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Application of asparagine synthetase activator

A technology of asparagine and synthetase, which is applied in the field of medicine, can solve the problems of patient burden, operation cost, large number of people, and unsatisfactory effect, so as to improve cell activity, broaden prevention and treatment ideas, and avoid lens turbidity. Effect

Active Publication Date: 2021-06-22
上海优祺生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there is no specific drug for cataract, and surgical treatment is still the main method. The most common drug for treating cataract is antioxidant (glutathione, vitamins, etc.) , Aldose reductase inhibitors (Sobinil, Epalrestat, Torrestat, Ponarestat, etc.), Glycosylation inhibitors (Aminoguanidine, Pyruvate, Taurine, etc.), Chinese medicine preparations (cornus officinale polysaccharide, dodder, lanosterol, etc.), but there are still some patients who cannot achieve the desired effect of the above-mentioned treatment measures in clinical practice, there are postoperative complications, surgical costs and too many people who need to undergo surgery. A burden on society and many patients

Method used

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  • Application of asparagine synthetase activator
  • Application of asparagine synthetase activator
  • Application of asparagine synthetase activator

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] This embodiment is used to verify that the expression level of ASNS in the lens of naphthalene cataract rats increases, specifically including:

[0032] After the cataract rat lens was treated with naphthalene for 2 weeks, the lens appeared cloudy in different degrees. The present invention classifies according to any naphthalene cataract grading system ( figure 1 A-D) of different degrees of cataract classification. The turbidity of lens treated with naphthalene reached 2 points in 2 weeks (n=6, as figure 1 Shown in F), and reached 4 points in 4 weeks (n=6, such as figure 1 Shown in G), the lens turbidity of the non-treatment group (normal) and the mineral oil treatment group (control) was lower than 2 points. In order to explore the mechanism of naphthalene-induced lens turbidity, the lenses of the naphthalene cataract group and the control group were collected after 1 week of treatment, and RNA was prepared for gene array analysis. Control group increased (n=6, p...

Embodiment 2

[0034] This example is used to verify the oxidation of 1,2-DHN and the increased expression of ASNS under the action of naphthalene metabolite 1,2-DHN, specifically including:

[0035] Using the NADP / NADPH kit, it was found that when different substrates were co-incubated with lens homogenates, the NADPH production of the 1,2-DHN mixture increased over time, but not the N ADPH mixture, which indicated that The lens can promote the oxidation of 1,2-DHN, and it is an autoxidative process (n=3, such as figure 2 shown in A), remove the lens homogenate in the 1,2-DHN oxidation reaction system (n=3, such as figure 2 As shown in D), it was found that the amount of NADPH generated in the lens homogenate system was higher than that in the system without homogenate. NADPH time effect (n=3, such as figure 2 Shown in B and C), it was confirmed that the lens was incubated with 50 μM 1.2-DHN or 50 μM NQ solution for 6 hours, and the lens was collected for western blot detection. Compar...

Embodiment 3

[0037] This embodiment is used to verify that ASNS reduces the decline caused by 1,2-DHN on cell viability and slows down its oxidation rate, specifically including:

[0038] like image 3 As shown, ASNS was overexpressed and knocked down in the SRA01 / 04 cell line with lentivirus respectively, wherein, such as image 3 As shown in A, the relative expression of ASNS at the mRNA level in the SRA01 / 04 cell line overexpressing ASNS and knocking down ASNS was detected by real-time fluorescent quantitative PCR experiment; image 3 B and image 3 As shown in C, the relative expression of ASNS at the protein level in the SRA01 / 04 cell lines overexpressing ASNS and knocking down ASNS was detected by Western blot. In addition, the cell viability of ASNS overexpression (OE), ASNS knockdown (shASNS) and control group (CTL) was detected by MTT method. Compared with the control group, the cell viability of ASNS knockdown group was significantly decreased (n=3, p Figure 4 As shown in A), t...

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Abstract

The invention is applicable to the technical field of medicines, provides an application of an asparagine synthetase activator, and particularly relates to an application of the asparagine synthetase activator in preparation of medicines for preventing and treating cataract and / or related diseases thereof; the cell functions maintained by ASNS are determined; the application comprises improvement of cell viability, slowing down of capability of oxidizing 1,2-DHN into NQ and the like, and the asparagine synthetase activator has an obvious treatment effect on cataract. By using the ASNS activator, the effect of relieving damage of external stimulation to lenticular epithelial cells is achieved, the cataract occurrence process can be effectively slowed down, lenticular opacification is avoided, the asparagine synthetase activator is expected to become a new target for treating age-related cataract, and a reference basis is provided for cataract drug development.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to the application of an asparagine synthetase activator. Background technique [0002] Cataract, clouding of the lens of the eye, is the leading cause of blindness worldwide. Cataract involves a multifactorial disease process, which may be caused by various toxic factors, environmental stress, aging, diabetes, genetic factors, etc., which can lead to the occurrence of age-related cataract, diabetic cataract, congenital cataract and many other types. Diabetic cataract is one of the most common complications of diabetes and one of the main causes of visual impairment in diabetic patients. Diabetic cataract patients account for a large part of all cataract patients. Age-related cataracts are common in people after the age of 40, and with age, the lens becomes cloudier, hardens and eventually blocks light from reaching the retina. [0003] The etiology of cataract remains elusive an...

Claims

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Application Information

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IPC IPC(8): A61K31/551A61K31/352A61K31/04A61P27/12
CPCA61K31/551A61K31/352A61K31/04A61P27/12
Inventor 徐国彤徐晶莹杨依婷
Owner 上海优祺生物医药科技有限公司