Application of poliumoside in prevention and treatment of Parkinson's disease

Abstract

The invention belongs to the technical field of medicines, and discloses application of poliumoside to prevention and treatment of Parkinson's disease. Specifically, the invention discloses application of poliumoside as a compound shown in a formula (I) in the aspect of preventing and treating Parkinson's disease. Pharmacological experiments prove that after 14 days of administration of the poliumoside, the impairment of motor coordination function caused by MPTP-induced Parkinson's disease can be obviously improved, the reduction of the expression level of brain nigra tyrosine hydroxylase caused by MPTP is improved, and the result shows that the poliumoside has obvious pharmacological activity for preventing and treating Parkinson's disease. Therefore, poliumoside can be used for preparing the medicine for preventing and treating Parkinson's disease, and has high clinical application value and development prospect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to the use of ginsenoside in the preparation of drugs for the prevention and treatment of Parkinson's disease. Background Technology

[0002] Parkinson's syndrome is a clinical syndrome related to motor function, characterized by tremor, decreased motor function, rigidity, and balance disorders. It can be divided into primary Parkinson's syndrome and secondary Parkinson's syndrome. In primary Parkinson's syndrome, Parkinson's disease (PD) accounts for the vast majority of cases. It is a degenerative disease of the central nervous system that occurs in the elderly, clinically characterized by tremor, rigidity, and bradykinesia, accompanied by degeneration and death of dopaminergic neurons in the substantia nigra and decreased dopamine neurotransmitter levels in the striatum. Secondary Parkinson's syndrome is caused by drugs, toxins, head trauma, metabolic diseases, infections, cerebrovascular diseases, etc. It is characterized by degeneration and necrosis of dopaminergic neurons in the substantia nigra and striatum, leading to reduced dopamine synthesis or damage to the dopamine receptor system, resulting in a series of neurological dysfunctions. Currently, the main drugs for treating Parkinson's disease include levodopa tablets, amantadine hydrochloride, trihexyphenidyl hydrochloride, selegiline hydrochloride, and ropinirole hydrochloride, but their clinical application has certain limitations. Therefore, it is of great significance to develop new drugs for the prevention and treatment of Parkinson's disease.

[0003] 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model mice are commonly used animal models for evaluating drugs for the prevention and treatment of Parkinson's disease. Tyrosine hydroxylase (TH) is a key enzyme in the dopamine biosynthesis pathway and a recognized marker of dopaminergic neurons. This study evaluated the anti-PD effect of sclerotinib in MPTP-induced PD model mice.

[0004] Poliumoside (POL) is a major active ingredient in the traditional Chinese medicines *Cistanche sinensis* G. Beck and *Callicarpa kwangtungensis* Chun, possessing anti-inflammatory, antioxidant, and hemostatic biological activities. Currently, there are no reports on the use of poliumoside in the prevention and treatment of Parkinson's disease. Summary of the Invention

[0005] One of the problems to be solved by this invention is to provide the use of ginsenosides in improving motor coordination impairment in Parkinson's mice.

[0006] The second problem to be solved by this invention is to provide the use of ginsenoside A in improving the reduced expression of tyrosine hydroxylase in the substantia nigra striatum of Parkinson's disease mice.

[0007] To solve the technical problem of this invention, the present invention provides the following technical solution:

[0008] The first aspect of the present invention is to provide the use of the compound sclerotinol as shown in general formula (I) or a pharmaceutically acceptable salt thereof in the preparation of drugs for the prevention and treatment of Parkinson's disease;

[0009]

[0010] The Parkinson's disease mentioned includes Parkinson's motor coordination impairment.

[0011] The stroke mentioned includes decreased expression of tyrosine hydroxylase in the substantia nigra striatum after Parkinson's disease.

[0012] The application of compound scleroside or its pharmaceutically acceptable salt, as shown in general formula (I), in the preparation of drugs for the prevention and treatment of motor coordination impairment after Parkinson's disease and the reduction of tyrosine hydroxylase expression in the substantia nigra striatum.

[0013] This invention uses MPTP to induce a Parkinson's disease model mouse and evaluates the effect of ginsenoside on Parkinson's disease. It found that ginsenoside can improve the motor coordination impairment and reduce the tyrosine hydroxylase in the substantia nigra striatum of Parkinson's mice.

[0014] This invention also relates to pharmaceutical compositions of the compounds of this invention and conventional pharmaceutical excipients or adjuvants.

[0015] Pharmaceutical compositions of the compounds of the present invention can be prepared according to methods known in the art. For this purpose, if desired, the compounds of the present invention can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to formulate suitable administration or dosage forms for use as human or veterinary medicine.

[0016] The compounds of this invention or pharmaceutical compositions containing them can be administered in unit dose form via enteral or non-enteric routes, such as oral, intramuscular, subcutaneous, nasal, oral mucosa, skin, peritoneum, or rectum.

[0017] The compounds of this invention or pharmaceutical compositions containing them can be administered via injection. Injection includes intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, and acupoint injection, etc.

[0018] Dosage forms can be liquid or solid. Liquid dosage forms include true solutions, colloids, microparticles, emulsions, and suspensions. Other dosage forms include tablets, capsules, pellets, aerosols, pills, powders, solutions, suspensions, emulsions, granules, suppositories, and lyophilized powder injections.

[0019] The compounds of this invention can be formulated into conventional formulations, sustained-release formulations, controlled-release formulations, targeted formulations, and various microparticle delivery systems.

[0020] Beneficial technical effects: This compound has outstanding pharmacological activity and is suitable for use in the treatment of thrombotic stroke. Attached Figure Description

[0021] Figure 1 Effects of sclerotin on motor coordination in MPTP-induced Parkinson's mice. Values ​​are expressed as mean ± SD. Compared with the normal control group, ##P<0.01; compared with the MPTP model group, **P<0.01.

[0022] Figure 2 Effects of ginsenoside on the expression level of MPTP-induced tyrosine hydroxylase in the substantia nigra and striatum of Parkinson's mice. Values ​​are expressed as mean ± SD. Compared with the normal control group, #P<0.05; compared with the MPTP model group, *P<0.01. Detailed Implementation

[0023] Effects of ginsenoside on stroke mice

[0024] 1. Experimental Methods

[0025] 1.1 Animal grouping and administration

[0026] After acclimatization, C57BL / 6J mice were randomly divided into a normal control group, an MPTP model group, and a poloxacillin (POL) treatment group, with 10 mice in each group. The MPTP model group was established by intraperitoneal injection of MPTP 30 mg / kg for 5 consecutive days (once daily). The poloxacillin treatment group received poloxacillin 20 mg / kg / day by gavage 1 hour before MPTP modeling (same as the MTPT model group) for 14 consecutive days. The normal control group used an equal volume of physiological saline and solvent as a control. Various tests were performed 14 days after poloxacillin administration.

[0027] 1.2 Rotator test to assess the motor coordination ability of mice

[0028] Mice were tested after adaptive training. Five mice were placed on a rotundus apparatus at a time, one mouse per compartment. The rotundus speed was gradually increased from 4 rpm to 40 rpm over 5 minutes, and the time from the start of the rotundus to the mouse falling off was recorded. Three replicate experiments were conducted, each lasting 5 minutes with a 30-minute interval. The average time it took for the mouse to fall off the rotundus was calculated.

[0029] 1.3 Western blot analysis of tyrosine hydroxylase (TH) expression in the substantia nigra striatum of mouse brain.

[0030] Brain tissue was lysed with RIPA protein extraction buffer containing a mixture of protease inhibitors and phosphatase inhibitors, and the total protein concentration was then quantified using a BCA kit. Samples were separated by SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membranes; the samples were blocked at room temperature (RT) for 2 hours with 5% skim milk powder dissolved in Tris buffer containing 0.1% Tween 20 (TBST); the membranes were then incubated overnight at 4°C with primary antibodies against TH (1:1000) or β-actin (1:1000); subsequently incubated at RT for 1 hour with Rb or Ms-labeled secondary antibodies; the target protein signals were detected and digitized using ECL solution and Image J program, and the relative expression level of TH protein was expressed as TH / β-actin.

[0031] 2. Experimental Results

[0032] 2.1 Effects of sclerotin on motor coordination in MPTP-induced Parkinson's mice

[0033] The motor coordination ability of mice was assessed using a rotarod apparatus. Compared with the control group, the residence time of mice in the MPTP model group was reduced, while the residence time of mice in the ginsenoside-treated group was significantly higher than that in the MPTP model group, indicating that ginsenoside significantly improved the motor coordination ability of mice (Table 1). Figure 1 ).

[0034] Table 1. Effects of sucralose on MPTP-induced motor coordination in mice

[0035]

[0036]

[0037] Numerical values ​​are expressed as mean ± SD. Compared with the normal control group, ##P<0.01; compared with the MPTP model group, *P<0.05.

[0038] 2.2 Effects of ginsenoside on MPTP-induced expression of tyrosine hydroxylase in the substantia nigra and striatum of Parkinson's mice

[0039] Tyrosine hydroxylase is a key enzyme in the dopamine biosynthesis pathway and a recognized biomarker of dopaminergic neurons. Compared with the control group, the expression of tyrosine hydroxylase in the substantia nigra and striatum of mice in the MPTP model group was reduced; compared with the MPTP model group, the expression of tyrosine hydroxylase in the striatum of mice in the sclerotinia glycoside-treated group was significantly increased (Table 2). Figure 2 ).

[0040] Table 2. Effects of sclerotinib on MPTP-induced expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum of mice.

[0041] Group Tyrosine hydroxylase (TH) expression normal control group 1.27±0.03 MPTP model group 0.65±0.14## Jinshisin dosing group 1.13±0.30*

[0042] Numerical values ​​are expressed as mean ± SD. Compared with the normal control group, #P<0.05; compared with the MPTP model group, *P<0.05.

Claims

1. The use of the compound sclerotinol of general formula (I) or a pharmaceutically acceptable salt thereof in the preparation of drugs for the prevention and treatment of Parkinson's disease; 2. The application according to claim 1, characterized in that, The Parkinson's disease mentioned includes post-Parkinson's disease motor coordination impairment.

3. The application according to claim 1, characterized in that, The Parkinson's disease mentioned includes reduced expression of tyrosine hydroxylase in the substantia nigra striatum of the hindbrain.

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