Application of sulforaphane in preparation of medicine for treating vascular endothelial impairment

Abstract

The invention discloses application of sulforaphane in preparation of a medicine for treating vascular endothelial impairment, and relates to the technical field of medicines. In-vitro cell experiments prove that the sulforaphane can effectively relieve inflammatory response and activation state of endothelial cells by inhibiting expression of classical adhesion molecules such as SELE, VCAM1 and ICAM1 and various chemotactic factors, so that TNF-alpha induced monocyte adhesion is inhibited; besides, the sulforaphane enhances the anti-oxidation defense capability of endothelial cells by activating an Nrf2 signal channel, effectively relieves oxidative stress injury and plays a role in protecting endothelium; animal experiments further prove that in an atherosclerosis and hypertension mouse model, the sulforaphane down-regulates the expression of adhesion molecules in endothelial cells and up-regulates the expression of antioxidant proteins and vasodilatation promoting proteins at the same time, so that the obvious anti-atherosclerosis and antihypertensive effects are achieved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to drugs for treating vascular endothelial damage, and more specifically to the application of sulforaphane in the preparation of drugs for treating vascular endothelial damage. Background Technology

[0002] As the core regulatory unit of the cardiovascular system, the vascular endothelium plays a crucial role in the development and progression of cardiovascular diseases. Its dysfunction is both the initial stage of diseases such as atherosclerosis, hypertension, and heart failure, and a significant pathological mechanism driving disease progression. Under physiological conditions, the vascular endothelium maintains vascular tone homeostasis and inhibits platelet activation and inflammatory responses by precisely regulating the dynamic balance between vasodilators such as nitric oxide (NO) and prostacyclin (PGI2) and vasoconstrictors such as endothelin-1 (ET-1) and angiotensin II. However, under pathological conditions, impaired endothelial function leads to a significant decrease in NO bioavailability, with pro-inflammatory and procoagulant mechanisms becoming dominant. This results in vasomotor dysfunction, inflammatory cell infiltration, and abnormal lipid deposition, thereby accelerating the progression of atherosclerosis. During this process, endothelial cells overexpress vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), and E-selectin (SELE), among other adhesion molecules, mediating monocyte adhesion and promoting their differentiation into macrophages. Macrophages then transform into foam cells by phagocytizing oxidized low-density lipoprotein (ox-LDL) or acetylated low-density lipoprotein (ac-LDL), forming the core pathological component of atherosclerotic plaques. Simultaneously, the abnormal secretion of von Willebrand factor (vWF) and tissue factor (TF) by endothelial cells further promotes platelet activation and thrombus formation, significantly increasing the risk of acute coronary syndrome. In the course of hypertension, endothelium-dependent vasomotor dysfunction leads to vascular remodeling and insufficient end-organ perfusion; while diabetes exacerbates endothelial damage through oxidative stress and advanced glycation end products (AGEs), inducing diabetic microvascular complications. More importantly, impaired endothelial repair capacity also hinders the establishment of collateral circulation, exacerbating myocardial ischemia. Although current conventional drug treatments for coronary heart disease (including antiplatelet therapy, lipid-lowering therapy, anti-ischemic therapy, anti-heart failure therapy, and integrated traditional Chinese and Western medicine treatments) have achieved significant efficacy, there is still a lack of specific interventions targeting endothelial function. Therefore, developing novel treatment strategies that target the protection of endothelial function (such as targeted anti-inflammatory therapy, precise antioxidant therapy, and selective inhibition of monocyte adhesion) has important clinical value for improving the comprehensive treatment system for coronary heart disease.

[0003] Sulforaphane (SFN, molecular formula C6H) 11S2NO (relative molecular mass 177.29) is a naturally occurring isothiocyanate compound with important biological activity, mainly derived from cruciferous vegetables such as broccoli, cauliflower, cabbage, and kale, especially abundant in broccoli sprouts. It is the main active product generated by the hydrolysis of glucosinolate / sulforaphane under the action of myrosinase. The most significant characteristic of sulforaphane lies in its multi-target biological effects: on the one hand, by activating the Nrf2 / ARE signaling pathway, it upregulates the expression of phase II detoxification enzymes such as heme oxygenase-1 (HO-1) and glutathione peroxidase (GPx), significantly enhancing the cellular oxidative stress defense capacity; on the other hand, by inhibiting the activation of key inflammatory signaling pathways such as NF-κB, it effectively regulates the production and release of pro-inflammatory cytokines. Existing studies have confirmed that sulforaphane exhibits unique pharmacological value in areas such as tumor chemoprevention, immunomodulation, neuroprotection, and intervention in metabolic diseases. However, it is worth noting that there are still significant gaps in the study of its mechanism of action in the field of vascular endothelial protection, especially the systemic effects on the transcriptional regulatory network of vascular endothelial cells at the whole genome level have not been fully elucidated. This greatly limits the in-depth understanding of the cardiovascular protective effect of this compound and its clinical application development. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides the application of sulforaphane in the preparation of drugs for treating vascular endothelial damage.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows:

[0006] This invention provides the application of sulforaphane in the preparation of drugs for treating vascular endothelial damage.

[0007] Preferably, the sulforaphane is used to prepare a drug for treating diseases related to damage to the vascular endothelium.

[0008] Preferably, the vascular endothelial damage-related diseases include cardiovascular and cerebrovascular diseases and metabolic diseases.

[0009] Preferably, the cardiovascular and cerebrovascular disease is at least one of coronary atherosclerotic heart disease (coronary heart disease), hypertension, stroke, or heart failure.

[0010] It should be noted that sulforaphane exerts a significant antihypertensive effect through multiple mechanisms, including synergistic regulation of vasodilation, reduction of oxidative stress damage, and inhibition of inflammatory responses; sulforaphane also exerts its anti-atherosclerotic effect by inhibiting the expression of endothelial cell adhesion molecules. Furthermore, sulforaphane glycosides are converted into sulforaphane in the body.

[0011] Preferably, the metabolic disease includes at least one of type 2 diabetes, non-alcoholic fatty liver disease, or obesity.

[0012] Preferably, the drug is a drug that alleviates the activated state of endothelial cells by inhibiting the expression of endothelial cell adhesion molecules, including but not limited to SELE, VCAM1, and ICAM1.

[0013] Preferably, the drug is a drug that inhibits the inflammatory response of endothelial cells by inhibiting the expression of endothelial cell chemokines, wherein the chemokines include, but are not limited to, CCL2, CX3CL1, CXCL2 and CXCL6.

[0014] Preferably, the drug is a drug that protects damaged endothelial cells by upregulating the expression levels of antioxidant and / or anti-inflammatory related genes in endothelial cells, wherein the antioxidant factors include, but are not limited to, HMOX1, NQO1, SRXN1 and TXNRD1, and the anti-inflammatory factors include, but are not limited to, SOCS3, DUSP1 and APLN.

[0015] Preferably, the drug is a drug that enhances the antioxidant defense capacity of endothelial cells by activating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway.

[0016] Preferably, the drug is a drug that can effectively block endothelial cell activation and its mediated mononuclear cell adhesion cascade.

[0017] Preferably, the drug comprises sulforaphane and / or sulforaphane glycosides, and / or extracts containing sulforaphane glycosides.

[0018] Preferably, the drug further includes pharmaceutically acceptable excipients.

[0019] Preferably, the dosage form of the drug is selected from at least one of tablets, capsules, granules, pills, injections, suspensions, dispersants, syrups, sprays, and ointments.

[0020] Compared with existing technologies, the beneficial effects of this solution are:

[0021] This invention demonstrates through in vitro cell experiments that sulforaphane can effectively reduce the inflammatory response and activation state of endothelial cells by inhibiting the expression of classical adhesion molecules such as E-selectin (SELE), vascular cell adhesion molecule-1 (VCAM1), and intercellular adhesion molecule-1 (ICAM1), as well as various chemokines, thereby inhibiting tumor necrosis factor-α (TNF-α)-induced monocyte adhesion. Furthermore, sulforaphane enhances the antioxidant defense capacity of endothelial cells by activating the Nrf2 signaling pathway, effectively reducing oxidative stress damage and exerting an endothelial protective effect. Animal experiments further confirm that in mouse models of atherosclerosis and hypertension, sulforaphane downregulates the expression of adhesion molecules in endothelial cells while upregulating the expression of antioxidant proteins and pro-vasodilatory proteins, thus exerting significant anti-atherosclerotic and antihypertensive effects. Attached Figure Description

[0022] Figure 1 Transcriptome sequencing of human umbilical vein endothelial cells (HUVEC) (A is a differential gene volcano plot, where blue dots represent genes downregulated after sulforaphane (SFN) intervention, purple-red dots represent genes upregulated after SFN intervention, and gray dots represent genes unchanged after SFN intervention; B is a differential gene heatmap).

[0023] Figure 2 The effect of sulforaphane on the expression of classical adhesion molecules SELE, VCAM1, and ICAM1 in endothelial cells (AC represent the quantitative analysis of mRNA expression levels of SELE, VCAM1, and ICAM1, respectively; D and E represent the immunoblot representation and quantitative analysis of SELE, VCAM1, and ICAM1 protein expression, respectively; statistical figures represent mean ± standard deviation, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; Tubulin is the internal reference protein).

[0024] Figure 3 The effects of sulforaphane on the expression of chemokines CCL2, CX3CL1, CXCL2 and CXCL6 are shown in Figure A (Quantitative analysis of CCL2 mRNA expression level, Figure B (Quantitative analysis of CX3CL1 mRNA expression level, Figure C (Quantitative analysis of CXCL2 mRNA expression level), Figure D (Quantitative analysis of CXCL6 mRNA expression level)).

[0025] Figure 4 The effects of sulforaphane on the expression of antioxidant and anti-inflammatory factors (A is the quantitative analysis diagram of HMOX1 mRNA expression level, B is the quantitative analysis diagram of NQO1 mRNA expression level, C is the quantitative analysis diagram of SOCS3 mRNA expression level, and D is the quantitative analysis diagram of DUSP1 mRNA expression level).

[0026] Figure 5 The effect of sulforaphane on the expression of transcription factor Nrf2 and downstream antioxidant proteins (A and B are representative immunoblot images and quantitative analysis images of Nrf2 expression in extracted nuclear proteins, respectively; C and D are representative immunoblot images and quantitative analysis images of antioxidant proteins HO-1 and NQO1, respectively).

[0027] Figure 6 To detect the effect of sulforaphane on monocyte adhesion in an endothelial cell-monocyte adhesion assay (A is a confocal microscopy image of THP-1 monocytes, with purple dots representing monocytes; B is a statistical graph of the number of THP-1 monocytes observed in each field of view).

[0028] Figure 7 The effect of feeding broccoli seed water extract on atherosclerosis in mice (A and B are gross Oil Red O staining and quantitative analysis of the aorta, with red representing atherosclerotic plaques; C and D are HE staining and quantitative analysis of aortic root sections, with the dashed box representing atherosclerotic plaques).

[0029] Figure 8 The effect of feeding broccoli seed water extract on the expression of adhesion molecules SELE, VCAM1 and ICAM1 in atherosclerotic plaques (A and B are Western Blot images of the protein levels and quantitative analysis of SELE, VCAM1 and ICAM1 in vascular endothelial cells obtained by magnetic bead sorting, respectively; C and D are immunohistochemical images and quantitative analysis images of SELE in plaques, respectively).

[0030] Figure 9 The effect of feeding broccoli seed water extract on macrophage infiltration in atherosclerotic plaques (A and B are representative immunofluorescence images and quantitative analysis images of CD68, a macrophage-specific marker in plaques, respectively).

[0031] Figure 10 The effects of feeding broccoli seed water extract on blood pressure and endothelial function-related proteins in hypertensive model mice (A is diastolic blood pressure in mice, B is systolic blood pressure in mice; C and D are Western blotting results showing the protein levels and quantitative analysis of eNOS, HO-1, NOX2, and ICAM1 in vascular endothelial cells obtained by magnetic bead sorting). Detailed Implementation

[0032] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0033] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0034] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0035] The experimental methods used in the following embodiments are as follows:

[0036] I. Experimental Materials

[0037] TNF-α was purchased from R&D Systems (product number: #410-MT), sulforaphane was purchased from Sigma-Aldrich (product number: S6317; purity: ≥95%; oil), broccoli seed water extract (containing 20% ​​sulforaphane precursor sulforaphane glycoside, purchased from Ganzhou Huahan Biotechnology Co., Ltd.), and Ang II was purchased from MCE (product number: HY-13948; purity: 99.98%).

[0038] II. Experimental Methods

[0039] (1) In vitro cell experiments

[0040] Cell Culture and Processing: Human umbilical vein endothelial cells (HUVECs) were cultured in complete ECM medium containing 20% ​​fetal bovine serum (FBS), 1% penicillin / streptomycin, and endothelial growth factor at 37°C in a 5% CO2 incubator. The medium was changed every 2 days. When the cells reached 80%–90% confluence, they were passaged using 0.25% trypsin (P3–P8 passages were used for experiments). Before the experiment, cells were seeded in 6-well plates (density 1 × 10⁶ cells / well). 5 Cells / well were cultured overnight and then synchronized with serum-free medium for 12 h to eliminate serum interference. The experiment was divided into four groups: ① Control group (NC group): normal culture without intervention; ② TNF-α group: stimulation with 10 ng / mL TNF-α (diluted with PBS or serum-free medium) for 24 h; ③ SFN+TNF-α group: pretreatment with 1 μM sulforaphane (SFN, final concentration ≤ 0.1%) for 2 h, followed by co-incubation with TNF-α (10 ng / mL) for 24 h; ④ SFN control group (optional): stimulation with only 1 μM SFN for 24 h. Each group had 3–6 replicates, and each experiment was repeated 3 times.

[0041] (2) In vivo animal experiments

[0042] Establishment of a mouse model of atherosclerosis: An atherosclerosis model was established using ApoE- / - mice, which were divided into a control group (fed a high-fat, high-cholesterol diet) and an SFN group (fed a high-fat, high-cholesterol diet supplemented with broccoli seed aqueous extract). Broccoli seed aqueous extract contains 20% sulforaphane, which is converted into bioactive SFN in the animals.

[0043] Establishment of a mouse hypertension model: A mouse hypertension model was established by continuous infusion of angiotensin II (Ang II, 500 ng / kg / min, for 28 days) via a subcutaneously implanted micro-osmotic pump. The mice were divided into a control group (fed a normal maintenance diet) and an SFN group (fed a normal maintenance diet supplemented with broccoli seed water extract).

[0044] Example 1: Study on the regulatory role of SFN on endothelial cell gene expression profile based on transcriptome sequencing

[0045] This embodiment uses whole transcriptome sequencing technology to compare and analyze the gene expression profiles of endothelial cells in the TNF-α group and the SFN+TNF-α group. For example... Figure 1 As shown, SFN intervention can significantly alter the gene expression profile of endothelial cells (screening criteria: |log2FC|≥1 and p<0.05), identifying a total of 1035 differentially expressed genes (DEGs), of which 305 genes were upregulated and 730 genes were downregulated.

[0046] (1) Analysis of downregulated gene function

[0047] SFN treatment significantly suppressed the expression of key genes associated with monocyte recruitment and adhesion:

[0048] ① Adhesion molecule family: including E-selectin (SELE / CD62E), vascular cell adhesion molecule-1 (VCAM1), and intercellular adhesion molecule-1 (ICAM1).

[0049] ② Chemokines family: monocyte chemoattractant protein-1 (CCL2 / MCP-1), chemokine C-X3-C-monotone ligand 1 (CX3CL1), and CXCL2, CXCL6, etc.

[0050] (2) Analysis of upregulated gene function

[0051] SFN treatment significantly activated the following endothelial cell protective pathways:

[0052] ① Antioxidant defense system: Heme oxygenase-1 (HMOX1), NAD(P)H quinone oxidoreductase 1 (NQO1), thioredoxin reductase 1 (TXNRD1), etc.;

[0053] ② Anti-inflammatory regulatory network: Cytokine signaling inhibitory factor 3 (SOCS3), dual specific phosphatase 1 / 4 (DUSP1 / 4), pentameric protein 3 (PTX3), growth differentiation factor 15 (GDF15), etc.;

[0054] ③ Cell protection and anti-apoptosis pathways: BCL2 / adenovirus E1B interacting protein 3-like (BNIP3L), zinc finger protein MAT3 (ZMAT3), etc.

[0055] In summary, transcriptomic data confirm that SFN synergistically regulates endothelial cell function through multiple targets and pathways. Its core mechanisms include: significantly enhancing endothelial cell antioxidant defense capabilities by upregulating the expression of antioxidant genes such as HMOX1 and NQO1; significantly downregulating the expression of various adhesion molecules and chemokines to inhibit endothelial cell inflammation and activation; and enhancing endothelial cell survival by regulating the expression of anti-apoptotic genes such as BNIP3L and ZMAT3. This multi-target, multi-level comprehensive regulatory characteristic gives SFN a unique vascular protective effect, providing a new potential therapeutic target for the prevention and treatment of cardiovascular diseases such as atherosclerosis, and possessing significant clinical translational value.

[0056] Example 2: Effect of SFN on TNF-α-induced expression of endothelial cell adhesion molecules

[0057] In this embodiment, qRT-PCR and Western Blot techniques were used to detect the mRNA and protein expression levels of key adhesion molecules (SELE, VCAM1, and ICAM1) in endothelial cells of normal control group (NC group), TNF-α stimulation group (TNF-α group), and SFN intervention group (SFN+TNF-α group). Figure 2 Experimental results showed that TNF-α stimulation significantly induced the upregulation of expression of endothelial cell activation markers SELE, VCAM1, and ICAM1 (p<0.0001), while SFN pretreatment significantly inhibited this effect. Specifically, SELE mRNA levels decreased by 96% (p<0.0001) and protein levels by 98% (p<0.0001); VCAM1 mRNA levels decreased by 95% (p<0.0001) and protein levels by 97% (p<0.0001); and ICAM1 mRNA levels decreased by 92% (p<0.0001) and protein levels by 98% (p<0.005). These results confirm at both the gene and protein levels that SFN can effectively inhibit TNF-α-induced endothelial cell activation, and its molecular mechanism may be achieved by inhibiting the expression of key adhesion molecules such as SELE, VCAM1, and ICAM1.

[0058] Example 3: Effects of SFN on TNF-α-induced endothelial cell chemokines

[0059] This embodiment used qRT-PCR to detect changes in the mRNA expression levels of key chemokines in endothelial cells of the normal control group (NC group), the TNF-α stimulation group (TNF-α group), and the SFN intervention group (SFN+TNF-α group). Figure 3 As shown, TNF-α stimulation significantly upregulated the expression of multiple chemokines (p<0.0001), while SFN pretreatment effectively inhibited this pro-inflammatory effect, specifically: CCL2 expression decreased by 66% (p<0.0001), CX3CL1 by 84% (p<0.0001), CXCL2 expression decreased by 82% (p<0.0001), and CXCL6 expression decreased by 77% (p<0.0001). These results suggest that SFN may inhibit the inflammatory response of endothelial cells by regulating the expression of multiple chemokines.

[0060] Example 4: Effects of SFN on the antioxidant defense capacity of endothelial cells

[0061] This embodiment used qRT-PCR to detect changes in the expression levels of antioxidant and anti-inflammatory genes in endothelial cells of the normal control group (NC group), the TNF-α stimulation group (TNF-α group), and the SFN intervention group (SFN+TNF-α group). Figure 4 The results showed that SFN treatment significantly upregulated the expression levels of antioxidant and anti-inflammatory genes in endothelial cells. Specifically, the mRNA expression of antioxidants HMOX1 and NQO1 increased by 94% (p<0.0001) and 86% (p<0.0001), respectively; simultaneously, the mRNA expression of anti-inflammatory factors SOCS3 and DUSP1 increased by 90% (p<0.0001) and 85% (p<0.0001), respectively. These results indicate that SFN exerts an endothelial protective effect by activating the antioxidant defense system of endothelial cells and inhibiting the inflammatory response.

[0062] The protein levels of antioxidant factors in four groups of endothelial cells (NC group, SFN group, TNF-α group and SFN+TNF-α group) were further detected by Western blotting. Figure 5 The results showed that SFN treatment significantly activated the antioxidant defense system of endothelial cells. On the one hand, it promoted the nuclear translocation of the core transcriptional regulator Nrf2 (p<0.0001), indicating enhanced transcriptional activity. On the other hand, it significantly upregulated the expression levels of downstream target genes of Nrf2, with HMOX1 increasing by 83% (p<0.0001) and NQO1 increasing by 60% (p=0.0002). These results confirm at the protein level that SFN enhances the antioxidant defense capacity of endothelial cells by activating the Nrf2 signaling pathway.

[0063] Example 5: Effects of SFN on TNF-α-induced endothelial cell activation and monocyte adhesion.

[0064] In this study, endothelial cells from the normal control group (NC group), the TNF-α stimulation group (TNF-α group), and the SFN intervention group (SFN+TNF-α group) were co-incubated with THP-1 monocytes for 30 minutes to perform a monocyte-endothelial cell adhesion experiment. Immunofluorescence results showed that TNF-α stimulation significantly enhanced monocyte adhesion, while SFN pretreatment effectively inhibited this effect, reducing the number of adherent cells by 67.3±5.2% (p<0.0001). This result confirms that SFN can significantly block TNF-α-induced endothelial cell activation and its mediated monocyte adhesion cascade (see...). Figure 6 ).

[0065] Example 6

[0066] This example compares plaque development in the control group (NC group) and the SFN treatment group (SFN group) after 12 weeks of feeding. Gross Oil Red O staining of the aorta and HE staining of paraffin sections from the aortic root showed a significant reduction in plaque area in the SFN treatment group, with a 24% decrease in aortic plaque area (p=0.0103) and a 26% decrease in aortic root plaque area (p=0.0098) (see...). Figure 7 After separating vascular endothelial cells using magnetic bead sorting technology, Western blot analysis showed that SFN treatment significantly downregulated the expression levels of adhesion molecules in endothelial cells, specifically ICAM1 by 70% (p=0.0003), VCAM1 by 55% (p=0.0001), and SELE by 73% (p<0.0001) (see [link to article]). Figure 8 Immunohistochemical staining further confirmed that the expression level of SELE in epithelial cells within the plaque area of ​​the SFN treatment group was significantly reduced (decreased by 27%, p=0.001) (see [link to relevant documentation]). Figure 8 Simultaneously, immunofluorescence staining confirmed that SFN effectively reduced mononuclear / macrophage infiltration within plaques (a decrease of 64%, p<0.0001) (see [link to relevant documentation]). Figure 9 These results confirm, at the animal level, that SFN exerts its anti-atherosclerotic effect by inhibiting the expression of endothelial cell adhesion molecules.

[0067] Example 7

[0068] This study compared the blood pressure of the control group (NC group) and the SFN treatment group (SFN group) after 4 weeks of feeding. Non-invasive tail cuff blood pressure monitoring showed that, compared with the NC group, the SFN group mice exhibited a 12% decrease in systolic blood pressure (p=0.0099) and a 10.1% decrease in diastolic blood pressure (p=0.0211). Western blotting analysis using magnetic bead sorting to separate vascular endothelial cells showed that SFN treatment significantly upregulated the expression levels of endothelial nitric oxide synthase (eNOS), which maintains vasodilation, and heme oxygenase-1 (HO-1), a key molecule for antioxidative stress (70% and 71%, respectively, p<0.0001), while significantly downregulating the expression of pro-oxidative stress molecules NADPH oxidase-2 (NOX2) and the pro-inflammatory factor ICAM-1 (61% and 70%, respectively, p<0.0001) (see [link to relevant documentation]). Figure 10 These results strongly suggest that sulforaphane may exert its antihypertensive effect through multiple mechanisms, including synergistic regulation of vasodilation, reduction of oxidative stress damage, and inhibition of inflammatory responses.

[0069] The above specific embodiments are merely explanations of the present invention and are not intended to limit the present invention. After reading this specification, those skilled in the art can make modifications to these embodiments without contributing any inventive step, but as long as they are within the scope of the claims of the present invention, they are protected by patent law.

Claims

1. Application of sulforaphane in the preparation of drugs for treating vascular endothelial damage.

2. The application according to claim 1, characterized in that, The sulforaphane is used to prepare drugs for treating diseases related to vascular endothelial damage.

3. The application according to claim 2, characterized in that, The diseases related to damage to the vascular endothelium include cardiovascular and cerebrovascular diseases and metabolic diseases.

4. The application according to claim 3, characterized in that, The cardiovascular and cerebrovascular diseases mentioned are at least one of coronary atherosclerotic heart disease, hypertension, stroke, or heart failure.

5. The application according to claim 3, characterized in that, The metabolic disease is at least one of type 2 diabetes, non-alcoholic fatty liver disease, or obesity.

6. The application according to claim 1, characterized in that, The drug is a drug that reduces the activated state of endothelial cells by inhibiting the expression of endothelial cell adhesion molecules, including but not limited to SELE, VCAM1 and ICAM1.

7. The application according to claim 1, characterized in that, The drug is a drug that inhibits the inflammatory response of endothelial cells by inhibiting the expression of endothelial cell chemokines, including but not limited to CCL2, CX3CL1, CXCL2 and CXCL6.

8. The application according to claim 1, characterized in that, The drug is a drug that protects endothelial cells by upregulating the expression levels of antioxidant and / or anti-inflammatory related genes in endothelial cells. The antioxidant factors include, but are not limited to, HMOX1, NQO1, SRXN1, and TXNRD1, and the anti-inflammatory factors include, but are not limited to, SOCS3, DUSP1, and APLN.

9. The application according to claim 1, characterized in that, The drug is one that enhances the antioxidant defense capacity of endothelial cells by activating the Nrf2 signaling pathway.

10. The application according to claim 1, characterized in that, The drug is one that can effectively block endothelial cell activation and the monocyte adhesion cascade it mediates.

11. The application according to claim 1, characterized in that, The drug includes sulforaphane and / or sulforaphane glycosides, and / or extracts containing sulforaphane glycosides.

12. The application according to claim 1, characterized in that, The drug also includes pharmaceutically acceptable excipients.

13. The application according to claim 1, characterized in that, The dosage form of the drug is selected from at least one of tablets, capsules, granules, pills, injections, suspensions, dispersants, syrups, sprays, and ointments.

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