 0.6 μM, 1.2 μM, 2.4 μM, 4.8 μM, and 9.6 μM piceatannol for 72 h, and then the supernatant was discarded; (3) After washing with PBS, 190 μL of DMEM and 10 μL of CCK-8 solution were added to each well and incubated at 37°C for 1 h. The absorbance was read at 450 nm and the cell viability was calculated. The calculation formula is cell viability = [(OD 实验组 -OD 空白组 ) / (OD 对照组 -OD 空白组 )]×100%.

[0051] The results are as follows Figure 6 As shown in the figure, compared with the cells in the 0 μM group, 0.3 μM, 1.2 μM and 4.8 μM piceatannol treatment significantly promoted the viability of senescent iTECs cells, indicating that piceatannol can delay senescence.

[0052] Example 7 (1) 2×10 cells were seeded per well in a 6-well plate. 5 iTECs cells were induced to age by adding 2 μL doxorubicin (150 ng / μL) to the DMSO group and the low, medium, and high concentration PIC treatment groups for 36 h; the Ctrl group (non-senescent group) was treated with 2 μL DMSO for 36 h.

[0053] (2) The cells were treated with 0.3 μM, 1.2 μM, and 4.8 μM piceatannol for 72 h, while the Ctrl and DMSO groups were treated with 2 μL DMSO for 72 h, and then the supernatant was discarded; (3) After washing with PBS, the proportion of senescent cells was detected using a cell senescence β-galactosidase staining kit (purchased from Beyotime, China, catalog number C0602).

[0054] The results are as follows Figure 7 As shown, compared with the Ctrl group without induced senescence, the proportion of senescent iTECs cells increased significantly after 36 h of treatment with doxorubicin, while the proportion of senescent iTECs cells decreased after treatment with 0.3 μM, 1.2 μM and 4.8 μM piceatannol, indicating that piceatannol can reduce the proportion of senescent iTECs, thereby indicating that piceatannol can delay senescence.

[0055] Example 8 (1) Collect cells treated with different concentrations of piceatannol in step (2) of Example 7, add DCFH-DA probe diluted with DMEM medium to a final concentration of 10 μM, and incubate at 37°C in the dark for 30 minutes. Mix by inverting every 3-5 minutes to ensure full contact between the DCFH-DA probe and the cells; (2) The cells were washed three times with DMEM to remove unloaded DCFH-DA probes, and then flow cytometry was used to analyze and quantify the intracellular ROS levels.

[0056] The results are as follows Figure 8 As shown in the data, compared with the Ctrl group, the intracellular ROS content in the DOX group increased, while the reactive oxygen species level in aged iTECs decreased after treatment with 0.3 μM, 1.2 μM and 4.8 μM piceatannol, indicating that piceatannol can reduce the reactive oxygen species level in aged iTECs and improve their cellular senescence state.

[0057] Example 9 (1) 2×10 cells were seeded per well in a 6-well plate. 5 2 μL of doxorubicin (150 ng / μL) was added to each well of iTECs cells and induced to senescence for 36 h; (2) Each group was treated with 0 μM (equal volume of DMSO), 0.3 μM, 1.2 μM, and 4.8 μM piceatannol for 72 h; (3) Discard the culture medium, rinse twice with cold PBS, add 200 μL Trizol to each well, and extract total RNA; (4) Total RNA was reverse transcribed into cDNA using HiScript II Q RT SuperMix for qPCR (+gDNA wiper); (5) Using cDNA as a template, qPCR was performed to detect changes in function-related genes in aging thymic epithelial cells, among which the function-related genes were Bcl2 、 Survivin 、 CCL25 、 Kit-L 、 CD40 、 Ccl25 、 FgfR2IIIb 、Dll4 、 Spt1 、 CyclinE1 The internal reference gene was β-actin, and the primer sequences were shown in Table 2.

[0058] Table 2 qPCR primers

[0059] The results are as follows Figure 9 As shown, compared with the DMSO group, the T cell development-related genes in the piceatannol-treated group Kit-L, CD40, Ccl25 and Dll4、 iTECs proliferation-related genes FgfR2IIIb, SPTL and CyclinE1 , anti-apoptosis related genes Bcl2 and Survivin The expression of thymocytes was increased, indicating that the function of iTECs in nurturing thymocytes was enhanced after piceatannol treatment.

[0060] Example 10 The cells in each treatment group were collected from 6-well plates and fixed and permeabilized for intracellular and nuclear markers using a fixation and permeabilization kit. Nuclear antibodies Ki67-647 (1:200) and Aire-488 (1:100) were added and incubated at 4°C for 30 min. After washing with PBS, flow cytometry analysis was performed.

[0061] The results are Figure 10 Compared with the DMSO group, Aire expression levels increased in senescent iTECs treated with 0.3 μM, 1.2 μM, and 4.8 μM piceatannol, while Ki67 expression increased in senescent iTECs treated with 1.2 μM piceatannol. These results demonstrate that piceatannol can ameliorate doxorubicin-induced iTEC senescence in vitro, enhance its ability to nurture T cell maturation, and promote T cell regeneration.

[0062] Example 11 (1) 4000 iTECs were seeded into each well of a 96-well plate and divided into 8 groups, with 3 wells in each group. 0.2 μL doxorubicin (150 ng / μL) was added to each well and induced to senescence for 36 h. (2) After treatment with 0 μM, 0.3 μM, 1.2 μM, and 4.8 μM piceatannol and 0 μM, 0.3 μM, 1.2 μM, and 4.8 μM resveratrol for 72 h, the supernatant was discarded; (3) After washing with PBS, 190 μL of DMEM and 10 μL of CCK-8 solution were added to each well and incubated at 37°C for 1 h. The absorbance was read at 450 nm. The cell viability was calculated according to the formula [(OD 实验组 -OD 空白组) / (OD 对照组 -OD 空白组 )]×100% to calculate cell viability.

[0063] The results are Figure 11 It can be seen that compared with 4.8 μM resveratrol, 4.8 μM piceatannol can better increase the cell viability of senescent thymic epithelial cells after 72 h of treatment.

Claims

1. The use of piceatannol in the preparation of a drug for delaying immune aging, characterized in that: The application includes at least one of the following: a: Use of piceatannol in the preparation of a drug for increasing the number of T lymphocytes; b: Application of piceatannol in the preparation of drugs for enhancing the immune activation ability of T lymphocytes; c: Application of piceatannol in the preparation of drugs for improving the vitality of senescent cells.

2. The use according to claim 1, wherein: The T lymphocytes are CD3 + T lymphocytes and their subsets CD4 + T cells, CD8 + T cells, CD4 + Naive T cells, CD8 + Naive T cells and CD4 + One or more of RTE.

3. The use according to claim 2, characterized in that: The T lymphocytes are spleen T lymphocytes and / or peripheral blood T lymphocytes.

4. The use according to claim 1, characterized in that: The senescent cells are senescent thymic epithelial cells.

5. The use according to claim 4, characterized in that: Piceatannol improves doxorubicin-induced senescence of thymic epithelial cells.

6. The use according to claim 4, characterized in that: The doxorubicin treatment condition is 140-160 ng / mL for 30-40 hours.

7. The use according to claim 1, characterized in that: The effective concentration of piceatannol is 10-30 mg / kg.

8. The use according to claim 7, characterized in that: The solvent of the piceatannol is a PBS solution containing 1% DMSO.

9. The use according to claim 1, characterized in that: The core component of the drug is composed of the piceatannol according to claim 1 and optional pharmaceutically acceptable adjuvants.

10. The use according to claim 1, characterized in that: The administration routes of the drug are oral administration and parenteral administration, wherein oral administration includes any one of oral solution, tablets, pills and capsules; and parenteral administration includes injection.

Images