CN116350620A - Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases - Google Patents

Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases Download PDF

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CN116350620A
CN116350620A CN202111625337.8A CN202111625337A CN116350620A CN 116350620 A CN116350620 A CN 116350620A CN 202111625337 A CN202111625337 A CN 202111625337A CN 116350620 A CN116350620 A CN 116350620A
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puerarin
multiple sclerosis
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杜冠华
李莉
赵佳莹
吕扬
谢逸菲
邢逞
申艳佳
陈姝含
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Abstract

The invention belongs to the technical field of medicines, and discloses application of puerarin in preparation of medicines for preventing, relieving and/or treating autoimmune demyelinating diseases. Puerarin shows a very good therapeutic effect on the experimental autoimmune encephalomyelitis model in mice, and can effectively treat pathological changes and disease progression of diseases. The therapeutic effect is achieved by reducing inflammatory cell infiltration of spinal cord and demyelination of spinal cord.

Description

Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases
Technical Field
The invention relates to application of puerarin in preparing a medicine for preventing, relieving and/or treating autoimmune demyelinating diseases, and belongs to the technical field of medicines.
Background
Multiple sclerosis (multiple sclerosis, MS) is a chronic progressive central nervous system (central nervous system, CNS) inflammatory demyelinating disease mediated by immunity. Over 200 tens of thousands of people are affected worldwide, which causes serious harm to human health and a heavy economic burden to society. Multiple sclerosis has a complex pathogenesis and unknown etiology, and is currently incurable, and patients need to receive long-term treatment. Multiple sclerosis is characterized by inflammation and demyelination of brain, spinal cord and optic nerve as major pathological features, and its clinical manifestations are extensive, including muscle weakness, sensory disturbance, cognitive dysfunction and fatigue. The etiology of multiple sclerosis is not clear and may be related to various factors such as genetics, environment, infection, etc. Multiple sclerosis can be divided into four types according to the clinical manifestations of the patient: the recurrence remission is expressed as alternation of recurrence remission, and the disease does not obviously progress; primary progression, i.e. progressive deterioration after onset; secondary progressive, onset with remission of recurrence followed by progressive worsening; the disease is gradually progressed with recurrence after the disease is developed. Currently, clinical therapeutic drugs are mostly aimed at relapsing remitting patients.
Multiple sclerosis is considered an autoimmune disease, mainly caused by the passage of autoreactive immune cells into the CNS through the blood brain barrier. Its early lesions are manifested by infiltration of surrounding immune cells and leakage of the blood brain barrier (blood brain barrier, BBB). Cell infiltration is mainly carried out by macrophages, CD8 + T cell subset, CD4 + T cells, B cells and plasma cells are relatively small in number. The composition of T cells does not change with the progression of the disease, but B cells and plasma cellsThe relative proportion of (2) increases. Microglia and macrophages remain chronically activated throughout the disease process, forming plaques of myelin and oligodendrocyte loss. With the progress of the disease, the brain of the patient has focal white matter lesions, brain and spinal cord injuries are not obvious, but brain atrophy is commonly generated, brain atrophy is accompanied by ventricle enlargement, astrocytes form multiple sclerosis colloid scars in white matter lesions, demyelination can also occur in the gray matter of cerebral cortex, nucleus and spinal cord, but demyelinated areas of white matter can be partially repaired through remyelination; in addition, the disease process affects not only myelin, but also causes degenerative changes in axons and neurons, resulting in irreversible disability in the patient.
Over the past two decades, as people have gained a continual understanding of the pathogenesis of multiple sclerosis, researchers have developed a variety of drugs that address the particular physiological pathways of the disease. Currently, drugs for treating multiple sclerosis are mainly divided into five major categories: immunomodulators, hormones, monoclonal antibodies, interferons and nerve repair agents. The medicines can relieve the disease progression and control the symptoms of patients, but are ineffective in repairing damaged neurons, have no improving effect on the functional disability of the patients, and have serious toxic and side effects after long-term application.
The experimental autoimmune encephalomyelitis (experimentally allergic encephalomyelitis, EAE) model is a classical animal model of multiple sclerosis, and the specific activation of brain helper T cells by myelin autoantigens causes inflammatory infiltration of the central nervous system, demyelination, and the biochemical, immunological and pathological features are very similar to those of multiple sclerosis. In addition, the EAE of rats and mice can be used as an ideal animal model for researching autoimmune demyelinating diseases such as experimental autoimmune encephalomyelitis, optic nerve encephalomyelitis, acute disseminated encephalomyelitis and the like, and is similar to human demyelinating diseases in clinical, pathological, immune, biochemical changes and the like, so that the EAE has wide application.
Pueraria Lobata (Pueraria Lobata) is a dry root of Pueraria Lobata (Pueraria Lobata) of Leguminosae, is a commonly used traditional Chinese medicine, has sweet, pungent and cool nature, and has effects of invigorating spleen and stomach, relieving fever, promoting salivation, quenching thirst, and invigorating yang to arrest diarrhea.
Puerarin (Puerarin) is isoflavone derivative separated from radix Puerariae with crown expanding effect. Is prepared from root of Pueraria lobata Ohwi of Leguminosae. Research by scholars at home and abroad shows that the isoflavone compound has obvious effects in preventing and treating cardiovascular and cerebrovascular diseases, diabetes and the like, such as dilating coronary artery and improving ischemic myocardial metabolism; protecting against cerebral arterial ischemia and ischemia reperfusion injury; lowering blood pressure and dilating blood vessels; lowering blood viscosity, slowing heart rate, and reducing myocardial oxygen consumption; reducing blood sugar and blood lipid, scavenging free radicals and resisting lipid peroxidation; anti-atherosclerosis, improving brain circulation, inhibiting platelet aggregation, etc.; in addition, puerarin has obvious effect on preventing and treating middle-aged and senile osteoporosis, female climacteric syndrome, etc. Modern scientific researches also find that puerarin has various pharmacological effects of protecting liver, regulating immunity, resisting tumor, protecting cardiovascular and cerebrovascular, reducing blood sugar, resisting oxidation, reducing blood sugar, reducing blood lipid, reducing blood pressure, resisting inflammation, improving renal function, increasing bone density, protecting nerve, etc. Is clinically used for treating coronary heart disease, angina, hypertension and the like.
The invention is a new discovery obtained through a great number of animal experimental researches. The novel invention relates to a medicine for treating autoimmune demyelinating diseases. At present, no report is available on the direct or indirect treatment effect of puerarin on autoimmune demyelinating diseases.
To date, a number of patents relate to the use of puerarin. The application of puerarin gel eye drops in preparing medicines for treating ocular fundus ischemic diseases is described in Chinese patent CN 104688672A (publication number). Wherein, the gel eye drop formulation of puerarin can be used as intravenous injection puerarin for treating ocular fundus ischemic diseases. Chinese patent CN 101550133A (publication No.) describes "extraction method of puerarin and use of radix Puerariae in preparation of liver protecting medicine". Animal experiments prove that puerarin has good effects of detoxification and liver protection and can be used as a liver protection medicament. The use of puerarin in the preparation of analgesic drugs is described in chinese patent CN 104940190a (publication No.). The puerarin is used in combination with opioid or compound preparation with opioid, which can prolong the analgesic time, enhance the analgesic effect, and delay or relieve opioid tolerance phenomenon in the treatment course of chronic opioid. Chinese patent No. CN 103520147A (publication No.) describes the use of puerarin or a pharmaceutical composition containing puerarin in the preparation of a medicament for preventing or treating Alzheimer's disease. The pharmaceutical composition comprising puerarin, triptolide, galanthamine and borneol is used for treating senile dementia, so that the toxic and side effects of the medicine can be reduced, and the synergistic treatment effect can be achieved. Puerarin can obviously inhibit the deposition of beta amyloid, has definite curative effect for preventing or treating senile dementia, small side effect and wide medical application prospect. In addition, the pharmacological effects of puerarin are proved from various aspects by the patents such as the application of puerarin in preparing medicines for treating endometriosis (CN 1899295A), the application of puerarin in preparing medicines for treating P2X3 mediated pain/nervous system diseases (CN 101627990A), the application of puerarin and puerarin in preparing medicines for preventing and treating osteoporosis (CN 1321500A), the protective effect of puerarin in TBBPA induced cardiodevelopmental toxicity (CN 103432113A), the application of puerarin in preparing medicines for preventing and/or treating pulmonary arterial hypertension and complications thereof (CN 108567769A) and the like. However, the above studies on the effects of puerarin have not been reported on the treatment of autoimmune demyelinating diseases. Therefore, the application of puerarin in preparing the medicine for preventing, relieving and/or treating autoimmune demyelinating diseases is a new application of the puerarin newly discovered.
Disclosure of Invention
The invention aims to solve the technical problem of providing application of puerarin in preparing a medicine for preventing, relieving and/or treating autoimmune demyelinating diseases.
In order to solve the technical problems of the invention, the invention provides the following technical scheme:
in a first aspect, the invention provides an application of puerarin shown in a formula (I) in preparing a medicament for preventing, relieving and/or treating autoimmune demyelinating diseases,
Figure BDA0003438676800000031
such autoimmune demyelinating diseases include, but are not limited to, demyelinating autoimmune diseases of the central nervous system (Central nervous system, CNS) such as multiple sclerosis, neuromyelitis optica (Neuromyelitis optica spectrum disorder, NMOSD), acute disseminated encephalomyelitis, white matter encephalitis and transverse myelitis; demyelinating autoimmune diseases affecting the peripheral nervous system such as acute inflammatory demyelinating polyneuropathy (acute inflammatory demyelinating polyneuropathy, AIDP; guillain-Barre syndrome), chronic inflammatory demyelinating polyneuropathy (chronic inflammatory demyelinating polyneuropathy), anti-MAG peripheral neuropathy (anti-MAG peripheral neuropathy), motor and sensory neuropathy (Motor and Sensory Neuropathy, HMSN), hereditary sensorimotor neuropathy (Hereditary Sensorimotor Neuropathy, HSMN), fibular muscular atrophy (Peroneal Muscular Atrophy), progressive neurofibular muscular atrophy (Charcot-Marie-photon Disease), and the like.
The multiple sclerosis includes relapsing remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive relapsing multiple sclerosis.
An EAE model was established using female C57BL/6 mice. Detecting the influence of puerarin on animal weight and disease score; and observing the force of the limbs of the animal through a suspension experiment, and observing the treatment condition. The improvement effect of puerarin on inflammatory cell infiltration and myelination in the spinal cord of experimental animals is detected by using H & E staining and LFB staining, and the effect of puerarin in preparing the medicines for preventing, relieving and/or treating autoimmune demyelinating diseases is judged according to the improvement effect.
In a second aspect, the present invention provides an application of a pharmaceutical composition in preparing a medicament for preventing, alleviating and/or treating autoimmune demyelinating diseases, wherein the pharmaceutical composition comprises puerarin shown in formula (I) in an effective dose, and a pharmaceutical excipient,
Figure BDA0003438676800000041
wherein, the medicine composition contains puerarin as the medicine active ingredient and other active ingredients. The pharmaceutical composition comprises the following dosage forms: solutions, suspensions, lyophilized powders, emulsions, pills, capsules, powders, controlled release, sustained release formulations, and microsomal delivery systems. The medicinal excipient comprises starch, dextrin, sodium polymethyl cellulose, magnesium stearate and talcum powder. The product is selected from medicines and health products.
The invention also relates to the application of the pharmaceutical composition taking puerarin as an active ingredient in the medicines for preventing, relieving and/or treating autoimmune demyelinating diseases. The pharmaceutical compositions may be prepared according to methods well known in the art. Any dosage form suitable for human or animal use may be made by combining the compounds of the invention with one or more pharmaceutically acceptable solid or liquid excipients and/or adjuvants.
The compounds of the present invention or pharmaceutical compositions containing them may be administered in unit dosage form by the enteral or parenteral route, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosal, ocular, pulmonary and respiratory, cutaneous, vaginal, rectal, etc. The dosage form may be a liquid, solid or semi-solid dosage form. The liquid preparation can be solution (including true solution and colloid solution), emulsion (including o/w type, w/o type and multiple emulsion), suspension, injection (including injection solution, powder injection and transfusion), eye drop, nasal drop, lotion, liniment, etc.; the solid dosage forms can be tablets (including common tablets, enteric coated tablets, buccal tablets, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules (including hard capsules, soft capsules and enteric coated capsules), granules, powder, micropills, dripping pills, suppositories, films, patches, aerosol (powder) and sprays; the semisolid dosage form may be an ointment, gel, paste, or the like. The compound of the invention can be prepared into common preparations, slow release preparations, controlled release preparations, targeted preparations and various microparticle administration systems.
For the preparation of the compounds of the present invention into tablets, various excipients known in the art may be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, glidants. The diluent can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; the wetting agent can be water, ethanol, isopropanol, etc.; the binder may be starch slurry, dextrin, syrup, mel, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.; the disintegrating agent 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.; the lubricant and glidant may be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar coated tablets, film coated tablets, enteric coated tablets, or bilayer and multilayer tablets. In order to make the administration unit into a capsule, the compound of the present invention as an active ingredient may be mixed with a diluent, a glidant, and the mixture may be directly placed in a hard capsule or a soft capsule. The active ingredient of the compound can be prepared into particles or pellets by mixing with a diluent, an adhesive and a disintegrating agent, and then placed into hard capsules or soft capsules. The various diluents, binders, wetting agents, disintegrants and glidants used to prepare the tablets of the compounds of the invention may also be used to prepare capsules of the compounds of the invention. For the preparation of the compound of the present invention into injection, water, ethanol, isopropanol, propylene glycol or their mixture may be used as solvent, and appropriate amount of solubilizer, cosolvent, pH regulator and osmotic pressure regulator may be added. The solubilizer or cosolvent can be poloxamer, lecithin, hydroxypropyl-beta-cyclodextrin, etc.; the pH regulator can be phosphate, acetate, hydrochloric acid, sodium hydroxide, etc.; the osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate, etc. For example, mannitol, glucose, etc. can be added as propping agent for preparing lyophilized powder for injection. In addition, colorants, preservatives, fragrances, flavoring agents, or other additives may also be added to the pharmaceutical formulation, if desired. For the purpose of administration, the drug or the pharmaceutical composition of the present invention can be administered by any known administration method to enhance the therapeutic effect.
Beneficial technical effects
1. The compounds of the invention are useful in the prevention, alleviation and/or treatment of autoimmune demyelinating diseases. Besides widening the clinical application field of the compound, the compound also provides medicine selection for the clinical treatment of autoimmune demyelinating diseases.
2. The application of the compound in the medicine for preventing, relieving and/or treating autoimmune demyelinating diseases is disclosed for the first time at present in the world and in the country. See no related papers and patent publications.
3. The compound of the invention can achieve the therapeutic and preventive effects by gastric administration and a small amount of administration. The medicine is safe and reliable. The medicine has obvious advantages when being developed as a medicine.
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FIG. 1 effects of puerarin on EAE mice body weight. In this experiment, mice in the EAE model group had significantly lower body weight than normal control group after onset. And after the administration, compared with a model group, the body weight of the puerarin treatment group mice in the later administration period is obviously increased.
FIG. 2 effect of puerarin on EAE mouse disease score. In this experiment, the disease score of mice in the EAE model group after onset was significantly higher than that of mice in the normal control group, and the disease score of mice in the puerarin treatment group after administration was significantly lower than that of mice in the EAE model group.
FIG. 3 effect of puerarin on EAE mice suspension time. In this experiment, the suspension time on wire netting was significantly reduced in mice of EAE model group compared to normal control group, while puerarin can prolong the suspension time in model mice. # # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
FIG. 4 effect of puerarin on EAE mice suspension fractionation. # # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
FIG. 5 effect of puerarin on myelitis cell infiltration in EAE mice. In the experiment, compared with a normal control group, the EAE model group mice have obvious infiltration of spinal cord inflammatory cells, and puerarin can obviously reduce the infiltration area of inflammatory cells.
FIG. 6 effect of puerarin on demyelination of the spinal cord of EAE mice. In this experiment, after LFB staining, the spinal cord of mice in EAE model group exhibited demyelination lesions with larger area compared to normal control group. And puerarin can reduce the whitening area of the spinal cord white matter area, so that the demyelination situation is effectively improved. # P <0.01vs. normal control group, # P <0.01vs. eae model group.
Detailed Description
The pharmacological actions of puerarin in the prevention, alleviation and/or treatment of autoimmune demyelinating diseases are further described below in connection with the present invention.
The following examples illustrate the invention in more detail, without any limitation thereof.
Example 1: puerarin effect on improving behaviours of experimental autoimmune encephalomyelitis mice
1.1 establishment of an Experimental autoimmune encephalomyelitis mouse model and dosing Condition
Principle of experiment
MOG for C57BL/6 mice 35-55 An Experimental Autoimmune Encephalomyelitis (EAE) model is induced.
Experimental method
Female C57BL/6 mice, 6-8 weeks old, 18-20g weight, adapted for 3-5 days after feeding, MOG subcutaneous injection 35-55 300 μg and 600ng pertussis toxin were intraperitoneally injected to establish an experimental autoimmune encephalomyelitis animal model (EAE). Normal control group was set, n=10. Animal opening 12 days after modelingInitial disease, limb paralysis with different degrees appears. Mice presenting with quadriplegia were selected as experimental autoimmune encephalomyelitis models.
Female C57BL/6 mice were randomized on day 13 of modeling into 2 groups, EAE control group (n=10) and 100mg/kg puerarin dosing group (n=10). After grouping, the administration was performed by lavage once daily. The normal control group and the EAE model group were given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na). Puerarin was continuously dosed to day 35 of modeling. Body weight and disease scores were measured daily and animal mortality was recorded. The suspension rating of the animals was determined on days 7, 14, 21, 28 and 35 post immunization, and the suspension time of the animals on wire was determined on day 35.
Experimental results
Animals begin to develop disease on day 12 post immunization, and weight loss and reduced neurological scores occur.
1.2 Puerarin effect on body weight of EAE mice
Experimental method
Body weight is an important indicator of the energy utilization balance and growth of animals. The animal's activity status, hair, etc. were observed and recorded daily in this experiment, and the animal's weight was monitored daily.
Experimental results
In this experiment, mice in the EAE model group had significantly lower body weight than the normal group after onset. And after the administration, compared with a model group, the body weight of the puerarin treatment group mice in the later administration period is obviously increased. The results are shown in FIG. 1.
1.3 Effect of puerarin on EAE mouse disease score
Experimental method
Experimental mice were scored daily after modeling for disease, with the following scoring criteria: 0 point: normal mice; 0.5 point: tail weakness; 1, the method comprises the following steps: complete paralysis of the tail; 1.5 minutes: weakness of a hind limb; 2, the method comprises the following steps: weakness of both hind limbs; 2.5 minutes: paralysis of one hind limb and weakness of the other hind limb; 3, the method comprises the following steps: paralysis of both hind limbs; 3.5 minutes: part of the forelimb is weak; 4, the following steps: partial paralysis of the forelimbs; 4.5 minutes: complete paralysis of the forelimbs; 5, the method comprises the following steps: death.
Experimental results
In this experiment, the disease score of mice in the EAE model group after onset was significantly higher than that of mice in the normal control group, and the disease score of mice in the puerarin treatment group after administration was significantly lower than that of mice in the EAE model group. The results are shown in FIG. 2.
1.4 Effect of puerarin on EAE mouse suspension time
Experimental method
On day 35 after modeling, the drop time of mice from 180 ° wire mesh was determined, time > 120s calculated as 120s, and each mouse was repeated three times.
Experimental results
In this experiment, the suspension time on wire netting was significantly reduced in mice of EAE model group compared to normal control group, while puerarin can prolong the suspension time in model mice. The results are shown in FIG. 3 and Table 1.
TABLE 1 influence of puerarin on MOG-induced EAE mice suspension time
Figure BDA0003438676800000071
Mean±SEM(n=10)
# # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
1.5 Effect of puerarin on EAE mouse suspension fractionation
Experimental method
On days 7, 14, 21, 28 and 35 after modeling, the front paws of the mice were hung on a balance rope 30cm from the ground, and the limb hanging state of the mice on the balance rope was observed and scored, and the grading standard was as follows: 5, the method comprises the following steps: the rope is grabbed and can be pulled by the hind limb, and the tail is tightly wound around the rope; 4, the following steps: the rope is grabbed and can be pulled by the hind limb, and the tail is lifted but can not be wound; 3, the method comprises the following steps: the rope is grabbed and can be pulled by the hind limb, and the tail sags; 2, the method comprises the following steps: lifting the hind limb, and grasping the rope but not pulling; 1, the method comprises the following steps: lifting the hind limb, but not grasping the rope; 0 point: the hind limb cannot be lifted.
Experimental results
In this experiment, the suspension score was significantly reduced after the onset of mice in the EAE model group compared to the normal control group, whereas the suspension score was significantly increased and time-dependent in the drug-treated group compared to the EAE model group after administration. The results are shown in FIG. 4 and Table 2.
TABLE 2 influence of puerarin on MOG-induced EAE mice suspension fractionation
Figure BDA0003438676800000081
Mean±SEM(n=10)
# # P < 0.001vs. normal control group, # P < 0.001vs eae model group.
Example 2: effects of puerarin on infiltration and demyelination of myelitis cells in EAE model mice
2.1 Establishment of EAE mouse model and drug administration condition
The experimental principle, experimental method and experimental result are the same as those of example 1.1.
2.2 Effect of puerarin on the infiltration of inflammatory cells in the spinal cord of EAE mice
Experimental method
On day 35 after modeling, 3 mice per group were anesthetized with 4% tribromoethanol. And (3) firstly, irrigating with normal saline, and then irrigating with 4% paraformaldehyde until the liver turns white. Breaking the head, taking the spinal cord waist expansion part, and placing the spinal cord waist expansion part into 4% paraformaldehyde for fixation. Paraffin sections are prepared from the expanded spinal cord and stained with hematoxylin-eosin (H & E), and the inflammatory cell infiltration of spinal cord is observed.
Experimental results
In the experiment, compared with a normal control group, the EAE model group mice have obvious infiltration of spinal cord inflammatory cells, and 100mg/kg puerarin can obviously reduce the infiltration area of inflammatory cells. The results are shown in FIG. 5.
2.3 Effect of puerarin on the demyelination in the spinal cord of EAE mice
Experimental method
On day 35 after modeling, 3 mice per group were anesthetized with 4% tribromoethanol. And (3) firstly, irrigating with normal saline, and then irrigating with 4% paraformaldehyde until the liver turns white. Breaking the head, taking the spinal cord waist expansion part, and placing the spinal cord waist expansion part into 4% paraformaldehyde for fixation. Paraffin sections were prepared for the enlarged portion of the spinal cord, stained with solid blue (LFB), and observed for demyelination in the spinal cord.
Experimental results
In this experiment, after LFB staining, the spinal cord of mice in EAE model group exhibited demyelination lesions with larger area compared to normal control group. And puerarin can reduce the whitening area of the spinal cord white matter area, so that the demyelination situation is effectively improved. The results are shown in FIG. 6 and Table 3.
TABLE 3 effect of puerarin on MOG-induced EAE mice spinal cord demyelination
Figure BDA0003438676800000091
Mean±SEM(n=3)
# P <0.01vs. normal control group, # P <0.01vs. eae model group.

Claims (8)

1. The application of puerarin shown in the formula (I) in preparing medicines for preventing, relieving and/or treating autoimmune demyelinating diseases;
Figure FDA0003438676790000011
2. the use according to claim 1, characterized in that the autoimmune demyelinating diseases include demyelinating autoimmune diseases of the Central Nervous System (CNS) such as multiple sclerosis, neuromyelitis optica spectrum diseases, acute disseminated encephalomyelitis, white matter encephalitis and transverse myelitis; demyelinating autoimmune diseases affecting the peripheral nervous system, chronic inflammatory demyelinating polyneuropathy, anti-MAG peripheral neuropathy, motor and sensory neuropathy, hereditary sensory motor neuropathy, fibula atrophy, progressive neurofibula atrophy.
3. The use according to claim 2, wherein the demyelinating autoimmune disease affecting the peripheral nervous system comprises acute inflammatory demyelinating polyneuropathy.
4. The use according to claim 2, characterized in that the multiple sclerosis comprises relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, secondary progressive multiple sclerosis and progressive relapsing multiple sclerosis.
5. The application of a pharmaceutical composition in the prevention, alleviation and/or treatment of autoimmune demyelinating diseases is characterized in that the pharmaceutical composition contains puerarin shown in a formula (I) in an effective dose, and optionally pharmaceutically acceptable carriers and/or auxiliary materials;
Figure FDA0003438676790000012
6. the use according to claim 5, characterized in that the pharmaceutical composition contains, in addition to puerarin as pharmaceutical active ingredient, other active ingredients.
7. The use according to any one of claims 5-6, characterized in that the pharmaceutical composition comprises the following dosage forms: solutions, suspensions, lyophilized powders, emulsions, pills, capsules, powders, controlled release, sustained release formulations, and microsomal delivery systems.
8. The use according to claim 5, characterized in that said pharmaceutically acceptable excipients comprise starch, dextrin, sodium polymethylcellulose, magnesium stearate, talc.
CN202111625337.8A 2021-12-28 2021-12-28 Application of puerarin in preparing medicine for preventing or treating autoimmune demyelinating diseases Pending CN116350620A (en)

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