Application of Rg1 in Parkinson's syndrome with aggravated emotional stress and alpha-synucleinopathies

Abstract

The invention belongs to the technical field of medicines, and relates to application of a compound Rg1 as shown in a formula I in preparation of medicines for preventing or treating Parkinson's syndrome and alpha-synucleinopathy with aggravated emotion stress. It is found that the compound Rg1 can significantly improve common symptoms of clinical Parkinson's patients, and the common symptoms are shown as improvement of exercise coordination, improvement of motion retardation and balance ability and improvement of limb grasping ability. The Rg1 can obviously increase the content of dopaminergic neurons and fibers of dopaminergic neurons at nigra and striatum parts induced by emotion stress and gene interaction; the alpha synuclein aggregation induced by the model is obviously reduced. The compound can be used for preparing drugs for preventing and treating Parkinson's syndrome and alpha-synucleinopathy with aggravated emotion stress. # imgabs0 #

Description

Technical Field

[0001] The present invention mainly relates to the use of a compound Rg1 in the preparation of a drug for preventing or treating Parkinson's syndrome aggravated by emotional stress and alpha-synuclein-related diseases, and belongs to the field of medical technology. Background Art

[0002] Parkinson's disease (PD) is a common neurodegenerative disease in the elderly. The main pathological features of PD are progressive degeneration of dopaminergic neurons in the substantia nigra of the midbrain and accumulation of Lewy bodies, which lead to severe motor dysfunction, including tremor, muscle rigidity, bradykinesia, postural balance disorders, and non-motor symptoms such as sleep disorders, olfactory disorders, autonomic dysfunction, cognitive and mental disorders, which seriously threaten the health of the elderly. At present, clinical drugs and surgical interventions can only relieve PD symptoms, but cannot delay the progression of the disease. The development of innovative drugs for PD treatment faces difficulties.

[0003] The interaction between environmental stress and genetic factors is the key link in accelerating the progression of PD: (1) Genetic factors are the basic cause of PD. α-Synuclein (αSyn) is the main component of Lewy bodies, and its missense mutations (A53T, A30P, E46K) are associated with familial PD. The αSyn gene (SNCA) has also been shown by genome-wide association studies to be one of the high-risk factors for sporadic PD. The αSyn A53T transgenic mouse model overexpresses human mutant αSyn and is a commonly used PD susceptibility gene model. (2) Environmental stress is a definite factor that aggravates the pathological process of PD. Emotional stress may cause movement disorders in non-PD patients and also affect the disease course of PD patients. Studies have shown that psychological stress caused by social environment and pressure is closely related to the early onset of PD, increased incidence, and shortened levodopa honeymoon period. In people who have experienced major emotional trauma (Far Eastern prisoners of war after release), the incidence of PD is much higher than that of their peers. Case reports show that young women continue to experience PD-like symptoms within a week after being mentally stimulated. Clinical studies have found that depression occurs before or with PD symptoms, indicating a poor prognosis for PD. Compared with healthy people, PD patients have significantly elevated cortisol levels, and cortisol levels are positively correlated with gait abnormalities. A study of 358 PD patients showed that the level of COVID-19-related mood disorders was significantly positively correlated with the severity of PD symptoms, and psychological stress can lead to rapid deterioration of PD symptoms. Mechanism analysis found that the nigrostriatal dopaminergic system is most sensitive to stress and is more susceptible to external stress; chronic stress leads to decreased striatal DA levels and decreased dopaminergic neuron activity in rodents. Based on the above research background, 10-month-old αSyn A53T transgenic mice were subjected to restraint stress for 4 weeks (4 hours / day) and found to show more severe PD-like behavioral and pathological characteristics than wild-type mice of the same age, proving that this model can be used as a PD model aggravated by chronic stress and gene interaction, and can be used for drug evaluation to detect the therapeutic effect of active substances on the pathological process of PD aggravated by emotional stress.

[0004] Ginsenoside Rg1, molecular formula is C 42 H 72 O 14 MW: 801, structural formula is as follows. So far, there is no application of this compound for Parkinson's syndrome aggravated by emotional stress and α-synuclein related diseases. The inventors found that Rg1 can significantly reduce Parkinson's symptoms aggravated by emotional stress, alleviate pathological damage to dopaminergic neurons, and reduce the formation of αSyn aggregates, indicating that it has a significant therapeutic effect on the PD process aggravated by emotional stress and α-synuclein related diseases.

[0005] Summary of the invention

[0006] The present invention provides a new therapeutic use of Rg1, which is to prevent and treat Parkinson's syndrome aggravated by emotional stress and alpha synuclein disease caused by emotional stress.

[0007] To this end, the present invention provides a new use of a drug, namely, using the compound Rg1 as shown in Formula I to prepare a drug for preventing and treating Parkinson's syndrome aggravated by emotional stress and α-synuclein disease caused by emotional stress.

[0008]

[0009] Furthermore, the emotional stress is a mental stress state caused by various pressures, and its causes include but are not limited to social environment, competitive pressure, natural environment, and long-term chronic disease causes.

[0010] Furthermore, the Parkinson's syndrome includes primary Parkinson's syndrome, i.e. Parkinson's disease, symptomatic Parkinson's syndrome, hereditary degenerative Parkinson's syndrome and Parkinson's plus syndrome.

[0011] Furthermore, the Parkinson's symptoms include motor and non-motor symptoms. Motor symptoms include resting tremor, muscle rigidity and bradykinesia, and balance disorders. Non-motor symptoms include abnormal smell, mood changes, and cognitive impairment.

[0012] Furthermore, the α-synuclein-related diseases include Parkinson's disease, multiple system atrophy, and Lewy body dementia.

[0013] Furthermore, the effects of the compound Rg1 include both therapeutic and preventive effects;

[0014] The second aspect of the technical solution of the present invention provides a pharmaceutical composition for use in the preparation of a method for preventing or treating Parkinson's syndrome aggravated by emotional stress and α-synuclein disease caused by emotional stress. The pharmaceutical composition comprises the compound Rg1 described in the first aspect and a pharmaceutically acceptable carrier or excipient.

[0015] The beneficial effects of the present invention are: the present invention evaluates the therapeutic effect of Rg1 on the behavioral disorders of Parkinson's disease induced by emotional stress and gene interaction through the rotating rod test, the climbing pole test, and the balance beam walking test; the grip test detects limb strength; and the damage of dopaminergic neurons is detected by tyrosine hydroxylase (TH) staining in the striatum and substantia nigra, the main pathological brain areas of Parkinson's disease, and α-synuclein aggregates are detected by thioflavin S (ThS), and the effect of compound Rg1 on the pathology of Parkinson's disease induced by emotional stress and gene interaction is evaluated. The results show that Rg1 can significantly increase the residence time on the rotating rod compared with the model group, shorten the time to climb down from the top of the pole and cross the balance beam, improve the common movement coordination of Parkinson's patients in clinical practice, and improve bradykinesia and balance ability; the grip experiment shows that Rg1 can significantly increase the grasping ability and relieve limb tremor. Pathological examination showed that Rg1 could significantly increase the content of dopaminergic neurons and their fibers in the substantia nigra and striatum induced by emotional stress and gene interaction, and significantly reduce the aggregation of synuclein induced by the model. Ginsenoside Rg1 provides an effective solution for the prevention and treatment of Parkinson's syndrome aggravated by emotional stress and alpha synuclein disease caused by emotional stress. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 Shown is the effect of Rg1 on motor behavior disorders in PD model mice aggravated by emotional stress and gene interaction ( n=8). The experimental groups were control group, model group, and model+drug administration group; ### Compared with the control group, P < 0.001; ** Compared with the model group, P<0.01, *** Compared with the model group, P<0.001.

[0017] Figure 2 Shown is the effect of Rg1 on TH expression in the striatum of PD model mice with aggravated emotional stress and gene interaction ( n=5). The experimental groups were control group, model group, and model+drug administration group; ### Compared with the control group, P < 0.001; *** Compared with the model group, P<0.001.

[0018] Figure 3 The figure shows the effect of Rg1 on the expression of TH in the substantia nigra of PD model mice with aggravated emotional stress and gene interaction ( n=5). The experimental groups were control group, model group, and model+drug administration group; ### Compared with the control group, P < 0.001; *** Compared with the model group, P<0.001.

[0019] Figure 4Shown is the effect of Rg1 on αSyn aggregation in PD model mice with aggravated emotional stress and gene interaction ( n=5). The experimental groups were control group, model group, and model+drug administration group; ### Compared with the control group, P < 0.001; *** Compared with the model group, P<0.001.

[0020] Figure 5 The results show the effect of different concentrations of Rg1 on the aggregation of αSyn in SH-SY5Y-αSyn A53T cells treated with CORT ( n=4). The experimental groups were control group, CORT model group, and different concentration drug administration groups: Rg1 0.1μM group, Rg1 1μM group, and Rg1 10μM group; ### Compared with the control group, P < 0.001; ** Compared with the CORT model group, P<0.01, *** Compared with the CORT model group, P<0.001. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings, but the present invention is not limited to the illustrated implementation scope.

[0022] Example 1: Effect of Rg1 on motor behavior disorders in PD model mice aggravated by emotional stress and gene interaction

[0023] Experimental materials: SPF-grade 10-month-old C57 mice, half male and half female, were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd., with a certificate number of SCXK (Beijing) 2019-0010. SPF-grade 10-month-old αSyn A53T mice, half male and half female, were raised in Sibeifu (Beijing) Biotechnology Co., Ltd., with a certificate number of SCXK (Beijing) 2019-0010. Rg1 was purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0024] Experimental groups: 10 male C57 mice aged 10 months were used as the control group, and 20 αSyn A53T mice aged 10 months were randomly divided into the model group and the model + drug administration group, with 10 mice in each group. The drugs were dissolved in ultrapure water. Except for the control group, all groups were subjected to chronic restraint stress modeling. The drug administration group was given Rg1 40 mg / kg by gavage during the modeling period, and the control group was given the same volume of solvent control ultrapure water.

[0025] Establishment of a PD model with aggravated interaction between emotional stress and genes: 10-month-old αSyn A53T transgenic mice were modeled by chronic restraint stress. The animals were placed in a mouse restraint cylinder, unable to move freely, ensuring normal breathing without pain. They were stressed for 4 hours every day for 4 weeks, 6 days a week, and the stress was carried out at different times between 10:00 and 20:00 every day to minimize animal adaptation. The control group was placed in a corresponding conventional breeding cage and was also given fasting and water deprivation treatment during the stress period to exclude weight differences caused by different feeding durations.

[0026] Rotarod test: Used to detect the motor coordination ability of animals. The mice were placed on the rotarod for testing. The rotarod was set to increase from 5 rpm to 30 rpm within 300 s, and the falling time of the mice was recorded. The average value of 3 tests was statistically analyzed.

[0027] Pole climbing test: Used to evaluate the motor retardation symptoms of animals. A pole climbing device wrapped with gauze, 50 cm high and 1 cm in diameter, was placed in a rat breeding cage, and the bottom was covered with bedding equal in height to the base of the pole climbing device to prevent the mice from being injured when they fell. After the mice adapted to the environment, they were trained for pole climbing to ensure that all mice had the awareness of climbing down. During the pole climbing test, they were placed at the top of the wooden pole, and the time for the mice to climb from the top to the bottom was recorded. The average value of 3 tests was statistically analyzed.

[0028] Balance beam test: Used to detect the motor coordination and integration function of mice. The balance beam device is a wooden pole with a length and width of 1×75 cm, placed at a height of about 60 cm from the ground. A black box that makes the mice feel safe is placed at one end of the wooden pole. First, the mice were trained, a total of four times, with an interval of at least 30 min each time to ensure that the mice had the awareness of crossing the balance beam to reach the black box. During the test, the time for the mice to cross the balance beam to reach the box was recorded, and the average value of 3 tests was statistically analyzed.

[0029] Grip strength test: Used to evaluate the limb strength of mice. First, the mice were gently placed on the grip strength plate. Hold the mouse's tail and gently pull it backward horizontally. After the mouse's front paws firmly grasped the grip strength plate, pull it backward with uniform force until they let go, and record the maximum grip strength (g) at this time. The mice were tested 3 times, with an interval of at least 30 min each time. Finally, the average value of 3 tests was selected for statistical analysis.

[0030] Statistics and analysis: All data are expressed as and one-way ANOVA was used for statistical analysis of the data (Prism 8.0), with Dunnett’s test as the Post hoc test and P<0.05 as the standard for statistical difference.

[0031] Results: As shown in Table 1 and Figure 1The results of the study on the effect of Rg1 on the motor behavior of PD model mice aggravated by emotional stress and gene interaction showed that in the rotarod test, the model group mice stayed on the rotarod for a significantly shorter time than the control group, indicating motor coordination disorder (65.29±10.77, P<0.001). Compared with the model group, the Rg1-administered group could significantly improve the motor coordination ability of mice (137.5±14.73, P<0.01). In the pole climbing test, compared with the control group, the time required for the model group mice to climb from the top to the bottom was significantly prolonged (17.13±2.938, P<0.001). Compared with the model group, the Rg1-administered group could significantly improve the phenomenon of slow movement of mice (8.325±1.96, P<0.001). In the balance beam test, compared with the control group, the model group mice took longer to cross the balance beam (17.58±1.166, P<0.001), and compared with the model group, the Rg1-administered group could significantly shorten the time to cross the balance beam (10.21±1.388, P<0.001), indicating that the balance ability was significantly improved. In the grip test, compared with the control group, the forelimb grip of the model group mice was significantly weakened (167.1±15.42, P<0.001), and compared with the model group, the Rg1-administered group could significantly increase the forelimb grip of the mice (274.9±11.12, P<0.001), indicating that this experimental system can be used to evaluate the effect of Rg1 on the behavioral disorders of Parkinson's disease induced by emotional stress and gene interaction.

[0032] Table 1 Effects of Rg1 on motor behavior of PD model mice in which emotional stress and gene interaction are aggravated

[0033] Group Rotating rod(s) Climbing pole(s) Balance beam(s) Grip force(g) Control group 175.1±52.01 6.325±0.6453 8.55±0.9196 352.3±25.57 Model Group <![CDATA[65.29±10.77 ### ]]> <![CDATA[17.13±2.938 ### ]]> <![CDATA[17.58±1.166 ### ]]> <![CDATA[167.1±15.42 ### ]]> Model+drug group <![CDATA[137.5±14.73 ** ]]> <![CDATA[8.325±1.96 *** ]]> <![CDATA[10.21±1.388 *** ]]> <![CDATA[274.9±11.12 *** ]]>

[0034] Note: ### P<0.001vs. control group; ** P<0.01, *** P<0.001vs. model group

[0035] Example 2: Effect of Rg1 on TH expression in PD model mice with aggravated emotional stress and gene interaction

[0036] TH immunohistochemical analysis: Tyrosine hydroxylase (TH) is crucial in the synthesis of dopamine. Its functional deficiency or insufficient expression directly affects the synthesis and secretion of dopamine. Paraffin sections were dewaxed with xylene, dehydrated with ethanol step by step, and microwaved for 10 min in 0.01 M citric acid buffer for antigen repair. They were soaked in 0.5% Triton X-100 / PBS for 10 min to increase the permeability of cell membrane to antibodies. 3% H 2 O 2Incubate for 10 min to inactivate endogenous catalase, and block with 5% BSA for 30 min to eliminate nonspecific binding. After incubation with primary antibody at 4°C overnight, wash off the primary antibody with phosphate buffered saline containing 0.05% Tween (PBST) (10 min × 3 times) the next day, incubate with corresponding horseradish peroxidase-labeled secondary antibody at room temperature for 2 h, wash off the secondary antibody, develop color with DAB, seal the slide, take pictures under light microscope, and use Image J to count the data. + Fiber optical density (IOD) and TH + Cell number.

[0037] Statistics and analysis: All data are The data were analyzed statistically using one-way analysis of variance (Prism 8.0), Dunnett's test was used as a post hoc test, and P < 0.05 was set as the standard of statistical significance.

[0038] Results: As shown in Table 2 and Figure 2 and Figure 3 The results showed that in the striatum, compared with the control group, the optical density of TH-positive fibers in the model group was significantly reduced (0.3889±0.0916, P<0.001). Compared with the model group, the Rg1-administered group could significantly increase the optical density of TH-positive fibers ( Figure 2 , 0.7575±0.02233, P<0.001). In the substantia nigra compacta, compared with the control group, the optical density of TH-positive fibers in the model group was significantly reduced (0.2695±0.03347, P<0.001). Compared with the model group, the Rg1-treated group could significantly increase the optical density of TH-positive fibers ( Figure 3 , 0.7425±0.02825, P<0.001), indicating that this experimental system can be used to evaluate the effect of Rg1 in treating Parkinson's pathological damage induced by emotional stress and gene interaction.

[0039] Table 2 Effects of Rg1 on TH expression in PD model mice with aggravated emotional stress and gene interaction

[0040]

[0041]

[0042] Note: ### P<0.001vs. control group; *** P<0.001vs. model group

[0043] Example 3: Effect of Rg1 on αSyn aggregation in PD model mice with aggravated emotional stress and gene interaction

[0044] Thioflavin S (ThS) staining of tissue sections: Thioflavin S staining was used to detect the aggregation of αSyn. Paraffin sections were dewaxed with xylene, dehydrated with ethanol step by step, stained with 0.1% Thioflavin S for 10 min, then differentiated with 70% alcohol for 5 min, stained with Hochest 33342 (1:1000) at 37°C for 10 min, washed with PBS for 5 min × 3 times, and then sealed. Thioflavin S-positive inclusion bodies were observed under a fluorescence microscope, and the percentage of cells without ThS-positive inclusion bodies was counted (the number of cells without ThS-positive inclusion bodies / the total number of cells in each field of view × 100%).

[0045] Statistics and analysis: All data are The data were analyzed statistically using one-way analysis of variance (Prism 8.0), Dunnett's test was used as a post hoc test, and P < 0.05 was set as the standard of statistical significance.

[0046] Results: As shown in Table 3 and Figure 4 The results of the study on the effect of Rg1 on αSyn aggregation in PD model mice aggravated by emotional stress and gene interaction showed that in the substantia nigra compacta, compared with the control group, the proportion of cells without ThS-positive inclusions in the model group mice was significantly reduced (18.1%±2.828%, P<0.001). Compared with the model group, the Rg1-treated group could significantly increase the proportion of cells without ThS-positive inclusions (75.99%±2.843%, P<0.001), indicating that Rg1 has a significant inhibitory effect on the aggregation of α-synuclein in PD model mice induced by emotional stress and gene interaction.

[0047] Table 3 Effects of Rg1 on αSyn aggregation in PD model mice with aggravated emotional stress and gene interaction

[0048] Group Number of cells without ThS (%) Control group 95.35±2.091 Model Group <![CDATA[18.1±2.828 ### ]]> Model+drug group <![CDATA[75.99±2.843 *** ]]>

[0049] Note: ### P<0.001vs. control group; *** P<0.001vs. model group

[0050] Example 4: Effects of different concentrations of Rg1 on α-synuclein aggregation in SH-SY5Y-αSyn A53T cells treated with CORT

[0051] Experimental materials: The SH-SY5Y-αSyn A53T-mCherry stable overexpression cell line was constructed by the inventors, corticosterone (CORT) was purchased from Sigma-Aldrich, and Rg1 was purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0052] Experimental groups: control group, CORT model group, CORT+Rg1 0.1μM group, CORT+Rg1 1μM group, CORT+Rg110μM group, the cell independent experiment was repeated 4 times, n=4.

[0053] CORT modeling: SH-SY5Y-αSyn A53T-mCherry cells were grown at 10 5 pcs.cm -3 The cells were seeded at a density of 10 μM corticosterone (CORT) and different concentrations of Rg1 (0.1 μM, 1 μM, and 10 μM) on the bottom of a 24-well plate. After 24 hours of cell seeding, thioflavin S staining was performed for 48 hours.

[0054] Thioflavin S (ThS) staining: The cells on the slides were fixed with 4% paraformaldehyde at room temperature for 10 min, added with 5‰ TritonX-100 PBS solution at room temperature for 20 min, incubated with 0.1% Thioflavin S for 10 min, and then moved into 70% alcohol for differentiation for 5 min. The slides were washed with PBS and sealed. αSyn and ThS-positive inclusion bodies were observed under a fluorescence microscope, and the percentage of cells without double-positive inclusion bodies was counted (the number of cells without αSyn and ThS-positive inclusion bodies / the total number of cells in each field of view × 100%).

[0055] Statistics and analysis: All data are The data were analyzed statistically using one-way analysis of variance (Prism 8.0), Dunnett's test was used as a post hoc test, and P < 0.05 was set as the standard of statistical significance.

[0056] Results: As shown in Table 4 and Figure 5 The results of the effects of different concentrations of Rg1 on the aggregation of αSyn in CORT-treated SH-SY5Y-αSyn A53T-mCherry cells showed that compared with the control group, the proportion of cells without ThS-positive inclusion bodies in the model group was significantly reduced (16.09%±6.921%, P<0.001). Compared with the model group, 1μM and 10μM Rg1 could significantly increase the proportion of cells without ThS-positive inclusion bodies (35.56%±14.39%, P<0.01; 61.6%±0.7473%, P<0.001), indicating that Rg1 can significantly reduce the aggregation of α-synuclein induced by increased hormone levels.

[0057] Table 4 Effects of Rg1 on αSyn aggregation in PD model mice with aggravated emotional stress and gene interaction

[0058] Group Number of cells without ThS (%) Control group 72.02±4.249 CORT model group <![CDATA[16.09±6.921 ### ]]> CORT+Rg1 0.1μM group 20.64±3.354 CORT+Rg1 1μM group <![CDATA[35.56±14.39 ** ]]> CORT+Rg1 10μM group <![CDATA[61.6±0.7473 *** ]]>

[0059] Note:### P<0.001vs. control group; ** P<0.01, *** P<0.001vs. model group

[0060] In summary, the present invention tests Parkinson's related behaviors and pathologies through PD model mice with aggravated emotional stress and gene interaction, and detects α-synuclein aggregates at the animal and cell levels, and finds that compound Rg1 can improve the common movement coordination of Parkinson's patients in the model, improve bradykinesia and balance ability, and increase limb grasping ability. Rg1 can significantly increase the content of dopaminergic neurons and their fibers in the substantia nigra and striatum induced by emotional stress and gene interaction; and significantly reduce the model-induced α-synuclein aggregation.

[0061] Therefore, compound Rg1 provides an effective solution for the prevention and treatment of Parkinson's syndrome aggravated by emotional stress and alpha synuclein disease caused by emotional stress. Compound Rg1 is used as an active substance, used alone or / with other pharmacologically active compounds and / or extracts to form a compound, and various dosage forms of anti-Parkinson's syndrome and alpha synuclein disease aggravated by emotional stress are prepared according to conventional preparation methods in the pharmaceutical field, or compound preparations are prepared with other drugs to reduce adverse reactions in drug action while maintaining the therapeutic effect, which can provide an effective solution for the prevention and treatment of Parkinson's syndrome and alpha synuclein disease aggravated by emotional stress.

[0062] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the scope of protection of the invention.

Claims

1. Use of the compound Rg1 as shown in formula I in the preparation of drugs for preventing or treating Parkinson's syndrome and α-synuclein-related diseases aggravated by emotional stress:

2. The use according to claim 1, It is characterized in that The emotional stress can be caused by social environment, natural environment, competitive pressure, and long-term chronic diseases.

3. The use according to claim 1, It is characterized in that The Parkinson's syndrome includes primary Parkinson's syndrome, i.e. Parkinson's disease, symptomatic Parkinson's syndrome, hereditary degenerative Parkinson's syndrome and Parkinson's plus syndrome.

4. The use according to claim 1, It is characterized in that The α-synuclein-related diseases include Parkinson's disease, multiple system atrophy, and Lewy body dementia.

5. The use according to claim 3, It is characterized in that The secondary Parkinson's syndrome includes the clinical manifestations of the same symptoms as Parkinson's disease due to encephalitis, cerebrovascular disease, nervous system tumors, poisons, and drugs.

6. The use according to claim 5, It is characterized in that The clinical symptoms that are the same as those of Parkinson's disease include Parkinson-like motor symptoms and non-motor symptoms.

7. The use according to claim 6, It is characterized in that The Parkinson's-like motor symptoms include resting tremor, muscle rigidity and bradykinesia, and balance disorders; the non-motor symptoms include abnormal smell, mood changes, and cognitive disorders.

8. The use according to any one of claims 1 to 7, It is characterized in that The medicine or pharmaceutical composition comprises the compound Rg1 according to claim 1.

9. Use of a pharmaceutical composition in the preparation of a drug for preventing or treating Parkinson's syndrome aggravated by emotional stress and α-synuclein-related diseases, the pharmaceutical composition comprising a compound Rg1 as shown in formula I and a pharmaceutically acceptable carrier or excipient;

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