Application of asarol or substance containing asarol to preparation of medicine for promoting neural stem cell proliferation

A technology of neural stem cells and asarum is applied in the field of drug research and development to achieve the effect of combating cognitive decline and promoting nerve regeneration

Pending Publication Date: 2016-12-07
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Application of asarol or substance containing asarol to preparation of medicine for promoting neural stem cell proliferation
  • Application of asarol or substance containing asarol to preparation of medicine for promoting neural stem cell proliferation
  • Application of asarol or substance containing asarol to preparation of medicine for promoting neural stem cell proliferation

Examples

Experimental program
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Effect test

Embodiment 1

[0043] Example 1 Preparation of Acorus calamus extract and separation of components

[0044] In this example, Acorus calamus extract (AT) was prepared, and quality control was performed by high performance liquid chromatography.

[0045] 19.5 kg of dried roots of Acorus calamus were reflux extracted with 70 L of 60% ethanol for 3 times, 2 hours each time. The obtained extracts were combined and concentrated by evaporation to obtain 2.2 kg of total extract (AT) of Acorus calamus, and the preparation yield was 11.3% (w / w). Dissolve AT in 10L of distilled water, separate the components with ethyl acetate (10L, repeated three times) and n-butanol (10L, repeat three times), and then remove the organic solvent by vacuum evaporation. The obtained components are (1) Fraction in ethyl acetate (ATE), 346.8 g, yield 1.8%, (2) fraction soluble in n-butanol (ATB), 127.4 g, yield 0.7%, and (3) remaining soluble in water The component (ATW), 1.25kg, yield 6.4%. The composition and content...

Embodiment 2

[0046] Example 2 Experimental method

[0047] (1) Mice administration and BrdU injection

[0048] α-Asarone, β-Asarone and AT were dissolved in water containing 0.8% Tween-80. In the administration experiment of 8-week-old young mice, each mouse was intragastrically administered 100μl, and the administration concentrations were α-asarone 10mg / kg mouse body weight, β-asarone 30mg / kg mouse Body weight and AT 20g / kg mouse body weight, another reference group was given 100 μl of water containing 0.8% Tween-80, once a day, for 28 days, and in the 5-day short-term administration experiment, it was given for 5 days . In the experiment of detecting the proliferation of neural stem cells in vivo, after the last administration, BrdU of 150 mg / kg mouse body weight was injected intraperitoneally in 3 times, with an interval of 3 hours between each time, and 2 hours after the last BrdU injection, the mice were anesthetized and PFA After perfusion, the whole brain was taken for the next ...

Embodiment 3

[0069] Example 3 Shichangpu promotes the proliferation of neural stem cells in adult mice

[0070] We gave 8-week-old C57BL / 6 mice oral AT at the dose of 200mg raw medicinal materials / 20g body weight; mice in the control group were orally given a corresponding volume of solvent (vehicle, 0.8% Tween-80 dissolved in water), and administered intragastrically, every day 1 time, a total of 28 days. On the last day, bromodeoxyuridine (BrdU) was injected 3 times to label proliferating cells. The results of immunohistochemical analysis showed that most of the BrdU-positive cells were located in the subgranular zone (SGZ) where neural stem cells were concentrated. Oral administration of AT increased the number of BrdU-positive cells by 31% compared to control mice (eg figure 1 B-D shown). The staining of another proliferation marker molecule Ki67 also obtained similar results (such as figure 1 K,L, figure 2 shown in B). However, AT did not significantly change the volume of the ...

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Abstract

The invention belongs to the field of drug research and development, and in particular relates to the use of asarone or a substance containing asarone in the preparation of drugs for promoting the proliferation of neural stem cells. The present invention finds for the first time that oral administration of Shichangpu can promote hippocampal nerve regeneration in wild-type mice, transgenic AD model mice and aged mice. In vitro and in vivo experiments, Shichangpu and its active ingredient asarone promote the proliferation of neural stem cells. Calamus calamus and asarone activate ERK cascade without affecting Akt cascade. The research of the present invention shows that oral administration of calamus and asarone can not only prevent, but also act as a therapeutic means to promote nerve regeneration, to resist the decline of cognitive function related to aging and neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the field of drug research and development, and in particular relates to the use of asarone or a substance containing asarone in the preparation of drugs for promoting the proliferation of neural stem cells. Background technique [0002] In the mammalian brain, the proliferation and self-renewal of neural progenitor cells (NPCs) continues throughout life, and is an important part of neurogenesis. In aging, chronic stress, and neurological diseases such as Alzheimer's disease (AD), the proliferation and self-renewal abilities of neural stem cells are reduced, resulting in impaired cognitive function. Promoting nerve regeneration is considered a potential therapeutic approach to combat aging and age-related neurodegenerative diseases. Therefore, a possible solution is to transplant embryonic neural stem cells or induced neural stem cells in vitro for cell replacement therapy. However, there are still some controversies about th...

Claims

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Application Information

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IPC IPC(8): A61K31/09A61K36/888A61P25/28
Inventor 裴钢赵简毛坚鑫黄世超
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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