Composition and application thereof in treating neurodegenerative diseases

Abstract

The invention discloses a composition which is composed of notoginsenoside Rg1 and gastrodin, the composition is applied to preparation of drugs for treating neurodegenerative diseases, and experimental results show that the composition can significantly improve MPTP-induced zebrafish dyskinesia and brain tissue structure damage, shows a synergistic neuroprotective effect, and can be used for treating neurodegenerative diseases. The composition provided by the invention provides a new effective means for treatment of neurodegenerative diseases, and has important clinical application value and wide development prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a composition of notoginsenoside Rg1 and gastrodin and its use in treating neurodegenerative diseases. Background Art

[0002] Neurodegenerative diseases are chronic disorders characterized by the progressive degeneration and death of nerve cells. Their pathological hallmarks include abnormal protein aggregation (such as α-synuclein and β-amyloid), mitochondrial dysfunction, and oxidative stress imbalances. The incidence of these diseases, exemplified by Parkinson's disease (PD) and Alzheimer's disease (AD), continues to rise due to the increasing global aging population. According to the World Health Organization, PD patients exceed 10 million, and AD patients exceed 50 million. Their high disability rates and lack of a cure have posed a major public health challenge. Current clinical treatment strategies are primarily symptom-based, with dopamine replacement therapy such as levodopa (L-DOPA) used for PD and cholinesterase inhibitors (such as donepezil) or NMDA receptor antagonists (such as memantine) used for AD. However, these drugs can only improve cognitive or motor function in the short term and cannot slow disease progression. Long-term use can easily lead to drug tolerance, dyskinesia, or gastrointestinal side effects. Therefore, exploring new therapeutic strategies with multi-target regulation capabilities and low toxicity, especially synergistic interventions based on natural products, has become a current research focus.

[0003] In recent years, botanical active ingredients have demonstrated unique potential in the field of neuroprotection. Ginsenoside Rg1, a triterpenoid saponin isolated from the traditional Chinese medicinal herb Panax notoginseng, exhibits antioxidant, anti-apoptotic, and neurotransmitter-regulating properties. Gastrodin, the core active ingredient of the orchid Gastrodia elata, effectively penetrates the blood-brain barrier and exhibits sedative, anti-inflammatory, and neurorepair-promoting effects. While the neuroprotective effects of Rg1 and gastrodin alone have been gradually revealed, the synergistic mechanisms and therapeutic advantages of their combined use remain unclear. How to achieve a "1+1>2" synergistic effect through ingredient combinations remains an urgent scientific challenge. Summary of the Invention

[0004] The present invention provides a composition composed of notoginsenoside Rg1 and gastrodin. The present invention verifies the synergistic ability of the composition through an in vivo model, and effectively alleviates the symptoms of neurodegenerative diseases through a synergistic mechanism, improves motor dysfunction, nerve structure damage, and inflammation-related behavioral disorders, providing a new idea for developing highly effective and low-toxic treatment strategies for neurodegenerative diseases.

[0005] The molar ratio of the notoginsenoside Rg1 to gastrodin is 1:1.

[0006] The ingredients (or active ingredients) of the drug for treating neurodegenerative diseases in the present invention are notoginsenoside Rg1 and gastrodin, and one or more pharmaceutically acceptable excipients can also be added, or it can be compounded with other active ingredients to play a therapeutic role; in addition to being made into tablets, the drug can also be made into various pharmaceutically acceptable forms such as pills, powders, capsules, granules, oral liquids, and injections.

[0007] Advantages and technical effects of the present invention: The composition of the present invention achieves a therapeutic effect by improving neurobehavioral performance, reducing pathological damage to the brain tissue, and alleviating inflammation. In animal experiments, the composition significantly improves MPTP-induced movement disorders and brain tissue structure damage in zebrafish, showing a synergistic neuroprotective effect; the composition of the present invention is applicable to the treatment of Parkinson's disease, Alzheimer's disease, Huntington's disease, or other diseases characterized by neuronal degeneration, and has good safety. Description of the Drawings

[0008] Figure 1 It is a movement trajectory diagram of zebrafish in different experimental groups; Figure 2 It is a quantification diagram of the swimming distance of zebrafish in different experimental groups. In the figure, # represents comparison with the control group, * represents comparison with the model group, ##p < 0.01, ***p < 0.001, ****p < 0.0001; Figure 3 It is a quantification diagram of the average speed of zebrafish in different experimental groups; Figure 4 It is the result of observing the nerve structure changes by Nissl staining of zebrafish brain tissue in different experimental groups. Detailed Embodiments

[0009] The present invention will be further described below in conjunction with embodiments. However, the scope of the present invention is not limited to the following examples. Those skilled in the art can understand that various changes and modifications can be made to the present invention without departing from the spirit and scope of the present invention. The instruments, reagents, and materials involved in the following embodiments are all conventional instruments, reagents, and materials already existing in the prior art, and can be obtained through regular commercial channels without special instructions. The experimental methods, detection methods, etc. involved in the following examples are all conventional experimental methods and detection methods already existing in the prior art without special instructions.

[0010] Example 1: Establishment and Intervention of Zebrafish Parkinson's Disease Model Select 1-day-old wild-type AB strain zebrafish larvae. Under standard breeding conditions (water temperature 28.5 °C, 14h / 10h light-dark cycle, density ≤ 20 tails / well), randomly divide the zebrafish into five groups (n = 20 / group) and raise them in 6-well plates (each well capacity 4 mL). Blank control group: Normal culture without intervention; Model control group: Continuously expose to 50 μmol / L 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) solution for 5 days (change the drug solution regularly every day), construct a Parkinson's disease model and only treat without drug administration. Rg1 single drug group: MPTP treatment + 100 μmol / L notoginsenoside Rg1 immersion administration (24 h); Gastrodin single drug group: MPTP treatment + 100 μmol / L gastrodin immersion administration (24 h); Combined drug group: MPTP treatment + 50 μmol / L Rg1 and 50 μmol / L gastrodin combined drug solution.

[0011] Behavioral analysis: Under standard experimental conditions (water temperature 28 ± 0.5 °C, light intensity 300 lux), place the zebrafish in different treatment groups (n = 20 per group) individually in a behavioral test plate (diameter 10 mm) to adapt for 10 minutes, then shoot the swimming video of the zebrafish, and use the ANY-maze® video tracking system (v7.4) to analyze its 30-minute free swimming trajectory. Extract kinematic parameters through the built-in algorithm, including total moving distance, average speed, and the results of the swimming trajectory are shown in Figure 1 , and the results in the figure show that the blank control group presents a wide and dense movement path, indicating its active autonomous swimming; the movement trajectory of the model control group is significantly shortened and the distribution range is reduced, suggesting impaired motor function; the trajectory complexity and coverage range of the Rg1 or gastrodin single drug group are partially restored compared with the model group, while the motor ability of the combined drug group is significantly restored, the trajectory range is expanded, the movement frequency is increased, and its movement trajectory is close to the blank group level, suggesting that the two have a synergistic effect on improving neurobehavior.

[0012] The quantitative analysis results of the swimming behavior parameters of zebrafish in different treatment groups are shown in Figure 2 、 3, The data are expressed as mean ± SEM (n = 20 tails / group), and the statistical method is one-way ANOVA combined with Tukey's multiple comparison test; it can be seen from the figure that compared with the blank control group, the swimming distance of zebrafish in the model control group was significantly reduced due to the modeling treatment. The swimming distance of the gastrodin single-drug group and the Rg1 single-drug group was significantly restored compared with the model control group, and the combined drug group had the best restoration effect. The line graph of average speed further verified the above trend: the blank control group maintained stable high-speed movement, the speed of the model control group decreased significantly, and the speed recovery degree of each drug administration group was consistent with the swimming distance. Among them, the average speed of the combined drug group was close to the normal level.

[0013] Nissl staining of brain tissue: The brain tissues of zebrafish in each group were collected and Nissl staining (using toluidine blue method) was performed to observe the changes in nerve structure; the results are shown in Figure 4 , it can be seen from the figure that the neurons in the brain tissue of the blank control group were arranged closely, the Nissl bodies staining (dark blue granules) was uniform and abundant, the cell morphology was complete, and there was no vacuolar degeneration; due to the modeling treatment, the brain tissue of the model control group had significant pathological damage, manifested as extensive vacuolar degeneration, decreased neuron density and reduced number of Nissl bodies; the Rg1 single-drug group and the gastrodin single-drug group were improved; the neuron structure in the combined drug group was significantly restored, the vacuolar area was significantly reduced, the tissue was arranged closely, and the neuron density and Nissl bodies staining intensity were greatly restored compared with the model group, approaching the level of the blank control group.

Claims

1. A composition, characterized in that: It is composed of notoginsenoside Rg1 and gastrodin.

2. The composition according to claim 1, characterized in that: The molar ratio of notoginsenoside Rg1 to gastrodin is 1:

1.

3. Use of the composition according to claim 1 or 2 in the preparation of a medicament for treating neurodegenerative diseases.

4. The application according to claim 3, wherein: The neurodegenerative diseases are Parkinson's disease, Alzheimer's disease, and Huntington's disease.

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