Application of lignan B in preparation of medicine for preventing and / or treating neurodegenerative diseases or neurological diseases

Abstract

The invention discloses an application of lignan B in preparation of a medicine for preventing and / or treating neurodegenerative diseases or neurological diseases. In-vitro cell experiments and animal model researches find that the Licarin B can significantly reduce the expression level of ABAD or inhibit the enzymatic activity of ABAD, so that the nerve cell activity is improved, neuroinflammation is reduced, the epileptic seizure frequency is reduced, and the cognitive function is improved. The invention provides the new application of the Licarin B in preparing the medicine for preventing or treating the neurodegenerative diseases and the epilepsy for the first time, and a new way and means are developed for preventing and treating the neurodegenerative diseases and the epilepsy.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to the application of costenin B in the preparation of drugs for the prevention and / or treatment of neurodegenerative diseases or neurological diseases. Background Technology

[0002] Neurodegenerative diseases are a group of chronic and progressive central nervous system disorders characterized by the impairment and apoptosis of specific neurons, ultimately leading to cognitive, motor, and emotional dysfunction. Typical examples of neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and Huntington's disease (HD). Numerous studies have confirmed that the etiology of these diseases involves multiple pathological processes, such as abnormal aggregation of β-amyloid protein (Aβ), tau protein hyperphosphorylation, neurosteroid metabolism disorders, mitochondrial dysfunction, and persistent activation of inflammatory responses. Among these molecular mechanisms, the mitochondrial multifunctional enzyme 17β-hydroxysteroid dehydrogenase type 10 (ABAD) is considered a key target. ABAD is overexpressed in the brains of Alzheimer's patients and can directly bind to Aβ, further exacerbating mitochondrial damage and energy metabolism disorders. Studies have shown that inhibiting ABAD activity can reduce Aβ toxicity and improve neuronal survival; therefore, ABAD is considered an important candidate target for the prevention and treatment of neurodegenerative diseases.

[0003] Licarin B is a natural costanoid compound, mainly found in plants of the Lauraceae family and the Saussurea genus. Currently, there is no literature reporting a direct regulatory relationship between Licarin B and ABAD, nor is there any publicly available information on its application in the treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, or epilepsy. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides the application of costenin B in the preparation of drugs for the prevention and / or treatment of neurodegenerative diseases or neurological disorders, particularly for diseases such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and epilepsy, which are associated with abnormal expression of ABAD (17β-hydroxysteroid dehydrogenase type 10). This invention reveals for the first time that costenin B can negatively regulate ABAD and exhibits a role in improving pathological states in cell and animal models, providing new insights for the clinical translation of this compound.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: On the one hand, the present invention provides the use of costenin B in the preparation of medicaments for the prevention and / or treatment of neurodegenerative diseases or neurological disorders.

[0006] Preferably, the neurological disease is epilepsy.

[0007] Preferably, the neurodegenerative diseases include Alzheimer's disease, Huntington's disease, frontotemporal dementia, and Parkinson's disease.

[0008] In another aspect, the present invention provides the use of costenin B in the preparation of drugs that downregulate ABAD.

[0009] In another aspect, the present invention provides the application of costenin B in the preparation of ABAD enzyme inhibitors.

[0010] In the technical solution of the present invention, costenin B can downregulate the expression level of ABAD or inhibit the activity of ABAD enzyme, thereby improving nerve cell activity, reducing neuroinflammation, improving cognitive function, reducing the frequency of epileptic seizures and neuronal damage.

[0011] In another aspect, the present invention provides the use of costenin B in combination with a drug for improving cognitive impairment in the preparation of a drug for the prevention and / or treatment of neurodegenerative diseases or neurological diseases.

[0012] Preferably, the neurological disease is epilepsy.

[0013] Preferably, the neurodegenerative diseases include Alzheimer's disease, Huntington's disease, frontotemporal dementia, and Parkinson's disease.

[0014] Preferably, the drugs for improving cognitive impairment include donepezil, rivastigmine, galantamine, and memantine.

[0015] In another aspect, the present invention provides a pharmaceutical composition for the prevention and / or treatment of neurodegenerative diseases or neurological disorders, said pharmaceutical composition containing costenin B as an active ingredient and a pharmaceutically acceptable carrier.

[0016] In the technical solution of the present invention, the dosage form of the pharmaceutical composition is capsule, powder, tablet, granule, pill, injection, syrup, oral liquid, inhaler, ointment, suppository or patch.

[0017] This invention, through in vitro cell experiments and animal model studies, has found that Licarin B can significantly reduce the expression level of ABAD or inhibit its enzymatic activity, thereby enhancing nerve cell activity, reducing neuroinflammation, decreasing the frequency of epileptic seizures, and improving cognitive function. Further research shows that Licarin B can significantly reduce ABAD protein levels, improve cognitive impairment, and reduce the frequency of epileptic seizures in both in vitro and in vivo experiments, demonstrating good safety and application potential. This invention proposes for the first time a novel use of Licarin B in the preparation of drugs for the prevention or treatment of neurodegenerative diseases and epilepsy, opening up new avenues and methods for the prevention and treatment of these diseases.

[0018] Compared with the prior art, the present invention has the following outstanding advantages: 1. Novel mechanism of action: This invention discovers that costus extract B can intervene in the upstream pathological process of the disease by inhibiting the abnormal expression or activity of ABAD, thereby fundamentally improving mitochondrial dysfunction and energy metabolism disorders; 2. Naturally derived and highly safe: Costus root extract B is derived from natural plant components. Animal experiments have shown that long-term administration has not shown significant toxic side effects, indicating better prospects for clinical application. 3. Multiple pharmacological effects: In addition to ABAD regulation, this compound also has antioxidant, anti-inflammatory and neuroprotective effects, which can synergistically improve the neurodegenerative environment in multiple dimensions; 4. Sufficient experimental validation: Costus oleracea extract B showed the ability to reduce ABAD in cell models and significantly improved learning, memory and motor function in AD mouse models, proving its effectiveness and feasibility. Attached Figure Description

[0019] Figure 1 The study investigated the effect of 10 μM aβ1-42 on ABAD expression levels in a PC12 cell neurotoxicity model in vitro, showing that the costanone B treatment group had an inhibitory effect compared to the model group.

[0020] Figure 2 In in vitro cell experiments, the effects of different concentrations of costenin B on the ABAD expression level of 293T cells overexpressing ABAD were investigated, showing that the costenin B treatment group had an inhibitory effect compared with the model group.

[0021] Figure 3 The study investigated the toxic effects of different concentrations of costenin B on PC12 cells in in vitro cell experiments, showing that no significant cytotoxic side effects were observed within the effective dose range of costenin B.

[0022] Figure 4 A comparison of escape latency in Alzheimer's disease model mice administered costanol B via gavage in the water maze test, showing a significant difference between the costanol B treatment group and the model group.

[0023] Figure 5 A comparison of the time spent in the target quadrant of Alzheimer's disease model mice after oral administration of costanol B shows a significant difference between the costanol B treatment group and the model group.

[0024] Figure 6 The expression level of ABAD protein in the brain tissue of Alzheimer's disease model mice administered with costus extract B by gavage shows a significant difference between the costus extract B treatment group and the model group. Detailed Implementation

[0025] The following embodiments are merely some, not all, of the embodiments of the present invention. Therefore, the detailed descriptions of the embodiments provided below are not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0026] In this invention, unless otherwise specified, all equipment and raw materials are commercially available or commonly used in the industry. The methods described in the following embodiments are conventional methods in the art, unless otherwise specified.

[0027] Example 1: In the logarithmic growth phase of PC12 cells, a nerve injury model was established by treating them with Aβ1-42 (10 μM) for 12 hours. Two hours before treatment, 2.5 μM and 5 μM costenin B were added for pre-intervention. Subsequently, proteins were extracted and analyzed by Western blot. The results showed that costenin B could inhibit the increase of ABAD (…). Figure 1 ).

[0028] Example 2: 293T cells were transfected with a vector containing an ABAD overexpression plasmid, and stable expression lines were obtained. Subsequently, the cells were treated with 2.5 μM and 5 μM costenin B for 12 hours, respectively. Western blot analysis showed that costenin B significantly reduced ABAD protein levels compared to the model group. Figure 2 ).

[0029] Example 3: PC12 cells were seeded into 96-well plates. After stabilization, 0.01, 0.1, 1, 10, and 100 μM of costenin B were added and incubated for 48 hours. After discarding the culture medium, 10 μL of CCK-8 reagent was added to each well, and incubation continued for 2 hours. The absorbance was measured at 450 nm, and the viability was calculated. The results showed that the IC50 exceeded 100 μM, and no significant cytotoxicity was observed. Figure 3 ).

[0030] Example 4: Six-month-old male C57BL / 6J mice were selected as the control group, and APP / PS1 double transgenic mice were selected as the Alzheimer's disease model group. Low-dose (0.5 mg / kg) and high-dose (2.5 mg / kg) costanol B gavage groups were also included. The mice were administered the drug for 14 consecutive days, and the Morris water maze test was performed on days 9 to 14. During the training phase, the latency to find the platform was observed; in the exploration phase, the mice were placed in the maze and their movement trajectory was observed for 1 minute. The results showed that the drug-treated groups had a significantly shorter escape latency and a longer time spent in the target quadrant. Figure 4-5 This suggests improved learning and memory abilities. Further Western blot analysis showed a decrease in ABAD levels in brain tissue. Figure 6 ).

[0031] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The use of costenin B in the preparation of drugs for the prevention and / or treatment of neurodegenerative diseases or neurological disorders.

2. The application according to claim 1, characterized in that, The neurological disease is epilepsy; Preferably, the neurodegenerative diseases include Alzheimer's disease, Huntington's disease, frontotemporal dementia, and Parkinson's disease.

3. Application of costenin B in the preparation of drugs that downregulate ABAD.

4. Application of costenin B in the preparation of ABAD enzyme inhibitors.

5. The use of valerin B in combination with drugs that improve cognitive impairment in the preparation of drugs for the prevention and / or treatment of neurodegenerative diseases or neurological disorders.

6. The application according to claim 5, characterized in that, The neurological disorder is epilepsy.

7. The application according to claim 5, characterized in that, The neurodegenerative diseases mentioned include Alzheimer's disease, Huntington's disease, frontotemporal dementia, and Parkinson's disease.

8. The application according to claim 5, characterized in that, The medications mentioned for improving cognitive impairment include donepezil, rivastigmine, galantamine, and memantine.

9. A pharmaceutical composition for the prevention and / or treatment of neurodegenerative diseases or neurological disorders, characterized in that, The pharmaceutical composition contains costenol B as the active ingredient and a pharmaceutically acceptable carrier.

10. The pharmaceutical composition according to claim 9, characterized in that, The dosage form of the pharmaceutical composition is capsule, powder, tablet, granule, pill, injection, syrup, oral liquid, inhaler, ointment, suppository or patch.

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