Application of sesamoside in medicine with neuroprotective effect on Parkinson's disease

Abstract

The invention belongs to the technical field of medicines, and particularly discloses application of sesamoside in a medicine with a neuroprotective effect on Parkinson's disease, which is specifically characterized in that alpha-Syn plasmids are transfected into mouse dopaminergic neuron MES23.5 cells to establish an alpha-Syn overexpressed PD cell model, and PD cells are intervened by adding the sesamoside. Results prove that the sesamoside can improve cell viability and reduce cytotoxicity by reducing mitochondrial damage of PD cells, and has a neuroprotective effect on PD damaged neurons; a PD mouse model is established by utilizing MPTP intraperitoneal injection, intervention is carried out through sesamoside intragastric administration, and a result proves that sesamoside can effectively improve the athletic ability of a PD mouse. The results show that the sesamoside can effectively play a neuroprotective role on PD and has a good clinical application prospect.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to the application of flaxseed glycosides in drugs with neuroprotective effects on Parkinson's disease. Background Art

[0002] The core pathological features of Parkinson's disease (PD) include the loss of dopaminergic neurons in the substantia nigra of the midbrain: this is one of the main pathological features of PD, causing patients to experience motor dysfunction such as tremor, rigidity and bradykinesia; Lewy body formation: the appearance of Lewy bodies formed by abnormal aggregation of α-synuclein (α-Syn) in the remaining neurons is another hallmark pathological change of PD. Traditional PD animal models mainly use various neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone, to cause selective damage to dopaminergic neurons. This type of animal model well simulates the substantia nigra dopaminergic neuron damage and motor symptoms of PD. The specific role of α-Syn in PD is as follows: (1) Abnormal aggregation of α-Syn: Abnormal increase and aggregation of α-Syn is one of the key factors in the onset of PD. It may lead to mitochondrial dysfunction and then induce neuronal damage. (2) Mitochondrial dysfunction: α-Syn can exist in mitochondria, inhibit the activity of mitochondrial complex I, lead to a decrease in mitochondrial membrane potential (MMP), and ultimately cause mitochondrial dysfunction and neuronal death. The role of mitochondria in PD: (1) The importance of mitochondrial function: Mitochondria are the energy factories of cells, mainly responsible for generating ATP and maintaining the normal physiological functions of cells. It also participates in processes such as apoptosis and autophagy, and is essential for cell growth and survival. (2) The role of MMP: MMP is an important indicator of normal mitochondrial function, and its stability is a prerequisite for maintaining mitochondrial oxidative phosphorylation and ATP generation. The decrease in MMP is closely related to pathological processes such as apoptosis and necrosis. The effect of α-Syn on mitochondria: α-Syn may exist in the form of small polymers, inducing mitochondrial fragmentation and destroying its morphology. This damage can lead to mitochondrial dysfunction and further aggravate neuronal damage.

[0003] Current studies have revealed the association between mitochondrial dysfunction and typical pathological manifestations of PD, but the specific molecular mechanism still needs further exploration. The pathogenesis of PD is complex and involves multiple pathological processes. In-depth research on the relationship between mitochondrial dysfunction and pathological changes and clinical symptoms will help develop more effective diagnostic and treatment methods and improve the quality of life of PD patients.

[0004] Sesamoside is a terpene isolated from Lamiophlomis rotata Kudo. The research results show that Sesamoside has antioxidant and anti-glycation effects. Sesamoside interacts with multiple targets related to glycolipid metabolism, nucleotide metabolism, and inflammation. Sesamoside exerts an anti-hypoxic effect through AKR1B1. In addition, Sesamoside can alleviate paclitaxel-induced neuropathic pain. However, so far, there is no relevant research on whether Sesamoside has a protective effect on PD nerve damage. We propose a hypothesis that Sesamoside can reduce cell damage of PD dopaminergic neurons and improve the motor ability of PD model mice by inhibiting mitochondrial damage. Summary of the Invention

[0005] The object of the present invention is to provide an application of sesamoside in a drug for neuroprotection of Parkinson's disease. Specifically, sesamoside reduces the cell damage and cytotoxicity of dopaminergic neuron MES23.5 cells induced by overexpressed α-Syn protein, improves the mitochondrial dysfunction caused by overexpressed α-Syn protein in dopaminergic neuron MES23.5, alleviates the motor disorder of Parkinson's disease mice, and thus plays a protective role in Parkinson's disease nerve damage.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] One object of the present invention is to provide an application of sesamoside in a drug for neuroprotection of Parkinson's disease.

[0008] Further explanation, the sesamoside plays a protective role in neuron damage.

[0009] Further explanation, the sesamoside reduces the cell damage and cytotoxicity of dopaminergic neuron MES23.5 cells induced by overexpressed α-Syn protein, improves the mitochondrial dysfunction caused by overexpressed α-Syn protein in dopaminergic neuron MES23.5, alleviates the motor disorder of Parkinson's disease mice, and thus plays a protective role in Parkinson's disease nerve damage.

[0010] Another object of the present invention is to provide a drug for neuroprotection of Parkinson's disease, and the main component of the drug is sesamoside.

[0011] Further explanation, the effective concentration of the sesamoside for reducing the cell damage and cytotoxicity of dopaminergic neuron MES23.5 cells induced by overexpressed α-Syn protein in vitro is 25 μM - 100 μM.

[0012] Further illustration, the effective concentration of the vicianin for improving the motor ability of the PD model mice induced by MPTP in vivo is 5 mg / kg - 10 mg / kg.

[0013] Further illustration, the drug is prepared into a clinically acceptable pharmaceutical preparation with vicianin as the main component, plus pharmaceutically acceptable excipients or auxiliary components.

[0014] Further illustration, the pharmaceutical preparation of the drug includes any one of tablets, pills, capsules, granules, syrups, powders, powders for external use, suppositories, drops, emulsions, solutions, suspensions.

[0015] The third object of the present invention is to provide a pharmaceutical composition for treating and / or preventing Parkinson's disease, and the pharmaceutical composition is prepared into a clinically acceptable pharmaceutical preparation with vicianin as the main component, plus pharmaceutically acceptable excipients or auxiliary components.

[0016] Further illustration, the content of the vicianin in the pharmaceutical composition is 5 mg / kg - 10 mg / kg.

[0017] Further illustration, the pharmaceutical preparation of the drug includes any one of tablets, pills, capsules, granules, syrups, powders, powders for external use, suppositories, drops, emulsions, solutions, suspensions.

[0018] Generally speaking, as a drug, it is usually clinically applied after being prepared into a preparation. The pharmaceutical composition of the present invention can be prepared according to the methods well-known in the art. It can be combined with one or more pharmaceutically acceptable solid or liquid excipients and / or adjuvants to form any dosage form suitable for human or animal use.

[0019] The pharmaceutical composition of the present invention or the pharmaceutical composition containing it can be administered in unit dosage form, and the administration route can be enteral or parenteral, such as oral administration, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum, etc.

[0020] The dosage form for administration can be a liquid dosage form, a solid dosage form or a semi-solid dosage form. The liquid dosage form can be a solution (including true solution and colloidal solution), an emulsion (including o / w type, w / o type and multiple emulsion), a suspension, an injection (including aqueous injection, powder injection and infusion), an eye drop, a nasal drop, a lotion and a liniment, etc.; the solid dosage form can be a tablet (including ordinary tablet, enteric-coated tablet, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, orally disintegrating tablet), a capsule (including hard capsule, soft capsule, enteric-coated capsule), a granule, a powder, a pellet, a dropping pill, a suppository, a film, a patch, an aerosol, a spray, etc.; the semi-solid dosage form can be an ointment, a gel, a paste, etc.

[0021] The pharmaceutical composition of the present invention can be formulated into conventional preparations, sustained-release preparations, controlled-release preparations, targeted preparations and various particulate drug delivery systems. In order to formulate the pharmaceutical composition of the present invention into tablets, various excipients well-known in the art can be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, glidants. The diluent can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; the wetting agent can be water, ethanol, isopropanol, etc.; the binder can be starch paste, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic, gelatin, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.; the disintegrant can be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitan fatty acid ester, sodium dodecyl sulfate, etc.; the lubricant and glidant can be talc, silica, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc.

[0022] The tablets can be further formulated into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or bilayer tablets and multilayer tablets.

[0023] In order to formulate the dosage unit into capsules, the active ingredient, the pharmaceutical composition of the present invention, can be mixed with a diluent and a glidant, and the mixture can be directly placed into hard capsules or soft capsules. Alternatively, the active ingredient, the pharmaceutical composition of the present invention, can be first made into granules or pellets with a diluent, a binder and a disintegrant, and then placed into hard capsules or soft capsules. The various diluents, binders, wetting agents, disintegrants, glidants used for preparing the tablets of the pharmaceutical composition of the present invention can also be used for preparing the capsules of the pharmaceutical composition of the present invention.

[0024] In order to formulate the pharmaceutical composition of the present invention into injections, water, ethanol, isopropanol, propylene glycol or a mixture thereof can be used as a solvent and appropriate solubilizers, cosolvents, pH adjusters, osmotic pressure regulators commonly used in the art can be added. The solubilizer or cosolvent can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin, etc.; the pH adjuster can be phosphate, acetate, hydrochloric acid, sodium hydroxide, etc.; the osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate, etc. When preparing freeze-dried powder injections, mannitol, glucose, etc. can also be added as a bulking agent.

[0025] In addition, if necessary, colorants, preservatives, fragrances, flavoring agents or other additives can also be added to the pharmaceutical preparations.

[0026] In summary, due to the adoption of the above technical solutions, the beneficial effects of the present invention are:

[0027] The application of sesamoside in the medicament for the neuroprotective effect of Parkinson's disease. Specifically, a PD cell model with overexpression of α-Syn is established by transfecting α-Syn plasmid into mouse dopaminergic neuron MES23.5 cells, and sesamoside is added to intervene in the PD cells. The cell viability and cytotoxic damage of PD cells are detected by cell viability experiment and LDH release experiment to evaluate the effect of sesamoside on the cell viability of PD cells; the mitochondrial membrane potential (MMP) of cells is detected by Mito-Tracker staining experiment to evaluate the effect of sesamoside on the mitochondrial function of cells. The experimental results show that the treatment with 100 μM sesamoside can effectively increase the cell viability of PD cells, reduce cytotoxicity, and effectively increase the mitochondrial membrane potential of PD cells, and rescue mitochondrial damage. The above results prove that sesamoside can increase cell viability and reduce cytotoxicity by reducing mitochondrial damage in PD cells, and play a neuroprotective role in PD-damaged neurons. A PD mouse model is established by intraperitoneal injection of MPTP, and the PD model mice are intervened by gavage with sesamoside. Further, the open field test and rotarod test are used to evaluate the effect of sesamoside on the motor ability of mice. The results of animal experiments show that 10 mg / kg sesamoside can significantly improve the average movement speed of PD model mice in the open field test and increase the fall latency of PD mice in the rotarod test, indicating that sesamoside can effectively improve the motor function of Parkinson's disease mice. Therefore, sesamoside has good clinical application prospects for the treatment and / or prevention of Parkinson's disease. Brief Description of the Drawings

[0028] Figure 1 It is a diagram for establishing a PD cell model with overexpression of α-Syn of the present invention. Among them Figure 1 A is the protein electrophoresis result diagram of MES23.5 cells transfected with NC and SNCA plasmids for 48 h. Figure 1 B is the comparison result of the relative expression levels of α-Syn protein in the cell proteins of each group. In the figure, Con: blank cell group; NC: group transfected with NC plasmid; SNCA: group transfected with α-Syn plasmid; α-Syn: α-synuclein; β-actin: β-actin. n = 3, ****P < 0.0001.

[0029] Figure 2 It is a statistical chart of the significant inhibition of cytotoxic damage of PD model cells by sesamoside of the present invention.

[0030] Among them, the results of the cell viability detection experiment in Figure A show the relative cell viability of each group of cells. Figure B is the result of the cytotoxicity detection experiment, showing the percentage of LDH release of each group of cells. The labels in the figure are as follows: Con: blank cell group; NC: group transfected with NC plasmid; SNCA: groups transfected with α-Syn plasmid. n = 3, *P < 0.05, **P < 0.01, ****P < 0.0001.

[0031] Figure 3 This is the result diagram and statistical chart showing that sesamoside significantly inhibits mitochondrial damage in PD model cells in the present invention. Among them, Figure A is the staining result diagram of MitoTracker and Hoechst33342 for each group of cells. Figure B is the comparison of the relative fluorescence intensity values of MitoTracker staining for each group of cells. The labels in the figure are as follows: Con: blank cell group; NC: group transfected with NC plasmid; SNCA: group transfected with α-Syn plasmid; SNCA + Sesamoside: group transfected with α-Syn plasmid and intervened with Sesamoside. n = 3, **P < 0.01, ****P < 0.0001.

[0032] Figure 4 This is the result diagram showing that sesamoside significantly improves the motor ability of PD model mice in the present invention. Among them, Figure A is the open field movement trajectory diagram of each group of mice. Figure B is the statistical result diagram of the average movement speed of the open field experiment for each group of mice. Figure C is the statistical result diagram of the falling rod latency of the rotarod test for each group of mice. The labels in the figure are as follows: Con: control group; PD: Parkinson's disease group; Sesamoside: sesamoside. n = 5, **P < 0.01, ***P < 0.001, ****P < 0.0001. Detailed implementation manners

[0033] To make the above objects, features and advantages of the present invention more obvious and understandable, the following detailed description of the specific implementation manners of the present invention will be given in conjunction with the accompanying drawings. Many specific details are set forth in the following description in order to fully understand the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific implementations disclosed below.

[0034] Experiment:

[0035] 1. Materials and methods

[0036] 1.1 Cell culture and treatment

[0037] Establishment of PD cell model: Mouse dopaminergic neurons (MES23.5 cells) were cultured in DMEM / F12 medium (Gibco, New York, USA) containing 10% fetal bovine serum and Sato's. 2 μg of α-Syn plasmid or empty vector (NC) plasmid was transfected into each well of a 6-well plate using Lipofectamine 3000 (Gibco, New York, USA). The cells were divided into 3 groups: Con group, NC group, and SNCA group. The cells were treated for 48 h and then subjected to subsequent Western blotting detection.

[0038] Drug intervention: 100 ng of α-Syn plasmid (SNCA) or empty vector (NC) plasmid was transfected into each well of a 96-well plate using Lipofectamine 3000. 24 h after plasmid transfection, Sesamoside dissolved in DMSO (Sigma, MO, USA) was added to the cell culture medium overexpressing α-Syn protein, with final concentrations of 0 μM, 25 μM, 50 μM, and 100 μM, respectively. The cells were divided into 6 groups: Con group, NC group, SNCA-Sesamoside 0 μM group, SNCA-Sesamoside 25 μM group, SNCA-Sesamoside 50 μM group, and SNCA-Sesamoside 100 μM group. The cells were further treated for 24 h and then subjected to subsequent cell viability detection, cytotoxicity detection, and mitochondrial membrane potential detection.

[0039] 1.2 Western blotting experiment

[0040] Cells treated differently were collected and lysed according to the instructions of a cell protein preparation kit (Applygen, Beijing, China). The cells were separated and collected into different tubes. The protein concentration was evaluated using a BCA protein quantification kit (Thermo Fisher Scientific, Massachusetts, USA). Then, 20 μg of protein from each fraction was separated by SDS-PAGE and transferred to a PVDF membrane (Sigma, MO, USA). Then, it was blocked with 5% skim milk powder, and anti-α-Syn and anti-β-actin antibodies were added respectively and incubated overnight. The corresponding fluorescent secondary antibody was combined with the primary antibody at room temperature for 1 h. After four washes, the membrane was scanned and imaged using an ODYSSEY imaging system (LI-COR, Nebraska, USA).

[0041] 1.3 Cell viability detection

[0042] Using CellTiter The cell viability was detected by the AQueous One Solution Cell Proliferation Assay kit (Promega, WI, USA). The old medium of the cells in the 96-well plate was aspirated, and 100 μL of fresh medium was replaced in each well. 20 μL of CellTiter AQueous One Solution Reagent was added to the treated group of cells and incubated at 37 °C in a 5% CO 2 environment for 1 h. The absorbance value was read at a wavelength of 490 nm using an enzyme-linked immunosorbent assay (ELISA) reader.

[0043] 1.4 Cytotoxicity detection

[0044] The LDH release was detected using the CytoTox Non-Radioactive Cytotoxicity Assay kit (Promega, WI, USA) to evaluate cytotoxic damage. 50 μL of the old medium was taken from all test wells and control wells and transferred to a clean 96-well plate. 50 μL of CytoTox Reagent was added, and the mixture was incubated in the dark at room temperature for 30 min. The absorbance value was read at a wavelength of 490 nm using an ELISA reader.

[0045] 1.5 Detection of mitochondrial membrane potential (MMP)

[0046] The cell MMP was detected using a mitochondrial membrane potential detection kit (Beyotime, Shanghai, China). The old medium of the cells in the 96-well plate was aspirated, and the cells were washed once with PBS. 96.5 μL of binding buffer was added to each well of the cells, followed by the addition of 2 μL of MitoTracker Red CMXRos staining solution and 5 μL of Hoechst 33342 staining solution. The mixture was gently mixed and incubated in the dark at room temperature for 20 min. Then, it was observed under a fluorescence microscope. MitoTracker Red CMXRos showed red fluorescence, and Hoechst 33342 showed blue fluorescence.

[0047] 1.6 Establishment of the PD model and Sesamoside intervention

[0048] Twenty-five 8-week-old male C57 / BL6N mice were purchased from Cyagen Model Organism Research Center (Taicang) Co., Ltd. (production license number: SCXK (Jiangsu) 2018-0003), and were housed in the SPF animal room of Guilin Medical University, with free access to food and water, and a 12h / 12h day-night cycle. They were randomly divided into 5 groups of 5 mice each. Four of the groups were intraperitoneally injected with MPTP for 7 days to establish a PD mouse model. Three of these groups were respectively pre-gavaged with Sesamoside at 5mg / kg, 7.5mg / kg, and 10mg / kg for 7 days, and continuously gavaged for 7 days during the PD modeling process to establish PD models intervened with different concentrations of Sesamoside, namely the PD+5mg / kg Sesamoside group, the PD+7.5mg / kg Sesamoside group, and the PD+10mg / kg Sesamoside group; the fourth group was pre-gavaged with the same volume of normal saline for 7 days and continuously gavaged for 7 days during the modeling process as the PD group; the fifth group was pre-gavaged with normal saline for 14 days and intraperitoneally injected with normal saline starting from the 8th day as the Con group. After the modeling, the motor ability of each group of mice was detected by behavioral tests. The open field test was used to evaluate the spontaneous motor ability of the mice, that is, the spontaneous movement trajectory and distance of the mice within 5 minutes were recorded, and the average movement speed was calculated according to the distance and time; the rotarod test was used to detect the coordinated motor ability of the mice, that is, first trained at a speed of 4rpm / min for 3 times, 2 minutes each time, and then the rotarod speed was adjusted to accelerate from 4rpm / min to 40rpm / min within 5 minutes, and the time experienced by each mouse falling off the rotarod was recorded, that is, the fall latency of the rotarod.

[0049] 1.7 Statistical analysis

[0050] Data are expressed as mean ± standard deviation. Statistical analysis was performed using GraphPad Prism software 9.0 (GraphPad, California, USA). One-way ANOVA was used to evaluate the differences between groups, and then Tukey's multiple comparison test was used. P<0.05 was considered statistically significant.

[0051] 2. Results

[0052] 2.1 Establishment of the PD model cell model

[0053] The WB results showed that compared with the Con group (100%) and the NC group (92.75%), the α-Syn expression in the α-Syn transfection group (SNCA group, 2596.36%) was significantly increased (P<0.0001), indicating that the PD cell model with overexpression of α-Syn was successfully established ( Figure 1 ).

[0054] 2.2 Sesamoside significantly inhibits cytotoxic damage in PD model cells

[0055] Cell viability assay and LDH release experiment results showed that compared with the Con group (cell viability 100%, LDH release 100%) and the NC group (cell viability 101.99%, LDH release 104.57%), the cell viability (42.42%) of the α-Syn transfection group (SNCA-Sesamoside 0 μM group) decreased significantly, and the LDH release (205.93%) increased significantly (P < 0.0001, P < 0.0001). Compared with the SNCA-Sesamoside 0 μM group, after treatment with 25 μM Sesamoside, the cell viability increased to 47.18%, and the LDH release decreased to 186.43%; after treatment with 50 μM Sesamoside, the cell viability increased to 54.37%, and the LDH release decreased to 176.40%; after treatment with 100 μM Sesamoside, the cell viability increased to 70.36%, and the LDH release decreased to 149.05%; among them, the treatment effect of 100 μM Sesamoside was the best (P < 0.05, P < 0.01)( Figure 2 A, B).

[0056] 2.3 Sesamoside significantly inhibits mitochondrial function damage in PD model cells

[0057] Mitochondrial membrane potential detection results showed that compared with the Con group (100%) and the NC group (85.77%), the mitochondrial membrane potential (MitoTracker fluorescence intensity, 32.62%) of the α-Syn transfection group (SNCA group) decreased significantly (P < 0.0001). Compared with the SNCA group, after treatment with 100 μM Sesamoside, the MitoTracker fluorescence intensity (62.99%) increased significantly (P < 0.01)( Figure 3 A, B).

[0058] 2.4 Sesamoside significantly improves the motor ability of PD model mice

[0059] Open field experiment results showed that compared with the Con group, the movement trajectories of mice in the PD group were significantly sparser and concentrated around the four sides, while the trajectories of mice intervened with different concentrations of Sesamoside gradually became denser, especially in the group of mice intervened with 10 mg / kg Sesamoside( Figure 4A). Compared with the Con group (64.71 mm / s), the open-field movement speed of PD group mice decreased significantly to 31.76 mm / s (P < 0.0001); while the average open-field movement speed of mice in the 5 mg / kg Sesamoside intervention group increased to 40.85 mm / s, that of mice in the 7.5 mg / kg Sesamoside intervention group increased to 46.33 mm / s, and that of mice in the 10 mg / kg Sesamoside intervention group increased to 54.33 mm / s. Among them, the average open-field movement speed of mice in the 10 mg / kg Sesamoside intervention group increased most significantly (P < 0.0001). In addition, the results of the rotarod test showed that compared with the Con group (265.8 s), the falling latency of the rotarod test of PD group mice was significantly shortened to 133.8 s (P < 0.001); while the falling latency of the rotarod test of mice in the 5 mg / kg Sesamoside intervention group increased to 163.0 s, that of mice in the 7.5 mg / kg Sesamoside intervention group increased to 194.5 s, and that of mice in the 10 mg / kg Sesamoside intervention group increased to 228.8 s. Among them, the falling latency of the rotarod test of mice in the 10 mg / kg Sesamoside intervention group increased most significantly (P < 0.01)( Figure 4 B, C).

[0060] In summary, 100 μM sesamoside treatment can effectively increase the cell viability of PD cells, reduce cytotoxicity, and effectively increase the mitochondrial membrane potential of PD cells, rescuing mitochondrial damage; 10 mg / kg sesamoside treatment can effectively increase the average open-field movement speed of PD mice and prolong the falling latency of the rotarod test. The above results prove that sesamoside can increase cell viability, reduce cytotoxicity, and improve the motor ability of PD mice by reducing mitochondrial damage in PD cells, showing neuroprotective effects on PD and having good clinical application prospects.

[0061] The above-described embodiments merely represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.

Claims

1. Application of sesame glycosides as neuroprotective drugs for Parkinson's disease.

2. The use of flaxseed glycosides in a drug for neuroprotection of Parkinson's disease according to claim 1, characterized in that: The sesame glycosides play a protective role in neuronal damage.

3. The use of flaxseed glycosides in a drug for neuroprotection of Parkinson's disease according to claim 1, characterized in that: The sesame glycosides reduce the damage and cytotoxicity of dopaminergic neuron MES23.5 cells induced by overexpression of α-Syn protein, improve the mitochondrial dysfunction caused by overexpression of α-Syn protein in dopaminergic neurons MES23.5, alleviate movement disorders in Parkinson's disease mice, and thus play a protective role in Parkinson's disease nerve damage.

4. A drug for protecting Parkinson's disease nerves, characterized in that: The main component of the medicine is sesame glycoside.

5. The drug for protecting Parkinson's disease nerves according to claim 4, characterized in that: The effective concentration of the sesame glycosides for reducing the damage and cytotoxicity of dopaminergic neuron MES23.5 cells induced by overexpression of α-Syn protein in vitro is 25 μM-100 μM.

6. The drug for protecting Parkinson's disease nerves according to claim 4, characterized in that: The drug is prepared into a clinically acceptable drug preparation with sesame glycosides as the main component and pharmaceutically acceptable excipients or auxiliary components.

7. The drug for protecting Parkinson's disease nerves according to claim 4, characterized in that: The preparation of the drug includes any one of tablets, pills, capsules, granules, syrups, powders, granules, suppositories, drops, emulsions, solutions and suspensions.

8. A pharmaceutical composition for treating and / or preventing Parkinson's disease, characterized in that: The pharmaceutical composition is prepared into a clinically acceptable pharmaceutical preparation with sesame glycosides as the main component and pharmaceutically acceptable excipients or auxiliary components.

9. The pharmaceutical composition for treating and / or preventing Parkinson's disease according to claim 8, characterized in that: The content of the safflower glycosides in the pharmaceutical composition is 5 mg / kg-10 mg / kg.

10. The pharmaceutical composition for treating and / or preventing Parkinson's disease according to claim 8, characterized in that: The preparation of the drug includes any one of tablets, pills, capsules, granules, syrups, powders, granules, suppositories, drops, emulsions, solutions and suspensions.

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