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New application of guanosine

A technology for guanine nucleoside and uses, applied in the field of NF-κB, STAT3 inhibitors or drugs for treating asthma, and preparation of MAPK

Pending Publication Date: 2020-10-30
WEST CHINA HOSPITAL SICHUAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The effect of guanosine on asthma and its molecular mechanism have not been reported yet

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Guanosine reduces airway inflammation in asthmatic mice induced by ovalbumin (OVA) The experimental procedure of this example is as follows:

[0043] (1) Establishment of asthma animal model

[0044] Newly purchased balb / c female mice at the age of 4-6 weeks were bred in an SPF-grade environment for one week before the experiment was carried out.

[0045] 1) On the 1st and 14th day, the negative control group was intraperitoneally injected with 100 μL of 0.9% NaCl; except the negative control group, each mouse in the other groups was intraperitoneally injected with 100 μL of a solution containing 40 μg of ovalbumin (OVA) and 4 mg of aluminum adjuvant.

[0046] 2) On the 24th to 26th day, the mice inhaled 1% OVA solution (dissolved in PBS) by ultrasonic atomization for 30 minutes, and the negative control group inhaled the nebulized PBS buffer solution for 30 minutes. One hour before nebulization, the dexamethasone group was intraperitoneally injected with 1 ...

Embodiment 2

[0063] Example 2: Guanine nucleoside alleviates airway fibrosis in asthmatic mice induced by ovalbumin (OVA)

[0064] In this example, an animal model of asthma was established in the same manner as in Example 1.

[0065] Then perform Masson staining:

[0066] On day 27, after the detection of airway hyperresponsiveness, the left lung lobe was placed in an embedding frame, fixed with 4% paraformaldehyde, routinely dehydrated and embedded, sectioned at a thickness of 4 μm, and then stained according to the following steps:

[0067] 1) Dewaxing: xylene (I) 10min, xylene (II) 10min

[0068] 2) Rehydration: Soak in 100%, 95%, 80%, and 60% in turn for 5 minutes; wash with double distilled water 3 times, 3 minutes each time;

[0069] 3) Weigert hematoxylin staining for 8 minutes;

[0070] 4) Differentiate with acidic ethanol for 5 seconds, wash with distilled water for 1 minute;

[0071] 5) Masson blue solution was turned blue for 3 minutes, and washed with distilled water for 1...

Embodiment 3

[0079] Example 3: Guanosine significantly reduces airway hyperresponsiveness in asthmatic mice

[0080] Airway hyperresponsiveness is a major pathological feature of asthma. In this embodiment, the whole plethysmography system is used to measure the enhanced expiratory pause value (Penh) of mice after being challenged with different concentrations of acetylcholine chloride. The specific process is as follows:

[0081] In this example, an animal model of asthma was established in the same manner as in Example 1. On the 27th day, the mice were placed in the body scanning box of the whole plethysmography system to cool down for 10 minutes, and then given 0, 12.5, 25, 50, 100 mg / mL acetylcholine chloride solution for 2 min, and after each atomization, Record the Penh value within 6 minutes.

[0082] The result is as Figure 4 As shown, the Penh value of the mice in the asthma model group was significantly higher than that of the negative control group; compared with the model gr...

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to new application of guanosine, in particular to new application of guanosine in preparation of medicines for treating asthma or inhibitors of MAPK, NF-kappa B and STAT3. The invention aims to solve the problem that safer and more effective asthma treatment medicines need to be developed urgently in the prior art.It is found that in an in-vitro THP-1-derived macrophage inflammation model, guanosine inhibits generation of a proinflammatory factor IL-6 by inhibiting activation of MAPK and NF-kappa B; in an asthma mouse model, guanosine reduces OVA-IgE of mouse plasma, reduces generation of IL-4, IL-6 and IL-13, relieves airway high reactivity, and relieves lung tissue cell infiltration, airway inflammationand collagen deposition. In addition, the expression levels of p-p38 MAPK, p-p65 NF-kappa B, p-I kappa B alpha and p-STAT3 proteins in lung tissues of mice in a guanosine treatment group are obviouslylower than those in an asthma model group. Therefore, the invention provides application of guanosine in preparation of a p38 MAPK inhibitor, a p65 NF-kappa B inhibitor, an STAT3 inhibitor or an asthma treatment drug.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to the new application of guanosine in preparing MAPK, NF-κB, STAT3 inhibitors or treating asthma drugs. Background technique [0002] Asthma is one of the most common chronic non-communicable diseases, with a prevalence of 4.3% in adults. The prevalence of asthma is increasing year by year. It is estimated that from 1990 to 2015, the number of patients with asthma rose to 358.2 million, an increase of 12.6%. In 2015, 400,000 people died of asthma. Although inhaled corticosteroids (ICS) are the first-line treatment for most patients, adherence to ICS in children and adults is poor, and a small proportion of patients are resistant to ICS. Because patients believe that short-acting β2 agonists (SABA) are more familiar and acceptable than ICS, cheaper and safer. Therefore, only 5.6% of asthma patients in China received conventional ICS treatment. However, according to ...

Claims

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Application Information

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IPC IPC(8): A61K31/708A61P11/06A61P11/08A61P35/00A61P29/00A61P25/00A61P17/06A61P9/10A61P25/28A61P31/18A61P19/02A61P19/08A61P11/00A61P25/24A61P1/02A61P25/02A61P35/02A61P31/12A61P3/10A61P1/04A61P1/16
CPCA61K31/708A61P11/06A61P11/08A61P35/00A61P29/00A61P25/00A61P17/06A61P9/10A61P25/28A61P31/18A61P19/02A61P19/08A61P11/00A61P25/24A61P1/02A61P25/02A61P35/02A61P31/12A61P3/10A61P1/04A61P1/16
Inventor 李为民罗雨蕉陈海何杨吴琼夏贞强黄日东
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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