Application of acacetin in preparation of medicine for treating autoimmune demyelination disease

Abstract

The invention belongs to the technical field of medicines, and discloses acacetin as shown in a formula (I) and application of pharmacodynamically acceptable salts thereof in preparation of drugs for preventing, relieving and / or treating autoimmune demyelination diseases. On a mouse experimental autoimmune encephalomyelitis model, acacetin shows a good treatment effect, and can effectively prevent and treat pathological changes and disease progression, relieve disease severity and inhibit LPS-stimulated microglial BV2 cells from releasing an inflammatory mediator, thereby providing a new drug and a new structure for clinical treatment.

Description

TECHNICAL FIELD

[0001] The application relates to the use of farnesol and / or a pharmaceutically acceptable salt thereof in the preparation of a drug for preventing, alleviating and / or treating an autoimmune demyelinating disease, and belongs to the technical field of medicines. BACKGROUND

[0002] Multiple sclerosis (MS) is a chronic and progressive inflammatory demyelinating disease of the central nervous system (CNS) mediated by immunity. More than 2 million people worldwide are affected, which causes serious harm to human health and heavy economic burden to society. The pathogenesis of multiple sclerosis is complex, the cause is unknown, and it cannot be cured at present, so patients need long-term treatment. Multiple sclerosis is mainly characterized by inflammation and demyelination in the brain, spinal cord and optic nerve, and its clinical manifestations are wide-ranging, including muscle weakness, sensory impairment, cognitive dysfunction and fatigue. The cause of multiple sclerosis is not clear, and it may be related to multiple factors such as heredity, environment and infection. According to the clinical manifestations of patients, multiple sclerosis can be divided into four types: relapsing-remitting type, which is characterized by alternating relapse and remission without obvious progression; primary progressive type, which is characterized by continuous deterioration after onset; secondary progressive type, which is characterized by continuous deterioration after relapsing-remitting type; and progressive relapsing type, which is characterized by gradual progression after onset accompanied by relapse. At present, the drugs for clinical treatment are mainly for patients with relapsing-remitting type.

[0003] Multiple sclerosis is considered an autoimmune disease, mainly caused by the entry of autoreactive immune cells into the CNS through the blood brain barrier. Its early lesions are characterized by peripheral immune cell infiltration and blood brain barrier (BBB) leakage. The cell infiltration is mainly macrophages, followed by CD8 + T cells, CD4 + T cells, B cells and plasma cells are relatively less. The composition of T cells does not change with the development of the disease, but the relative proportion of B cells and plasma cells increases. Microglia and macrophages remain in a state of chronic activation throughout the disease process, forming patches of myelin and oligodendrocyte loss. With the progression of the disease, patients develop focal white matter lesions in the brain, and brain and spinal cord damage is not obvious, but brain atrophy is common, accompanied by ventricular enlargement. Astrocytes form multiple sclerosis glial scars in white matter lesions, and demyelination also occurs in the cerebral cortex, nuclei and gray matter of the spinal cord, but the demyelinated areas of the white matter can be partially repaired by myelin regeneration. In addition, the disease process not only affects myelin, but also causes axonal and neuronal degeneration, resulting in irreversible disability in patients.

[0004] Over the past two decades, as people's understanding of the pathogenesis of multiple sclerosis deepens, researchers have developed a variety of drugs targeting the special physiological pathways of the disease. Currently, drugs for treating multiple sclerosis are mainly divided into five categories: immunomodulators, hormones, monoclonal antibodies, interferons, and nerve repair agents. These drugs can alleviate disease progression, control patients' symptoms, but are ineffective in repairing damaged neurons and have no improvement effect on patients' functional disability, and long-term use has serious toxic side effects.

[0005] The experimental autoimmune encephalomyelitis (EAE) model is a classic animal model of multiple sclerosis, which is initiated by myelin-specific helper T cells in the brain, causing inflammatory infiltration of the central nervous system and demyelination. Its biochemical, immune and pathological characteristics are very similar to multiple sclerosis. In addition, rat and mouse EAE can also be used as an ideal animal model for studying experimental autoimmune encephalomyelitis, opticospinal encephalomyelitis and acute disseminated encephalomyelitis, and other autoimmune demyelinating diseases. It is similar to human demyelinating diseases in terms of clinical, pathological, immune and biochemical changes, and is widely used.

[0006] The molecular formula of the acacetin described in the application is C 16 H 12 O5, which is named 5,7-Dihydroxy-4'-methoxyflavone; 5,7-dihydroxy-2-(4-methoxyphenyl)-4-benzopyrone. So far, Chinese patent CN 117959277A (publication number) records the "use of acacetin in the treatment of Alzheimer's disease", in which acacetin has the effect of preventing and treating Alzheimer's disease; Chinese patent CN 115969839A (publication number) records "application of acacetin or water-soluble prodrug of acacetin in preparation of drugs for preventing and treating immune myocarditis", in which acacetin has the effect of treating and / or preventing human immune myocarditis; Chinese patent CN 115337300A (publication number) records "use of water-soluble prodrug of acacetin for effectively treating pulmonary arterial hypertension", in which acacetin and its water-soluble prodrug have the potential to be developed into drugs for clinically preventing and treating pulmonary arterial hypertension; However, there is no report on the direct or indirect effect of acacetin on autoimmune demyelinating diseases at home and abroad. Therefore, the present invention mainly relates to the preparation of acacetin drugs and drug combinations, and the application in the preparation of drugs for preventing, relieving and / or treating autoimmune demyelinating diseases in clinical practice. SUMMARY

[0007] The present application aims to solve the technical problem of providing an application of farnesol in the preparation of a drug for preventing, alleviating and / or treating an autoimmune demyelinating disease.

[0008] To solve the technical problem of the present application, the present application provides the following technical solution:

[0009] The first aspect of the technical solution of the present application is to provide an application of farnesol and a pharmaceutically acceptable salt thereof as shown in formula (I) in the preparation of a drug for preventing, alleviating and / or treating an autoimmune demyelinating disease,

[0010]

[0011] The autoimmune demyelinating disease includes but is not limited to demyelinating autoimmune diseases of the central nervous system (Central nervous system, CNS) such as multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis, leukoencephalitis and transverse myelitis; demyelinating autoimmune diseases affecting the peripheral nervous system such as acute inflammatory demyelinating polyneuropathy (AIDP; Guillain-Barre syndrome), chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, motor and sensory neuropathy (HMSN), hereditary sensorimotor neuropathy (HSMN), peroneal muscular atrophy, progressive neurogenic peroneal muscular atrophy (Charcot-Marie-Tooth Disease) and the like.

[0012] The multiple sclerosis includes relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive-relapsing multiple sclerosis.

[0013] An EAE model was established using female C57BL / 6J mice. The effects of farnesin on animal body weight and disease scores were examined. Limb strength and treatment outcomes were observed through suspension grading and suspension time experiments. H&E staining and LFB staining were used to detect the ameliorative effect of farnesin on inflammatory cell infiltration and demyelination in the spinal cord of the experimental animals. An LPS-induced microglia BV2 cell activation model was used to detect the effect of farnesin on LPS-induced BV2 cell inflammatory responses. Based on these findings, the role of farnesin in the preparation of drugs for the prevention, alleviation, and / or treatment of autoimmune demyelinating diseases was determined.

[0014] The second aspect of the present invention is to provide the use of a pharmaceutical composition in the preparation of drugs for the prevention, relief and / or treatment of autoimmune demyelinating diseases, characterized in that the pharmaceutical composition contains an effective dose of farnesin as shown in formula (I), and a pharmaceutical excipient.

[0015]

[0016] The pharmaceutical composition contains, in addition to farnesin as the active pharmaceutical ingredient, other active ingredients. The pharmaceutical composition includes the following dosage forms: solution, suspension, lyophilized powder for injection, emulsion, pills, capsules, powder, controlled release, sustained release formulations, and microparticle delivery systems. The pharmaceutical excipients include starch, dextrin, sodium polymethyl cellulose, magnesium stearate, and talc. The product is selected from pharmaceuticals and health products.

[0017] The present invention therefore also relates to the use of pharmaceutical compositions with farnesin as the active ingredient in the prevention, relief, and / or treatment of autoimmune demyelinating diseases. The pharmaceutical composition can be prepared according to methods known in the art. It can be formulated into any dosage form suitable for human or animal use by combining the compound with one or more pharmaceutically acceptable solid or liquid excipients and / or adjuvants.

[0018] The compounds of this invention or pharmaceutical compositions containing them can be administered in unit doses via enteral or non-enteric routes, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eye, lung and respiratory tract, skin, vagina, rectum, etc. The dosage form can be liquid, solid, or semi-solid. Liquid dosage forms can be solutions (including true solutions and colloidal solutions), emulsions (including O / W, W / O, and double emulsions), suspensions, injections (including aqueous injections, powder injections, and infusions), eye drops, nasal drops, lotions, and liniments, etc.; solid dosage forms can be tablets (including ordinary tablets, enteric-coated tablets, lozenges, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules, and enteric-coated capsules), granules, powders, microcapsules, droplets, suppositories, films, patches, aerosols, sprays, etc.; semi-solid dosage forms can be ointments, gels, pastes, etc. The compounds of this invention can be formulated into conventional formulations, as well as sustained-release formulations, controlled-release formulations, targeted formulations, and various microparticle delivery systems.

[0019] To formulate the compounds of the present invention into tablets, a wide variety of excipients known in the art can be used, including diluents, binders, wetting agents, disintegrants, lubricants, and flow aids. Diluents can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, dicalcium phosphate, calcium carbonate, etc.; wetting agents can be water, ethanol, isopropanol, etc.; binders can be starch paste, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic paste, gelatin paste, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.; disintegrants 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 sorbitol fatty acid ester, sodium dodecyl sulfonate, etc.; lubricants and flow aids can be talc, silica, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc. The tablets can be further formulated into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or bilayer and multilayer tablets. To formulate the drug delivery unit into capsules, the active ingredient, the compound of the present invention, can be mixed with a diluent and a disintegrant, and the mixture can be placed directly into hard or soft capsules. Alternatively, the active ingredient, the compound of the present invention, can be first formulated into granules or microspheres with a diluent, binder, and disintegrant, and then placed into hard or soft capsules. The various diluents, binders, wetting agents, disintegrants, and disintegrants used to prepare tablets of the compounds of the present invention can also be used to prepare capsules of the compounds of the present invention. To formulate the compounds of the present invention into injections, water, ethanol, isopropanol, propylene glycol, or mixtures thereof can be used as solvents, and appropriate amounts of commonly used solubilizers, cosolvents, pH adjusters, and osmotic pressure adjusters can be added. Solubilizers or co-solvents can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin, etc.; pH adjusters can be phosphates, acetates, hydrochloric acid, sodium hydroxide, etc.; osmotic pressure adjusters can be sodium chloride, mannitol, glucose, phosphates, acetates, etc. When preparing lyophilized powder injections, mannitol, glucose, etc., can also be added as supporting agents. Furthermore, if necessary, colorants, preservatives, flavorings, tasters, or other additives can be added to the pharmaceutical preparation. To achieve the intended therapeutic effect, the drug or pharmaceutical composition of the present invention can be administered using any known method of administration.

[0020] Beneficial technical effects

[0021] 1. The acacia extract of the present invention can prevent, alleviate and / or treat autoimmune demyelinating diseases, providing a new structural type of drug option for the clinical treatment of autoimmune demyelinating diseases.

[0022] 2. The acacia extract of this invention can achieve therapeutic and preventative effects with oral administration and small doses. The drug is safe and reliable. Its development as a medicine has significant advantages. Attached Figure Description

[0023] Figure 1 Effects of farnesin on body weight in EAE mice. In this experiment, the body weight of mice in the EAE model group was significantly lower than that of the normal control group after the onset of the disease. After administration, compared with the model group, the body weight of the farnesin treatment group increased significantly in the later stage of administration.

[0024] Figure 2 Effects of farnesin on disease scores in EAE mice. In this experiment, the disease scores of mice in the EAE model group were significantly higher than those in the normal control group after the onset of the disease. After administration of farnesin, the overall symptoms of mice in the farnesin-treated group were alleviated, and their disease scores were significantly lower than those in the EAE model group, showing a significant improvement effect on disease scores. This confirms that farnesin has a significant effect on improving the neurological function of EAE mice.

[0025] Figure 3 Effect of farnesin on suspension time in EAE mice. In this experiment, compared with the normal control group, the suspension time of EAE model mice on wire mesh was significantly reduced. Farnesin could prolong the suspension time of EAE mice, confirming that farnesin treatment has a significant effect on improving the motor function of EAE mice. ### P < 0.001 vs. normal control group, ***P < 0.001 vs. EAE model group.

[0026] Figure 4 Effects of farnesin on suspension grading in EAE mice. In this experiment, compared with the normal control group, the suspension scores of mice in the EAE model group were significantly reduced after the onset of the disease. After administration, the suspension scores of EAE mice in the farnesin-treated group were significantly increased compared with the EAE model group. ### P < 0.001 vs. normal control group, **P < 0.01, ***P < 0.001 vs. EAE model group.

[0027] Figure 5 Effects of farnesin on inflammatory cell infiltration in the spinal cord of EAE mice. In this experiment, compared with the normal control group, the spinal cord of EAE model mice showed significant inflammatory cell infiltration, while farnesin could significantly reduce the infiltration area of ​​inflammatory cells.

[0028] Figure 6 Effects of farnesin on demyelination of the spinal cord in EAE mice. In this experiment, after LFB staining, compared with the normal control group, the spinal cord of mice in the EAE model group showed demyelination lesions with a larger area. Farnesin could reduce the area of ​​white matter in the spinal cord, effectively improving the demyelination condition. Detailed Implementation

[0029] The following description, in conjunction with the present invention, further illustrates the pharmacological effects of farnesin and its pharmacodynamically acceptable salts in the prevention, alleviation, and / or treatment of autoimmune demyelinating diseases.

[0030] The following embodiments illustrate the invention in more detail, but are not intended to limit the invention in any way.

[0031] Example 1: The effect of farnesin on the behavioral improvement of EAE mice

[0032] 1.1 Establishment and drug administration of an experimental autoimmune encephalomyelitis mouse model

[0033] Experimental Principle

[0034] C57BL / 6J mice were treated with MOG 35-55 Induced EAE model.

[0035] Experimental methods

[0036] Female C57BL / 6J mice, 6 weeks old, weighing 16–18 g, were subcutaneously injected with MOG after 3–5 days of acclimatization feeding. 35-55 An experimental autoimmune encephalomyelitis (EAE) animal model was established by intravenous injection of 300 μg of pertussis toxin and 400 ng of pertussis toxin. A normal control group was also set up. Eleven days after modeling, the animals began to show symptoms, exhibiting varying degrees of limb paralysis, confirming the successful establishment of the mouse model of experimental autoimmune encephalomyelitis.

[0037] Female C57BL / 6 mice were randomly divided into two groups after immunization: an EAE model group and an EAE + 100 mg / kg farnesin administration group. Starting 14 days after modeling, the mice were administered the farnesin via gavage once daily. The normal control group and the EAE model group received the same volume of solvent control (0.5% sodium carboxymethyl cellulose solution). Farnesin administration continued until day 28 after immunization. Animal weight and disease scores were measured daily, and mortality was recorded. Suspension grading was measured on days 7, 14, 21, and 28 post-immunization, and the suspension time on the wire mesh was measured on day 28.

[0038] Experimental results

[0039] The animals began to show symptoms on day 11 after immunization, including weight loss and decreased neurological function scores.

[0040] 1.2 Effects of farnesin on body weight in EAE mice

[0041] Experimental methods

[0042] Body weight is an important indicator of an animal's energy balance and growth. In this experiment, we observed and recorded the animals' activity level, coat condition, and other general characteristics daily, and monitored their body weight daily.

[0043] Experimental results

[0044] In this experiment, the body weight of mice in the EAE model group was significantly lower than that of the normal group after the onset of the disease. However, compared with the model group, the body weight of mice in the acacia extract treatment group increased in the later stages of drug administration, confirming that acacia extract has an effect on improving weight loss. Results are shown below. Figure 1 1.3 Effects of acacia extract on disease scores in EAE mice

[0045] Experimental methods

[0046] After modeling, the experimental mice were scored daily using the following criteria:

[0047] 0 points: Normal mouse; 0.5 points: Tail weakness; 1 point: Complete tail paralysis; 1.5 points: One hind limb weakness; 2 points: Both hind limbs weakness; 2.5 points: One hind limb paralysis and the other hind limb weakness; 3 points: Both hind limbs paralysis; 3.5 points: Partial forelimb weakness; 4 points: Partial forelimb paralysis; 4.5 points: Complete forelimb paralysis; 5 points: Death.

[0048] Experimental results

[0049] In this experiment, the disease score of the EAE model group mice was significantly higher than that of the normal control group after the onset of the disease. After administration of the drug, the overall symptoms of the mice in the acacia extract group were alleviated, and the disease score was significantly lower than that of the EAE model group, showing a significant improvement effect on the disease score. This confirms that acacia extract has a significant improving effect on the neurological function of EAE mice. Results are shown below. Figure 2 .

[0050] 1.4 Effect of farnesin on suspension time in EAE mice

[0051] Experimental methods

[0052] On day 28 after modeling, the time it took for mice to fall from a 180° wire mesh was measured; a time greater than 120 seconds was counted as 120 seconds.

[0053] Experimental results

[0054] In this experiment, compared with the normal control group, the suspension time of EAE model mice on the wire mesh was significantly reduced. Acacia extract could prolong the suspension time of EAE mice, confirming that acacia extract treatment has a significant improving effect on the motor function of EAE mice. Results are shown below. Figure 3 And Table 1.

[0055] Table 1. Effects of acacia extract on suspension time in MOG-induced EAE mice.

[0056]

[0057] Mean±SEM (n=6).

[0058] ### P < 0.001 vs. normal control group, ***P < 0.001 vs. EAE model group.

[0059] 1.5 Effect of farnesin on suspension grading in EAE mice

[0060] Experimental methods

[0061] On days 7, 14, 21, and 28 after modeling, the mice's forepaws were suspended from a balance rope 30 cm above the ground. The suspension status of the mice's limbs on the balance rope was observed and scored. The grading criteria were as follows: 5 points: Grasping the rope and able to pull with the hind limbs, with the tail tightly wrapped around the rope; 4 points: Grasping the rope and able to pull with the hind limbs, with the tail raised but not wrapped around the rope; 3 points: Grasping the rope and able to pull with the hind limbs, with the tail drooping; 2 points: Raising the hind limbs and grasping the rope but unable to pull; 1 point: Raising the hind limbs but unable to grasp the rope; 0 points: Unable to raise the hind limbs.

[0062] Experimental results

[0063] In this experiment, compared with the normal control group, the suspension score of mice in the EAE model group was significantly reduced after the onset of the disease. After administration, compared with the EAE model group, the suspension score of EAE mice in the acacia extract administration group was significantly increased, confirming that acacia extract can significantly improve the suspension behavior of EAE mice. Results are shown below. Figure 4 And Table 2.

[0064] Table 2. Effects of acacia extract on suspension grading in MOG-induced EAE mice.

[0065]

[0066] Mean±SEM (n=6).

[0067] ### P < 0.001 vs. normal control group; **P < 0.01, ***P < 0.001 vs. EAE model group.

[0068] Example 2: Effects of farnesin on inflammatory cell infiltration and demyelination of the spinal cord in EAE model mice

[0069] 2.1 Establishment of the EAE mouse model and drug administration

[0070] The experimental principle, experimental method, and experimental results are the same as in Example 1.1.

[0071] 2.2 Effects of farnesin on inflammatory cell infiltration in the spinal cord of EAE mice

[0072] Experimental methods

[0073] On day 28 after modeling, three mice from each group were anesthetized with 4% tribromoethanol. The mice were first perfused with physiological saline until the liver turned white, then perfused with 4% paraformaldehyde until the limbs stiffened. The mice were then decapitated, and the lumbar enlarged portion of the spinal cord was fixed in 4% paraformaldehyde. Paraffin sections of the lumbar enlarged portion of the spinal cord were prepared and stained with hematoxylin and eosin (H&E) to observe the infiltration of inflammatory cells in the spinal cord.

[0074] Experimental results

[0075] In this experiment, compared with the normal control group, the EAE model group mice showed significant infiltration of inflammatory cells in the spinal cord. Treatment with 100 mg / kg farnesin significantly inhibited the infiltration of inflammatory cells in the spinal cord of EAE mice, and the pathological changes such as fibrosis and vacuolation caused by inflammatory infiltration were significantly improved, confirming that farnesin can significantly improve inflammatory cell infiltration in the spinal cord of EAE mice. Results are shown below. Figure 5 .

[0076] 2.3 Effects of farnesin on demyelination in the spinal cord of EAE mice

[0077] Experimental methods

[0078] On day 28 after modeling, three mice from each group were anesthetized with 4% tribromoethanol. The mice were first perfused with physiological saline until the liver turned white, then perfused with 4% paraformaldehyde until the limbs stiffened. The mice were then decapitated, and the lumbar enlargement of the spinal cord was fixed in 4% paraformaldehyde. Paraffin sections of the lumbar enlargement of the spinal cord were prepared and stained with Fast Blue (LFB) to observe the demyelination within the spinal cord.

[0079] Experimental results

[0080] In this experiment, after LFB staining, compared with the normal control group, the spinal cord of EAE model mice showed demyelinating lesions with a larger area. 100 mg / kg farnesin could reduce the area of ​​white matter in the spinal cord of EAE mice, effectively improving the demyelination condition. Results are shown below. Figure 6 .

[0081] Example 3: The effect of farnesin on improving inflammation in LPS-induced microglia BV2 cells

[0082] 3.1 Establishment and drug administration of the LPS-induced BV2 cell inflammation model

[0083] Experimental methods

[0084] BV2 cells were cultured at 37°C, 5% CO2, and saturated humidity in DMEM high-glucose complete medium (Gibco) containing 10% fetal bovine serum (FBS). When the cells showed logarithmic growth, they were cultured at a rate of 2.5 × 10⁻⁶ cells / year. 4 Cells were seeded per well in 96-well plates, with 100 μL of cell suspension per well, and cultured overnight at 37°C in a 5% CO2 incubator. A normal control group, a model group, and a drug-treated group were set up. The supernatant was discarded and replaced with serum-free medium, 80 μL per well. Physiological saline containing DMSO was added to the normal control and model groups to bring the final DMSO concentration to 0.1%. The drug-treated group was incubated with a 10 μM concentration of farnesin. After 2 hours of incubation, LPS (Yuan Ye, S11060) was added to each well of the model and drug-treated groups to bring the final concentration to 1 μg / ml. After 24 hours of culture, 50 μL of the supernatant was collected to detect NO production, following the instructions of the NO detection kit (Pulley, E1030). (If the detection exceeds the upper limit of the standard curve or the microplate reader, the supernatant can be appropriately diluted before detection). After discarding the supernatant, cell viability was detected using the MTS method.

[0085] NO inhibition rate (%) = (NO 模型组 -NO 给药组 ) / (NO 模型组 -NO 对照组 )×100%

[0086] Experimental results:

[0087] The results are shown in Table 3.

[0088] Table 3. Inhibition rate of NO production and cell viability of LPS-stimulated BV2 cells by farnesin (n=4)

[0089]

Claims

1. The use of farnesin as shown in formula (I) and / or its pharmacodynamically acceptable salts in the preparation of medicaments for the prevention, relief and / or treatment of autoimmune demyelinating diseases; 2. The application according to claim 1, characterized in that, The autoimmune demyelinating diseases include demyelinating autoimmune diseases of the central nervous system and demyelinating autoimmune diseases affecting the peripheral nervous system.

3. The application according to claim 2, characterized in that, The aforementioned demyelinating autoimmune diseases of the central nervous system include multiple sclerosis, neuromyelitis optica spectrum disorders, acute disseminated encephalomyelitis, leukoencephalitis, and transverse myelitis. Demyelinating autoimmune diseases affecting the peripheral nervous system include acute inflammatory demyelinating polyneuropathy, chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, motor and sensory neuropathy, genetic sensorimotor neuropathy, peroneal muscular atrophy, and progressive neurogenic peroneal muscular atrophy.

4. The application according to claim 3, characterized in that, The multiple sclerosis includes relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis, and progressive-relapsing multiple sclerosis.

5. The use of a pharmaceutical composition in the prevention, relief, and / or treatment of autoimmune demyelinating diseases, characterized in that, The pharmaceutical composition contains an effective dose of farnesin as shown in formula (I), and optionally a pharmaceutically acceptable excipient.

6. The application according to claim 5, characterized in that, In addition to farnesin and / or its pharmaceutically acceptable salts as active pharmaceutical ingredients, the pharmaceutical composition contains other active ingredients.

7. The application according to any one of claims 5-6, characterized in that, The pharmaceutical compositions include the following dosage forms: solutions, suspensions, lyophilized powder for injection, emulsions, pills, capsules, powders, controlled-release, sustained-release formulations, and microparticle delivery systems.

8. The application according to claim 5, characterized in that, The pharmaceutical excipients include starch, dextrin, sodium polymethyl cellulose, magnesium stearate, and talc.

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