LU101639B1 - Application of Ilexgenin O in preparation of medicament for preventing and treating senile dementia - Google Patents
Application of Ilexgenin O in preparation of medicament for preventing and treating senile dementia Download PDFInfo
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- LU101639B1 LU101639B1 LU101639A LU101639A LU101639B1 LU 101639 B1 LU101639 B1 LU 101639B1 LU 101639 A LU101639 A LU 101639A LU 101639 A LU101639 A LU 101639A LU 101639 B1 LU101639 B1 LU 101639B1
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- ilexgenin
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- senile dementia
- preventing
- medicament
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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Abstract
The present invention discloses an application of ilexgenin O in a preparation of a medicament for preventing and treating senile dementia. Alzheimer's disease is a disease mainly characterized by primary and progressive degenerative diseases of the central nervous system with clinical manifestation of irreversible deterioration of cognitive and memory functions, mainly due to the neuron damage caused by excessive Ap deposits in the brain. The present invention finds that ilexgenin O can prevent nerve cell damage caused by Ap, and thus has the prospect of being developed into an anti-senile dementia drug.
Description
PREVENTING AND TREATING SENILE DEMENTIA Technical Field The present disclosure belongs to the field of medicine and relates to novel applications of known compounds. More specifically, the present invention relates to an application of ilexgenin O in the preparation of a medicament for preventing and treating senile dementia. Background Alzheimer's disease (AD), also known as senile dementia, is a disease characterized by progressive mental deterioration and neuronal loss. Currently, about 5-10% of the elderly people over 65 years old in the world, approximately 35 million, suffer from this disease. Patients with this disease have a life span of only three to nine years after a confirmed diagnosis. This disease has become the third leading killer of the elderly after cardiovascular and cerebrovascular disease and cancer. AD is a disease mainly characterized by primary and progressive degenerative diseases in the central nervous system with a clinical manifestation of irreversible deterioration of cognitive and memory functions. Neuron damage caused by excessive amyloid beta (AB) deposits in the brain is the main pathological factor of this disease. In recent years, there have been much research on the etiology and pathology of AD, and the relatively generally accepted pathological characteristics include a large number of death and loss of cholinergic neurons in the central nervous system caused by the neurotoxicity generated by senile plaques formed by excessive A deposits in the brain. Therefore, inhibiting the deposition of AB or reducing the damage of AB to neuron cells has become a research hotspot and one of the main directions of drug development. Ilexgenin O is a natural glycoside product isolated from plants of the genus Ilex in thefamily Aquifoliaceae. Currently, no reports disclose that ilexgenin O has an effect on preventing senile dementia.
Summary The objective of the present invention is to provide an application of ilexgenin O in the preparation of a medicament for preventing and treating senile dementia.
The above objective of the present invention is realized by the following technical solutions.
An application of ilexgenin O in a preparation of a medicament for preventing and treating dementia is provided.
An application of a pharmaceutically acceptable salt of ilexgenin O in a preparation of a medicament for the prevention and treatment of senile dementia is provided.
A medicinal preparation for preventing and treating senile dementia includes ilexgenin O or a pharmaceutically acceptable salt of ilexgenin O as an active pharmaceutical ingredient to prepare a pharmaceutically acceptable preparation form.
Preferably, the preparation form is a tablet, capsule, injection or oral solution.
Advantages: Alzheimer's disease is a disease mainly characterized by primary and progressive degenerative diseases of the central nervous system with clinical manifestation of irreversible deterioration of cognitive and memory functions, mainly due to the neuron damage caused by excessive AB deposits in the brain. The present invention finds that ilexgenin O can prevent nerve cell damage caused by AP, and thus has the prospect of being developed into an anti-senile dementia drug. Detailed Description of the Embodiments I. Experimental materials AB25-35 was purchased from Beijing Boaosen Biotechnology Co., Ltd. Dimethyl sulfoxide (DMSO) was purchased from Shanghai Maclean Biochemical Technology Co.,
Ltd. Methyl thiazolyl tetrazolium (MTT) was purchased from Dalian Meilun Biotechnology Co., Ltd. Ilexgenin O was purchased from Chengdu Purfield Biotechnology Co., Ltd. Fetal bovine serum was purchased from Zhejiang Tianhang Biotechnology Co., Ltd. RPMI-1640 medium was purchased from the company Hyclone.
Preparation of condensed AB25-3s: 1 mg of AB25-35 was first dissolved in an appropriate amount of sterile double distilled water (dd H20), then was added with medical sterile saline to make the final concentration of AB25-35 to 1 mM, and was incubated in a water bath at 37°C for 7 days.
II. Experimental method
1.Cell culture The rat glioma cell C6 cell line frozen in liquid nitrogen was taken out and quickly placed in the water bath at 37°C and shaken until the cells melt, and was then transferred into a centrifuge tube added with a medium. The centrifuge tube was centrifuged at 1000 rpm for 5 min, the supernatant was discarded, a small amount of the medium was added and gently blown and sucked to make the cells evenly. The medium is RPMI-1640 medium containing 10% fetal bovine serum and 1% two antibiotics. The cell suspension was transferred to a petri dish and cultured at 37°C, 5% CO», and saturated humidity.
2. Preparation of cell model C6 cells during the logarithmic growth phase were prepared into a cell suspension with a concentration of 2.0 x 10° cells/mL, seeded in a 96-well plate with 100 pL per well, and cultured for 24 h. The cells were processed in the following groups, with 5 replicates in each group.
Control group: change to fresh medium and continue to culture for 3 h.
AB25-35 group (model group): change to fresh medium and continue to culture for 3 h.
Donepezil hydrochloride group (positive drug group): change to fresh medium containing 20 uM donepezil hydrochloride and continue to culture for 3 h.
Ilexgenin O group: change to fresh mediums containing 2.5 and 20 uM ilexgenin O respectively and continue to culture for 3 h.
After 3 hours of incubation according to the above groups, the AB25-3s group, donepezil hydrochloride group, and ilexgenin O group were added with the condensed AB25.35 with a final concentration of 10 pM, and the control group was added with an equal volume of menstruum. After 18 h of incubation, each group was added with 20 uL of MTT solution (the concentration is 5 mg/mL), and continued to incubate at 37°C for 4 h.
After 4 hours of incubation, the supernatant was carefully discarded from the wells, 150 uL of DMSO was added to each well, and was shaken for 10 min to fully dissolve the crystals. The light absorption value (OD value) of each well on an enzyme-linked immunosorbent detector was determined at the wavelength of 490 nm. The cell survival rate was calculated according to the average of the OD values of 5 duplicate wells. The control group is recorded as 100%.
4. Data processing and analysis SPSS19.0 software was used. The comparison between multiple groups was tested by single-factor variance analysis. The comparison between the two groups was tested by q test. The difference with P <0.05was considered to be statistically significant.
III. Experimental results The cell survival rate of each group is shown in Table 1 (Note: compared with the control group #p <0.05, ## p <0.01, ### p <0.001; and compared with the AB25-35 group * p <0.05, ** p < 0.01, *** p <0.001).
Table 1. Effect of ilexgenin O on AB25-35s-induced cell damage Group Cell survival rate (%) Control group 100+3.641 AB25-35 group 79.97+1.902## Donepezil hydrochloride group (20 pM) 84.83+2.898** Ilexgenin O group (2.5 uM) 84.885.595 Ilexgenin O group (20 pM) 90.00+3.329%**
Compared with the control group, the cell survival rate of the AP25-3s group was significantly reduced, indicating that the cell modeling was successful.
Compared with the AB25.35 group, the cell survival rates of the donepezil hydrochloride group and ilexgenin O group were significantly increased.
Donepezil hydrochloride is a drug approved by the US Food and Drug Administration (FDA) for the treatment of Alzheimer's disease. 20 uM of donepezil hydrochloride can increase the cell survival rate by about 5%, while 5 uM of ilexgenin O can increase the cell survival rate by 5%. With the increase of the dose, the protective effect is enhanced.20 uM of ilexgenin O can increase the survival rate by about 10%, and the data has a statistical difference.
In order to exclude false positives caused by cell proliferation promoted by ilexgenin O, a test of the effect of ilexgenin O on cell
| viability without AB intervention was performed.
The results are shown in Table 2. Ilexgenin O had no effect on cell viability at concentrations of 2.5 and 20 uM (P > 0.05). This result indicates that ilexgenin O did not cause cell proliferation.
Table 2. Effect of ilexgenin O on C6 cell proliferation Control group 100+1.75 Ilexgenin O group (2.5 uM) 99.49+6.67 Ilexgenin O group (20 uM) 98.13+8.39
Therefore, based on the results in Tables 1 and 2, the results show that ilexgenin O can | protect nerve cell damage caused by AB, and has the prospect of developing into an anti- senile dementia drug.
Claims (4)
1. An application of ilexgenin O in a preparation of a medicament for preventing and treating senile dementia.
2. An application of a pharmaceutically acceptable salt of ilexgenin O in a preparation of a medicament for the prevention and treatment of senile dementia.
3. A medicinal preparation for preventing and treating senile dementia, comprising ilexgenin O or a pharmaceutically acceptable salt of ilexgenin O as an active pharmaceutical ingredient to prepare a pharmaceutically acceptable preparation form.
4. The medicinal preparation of claim 3, wherein a form of the medicinal preparation is a tablet, capsule, injection or oral solution.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910024764.7A CN109528739B (en) | 2019-01-10 | 2019-01-10 | Application of ilexoside O in preparing medicine for preventing and treating senile dementia |
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| Publication Number | Publication Date |
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| LU101639B1 true LU101639B1 (en) | 2020-06-15 |
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| LU101639A LU101639B1 (en) | 2019-01-10 | 2019-11-19 | Application of Ilexgenin O in preparation of medicament for preventing and treating senile dementia |
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| CN (1) | CN109528739B (en) |
| LU (1) | LU101639B1 (en) |
| WO (1) | WO2020143332A1 (en) |
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| CN109528739B (en) * | 2019-01-10 | 2020-08-25 | 河南中医药大学 | Application of ilexoside O in preparing medicine for preventing and treating senile dementia |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20120015874A (en) * | 2010-08-13 | 2012-02-22 | 주식회사한국신약 | Pharmaceutical compositions for prevention or treatment of cerebrovascular disease, or for improving impairments, containing the extracts of ilex latifolia as an active ingredient |
| CN109528739B (en) * | 2019-01-10 | 2020-08-25 | 河南中医药大学 | Application of ilexoside O in preparing medicine for preventing and treating senile dementia |
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- 2019-01-10 CN CN201910024764.7A patent/CN109528739B/en active Active
- 2019-11-19 LU LU101639A patent/LU101639B1/en active IP Right Grant
- 2019-11-19 WO PCT/CN2019/119367 patent/WO2020143332A1/en active Application Filing
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| Publication number | Publication date |
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| CN109528739B (en) | 2020-08-25 |
| WO2020143332A1 (en) | 2020-07-16 |
| CN109528739A (en) | 2019-03-29 |
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