Application of 2-deoxy-D-glucose in preparation of medicine for resisting systemic lupus erythematosus
By using 2-deoxy-D-glucose to treat SLE model mice, the shortcomings of existing drugs in reducing antibody levels and inhibiting renal inflammation were solved, and safe and effective treatment effects of systemic lupus erythematosus were achieved.
Patent Information
- Application Number
- CN202411483474.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-23
- Publication Date
- 2024-12-20
AI Technical Summary
Existing treatments for systemic lupus erythematosus have side effects and limited efficacy, especially in reducing anti-double-stranded DNA antibodies, anti-nuclear antibodies, IgG, inhibiting renal inflammation, alleviating renal collagen deposition and reducing renal glycogen accumulation Lack of effective drugs.
Using 2-deoxy-D-glucose as the active ingredient, SLE model mice were treated by intraperitoneal injection, which significantly reduced the level of antibody in serum, inhibited renal inflammation, alleviated collagen deposition and glycogen accumulation, and decreased renal C3 complement.
2-Deoxy-D-glucose treatment process is simple, non-toxic and has few side effects, is safe and reliable, significantly reduces the pathological indicators of SLE model mice, and has potential application value for anti-systemic lupus erythematosus.
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Figure CN119157889A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the application of 2-deoxy-D-glucose, in particular to the application of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug. Background Art
[0002] Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune disease characterized by the presence of a large number of autoantibodies in the body, with high expression of anti-double-stranded DNA antibodies, antinuclear antibodies, and IgG in the serum. As the disease progresses, 60% of clinical patients will have kidney involvement, accompanied by complications such as lupus nephritis, which are specifically manifested in renal collagen deposition, renal glycogen accumulation, and increased renal C3 complement. At present, the first choice drug for the treatment of systemic lupus erythematosus is glucocorticoids. When hormone therapy is ineffective or cannot be continued due to side effects, immunosuppressants and plasma exchange can be used. However, immunosuppressants and plasma exchange also have corresponding side effects. Although there are reports that biological agents can treat systemic lupus erythematosus, they have failed to reach clinical endpoints, limiting their clinical application.
[0003] 2-Deoxy-D-glucose (2DG) is a glucose analog that has been widely studied as a glycolysis inhibitor. It has been shown to have multiple properties including anti-tumor and anti-viral properties, but there are no reports on its use in the preparation of anti-systemic lupus erythematosus drugs. Summary of the invention
[0004] The present invention finds that 2-deoxy-D-glucose has an effect of resisting systemic lupus erythematosus, and further invents the use of 2-deoxy-D-glucose in preparing a drug for resisting systemic lupus erythematosus.
[0005] The technical solution of the present invention is: application of 2-deoxy-D-glucose in the preparation of anti-systemic lupus erythematosus drugs.
[0006] Specifically, it is used in the preparation of drugs for reducing anti-double-stranded DNA antibodies, anti-nuclear antibodies, and IgG in serum.
[0007] Specifically, it is used in the preparation of drugs for inhibiting kidney inflammation.
[0008] Specifically, it is used in the preparation of drugs for alleviating renal collagen deposition.
[0009] Specifically, the invention is used in the preparation of drugs for reducing renal glycogen accumulation.
[0010] Specifically, it is used in the preparation of drugs for reducing kidney C3 complement.
[0011] The present invention finds that 2-deoxy-D-glucose acts on SLE model mice, can reduce anti-double-stranded DNA antibodies, anti-nuclear antibodies, IgG in the serum of SLE model mice, inhibit kidney inflammation of SLE model mice, relieve kidney collagen deposition of SLE model mice, reduce kidney glycogen accumulation of SLE model mice and reduce kidney C3 complement, and can be used to prepare anti-systemic lupus erythematosus drugs. The treatment process is simple, non-toxic and has no side effects, and is safe and reliable. BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Figure 1 This is a schematic diagram of the effect of 2-deoxy-D-glucose on anti-double-stranded DNA antibodies, anti-nuclear antibodies, and IgG in the serum of SLE model mice.
[0013] Figure 2 This is a schematic diagram of the effect of 2-deoxy-D-glucose on renal inflammation in SLE model mice.
[0014] Figure 3 This is a schematic diagram of the effect of 2-deoxy-D-glucose on renal collagen deposition in SLE model mice.
[0015] Figure 4 This is a schematic diagram of the effect of 2-deoxy-D-glucose on renal glycogen deposition in SLE model mice.
[0016] Figure 5 This is a schematic diagram of the effect of 2-deoxy-D-glucose on C3 complement in the kidneys of SLE model mice. DETAILED DESCRIPTION
[0017] experiment: Experimental Example 1: Schematic diagram of the effect of 2-deoxy-D-glucose on anti-double-stranded DNA antibodies, anti-nuclear antibodies, and IgG in the serum of SLE model mice.
[0018] 1.1 Experimental Materials C57BL / 6J mice, female, were provided by Liaoning Changsheng Biotechnology Co., Ltd.
[0019] Imiquimod was provided by Tianfang Pharmaceutical Co., Ltd., and 2-deoxy-D-glucose was provided by Solebao.
[0020] 1.2 Experimental methods 1.2.1 Experimental Grouping Blank control group: normal C57BL / 6J mice.
[0021] SLE model group: Imiquimod-induced SLE model group, intraperitoneal injection of PBS.
[0022] Experimental group: SLE model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0023] 1.2.2 Experimental methods Seven-week-old female C57BL / 6J mice were randomly divided into groups, and 5% imiquimod ointment was evenly applied to the ears of the mice every other day for 8 consecutive weeks to establish the model. After the SLE model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat SLE mice, 3 times a week. After 2 weeks of treatment, the mice were killed and serum was collected to measure serological indicators such as anti-double-stranded DNA antibodies, anti-nuclear antibodies, and IgG.
[0024] 1.2.3 Experimental Results After 2-deoxy-D-glucose treatment, the serum levels of anti-double-stranded DNA antibodies, anti-nuclear antibodies, and IgG in SLE model mice decreased significantly (see Figure 1 ).
[0025] Experimental Example 2: Schematic diagram of the effect of 2-deoxy-D-glucose on renal inflammation in SLE model mice.
[0026] 2.1 Experimental Materials C57BL / 6J mice, female, were provided by Liaoning Changsheng Biotechnology Co., Ltd.
[0027] Imiquimod was provided by Tianfang Pharmaceutical Co., Ltd., and 2-deoxy-D-glucose was provided by Solebao.
[0028] 2.2 Experimental methods 2.2.1 Experimental Grouping Blank control group: normal C57BL / 6J mice.
[0029] SLE model group: Imiquimod-induced SLE model group, intraperitoneal injection of PBS.
[0030] Experimental group: SLE model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0031] 2.2.2 Experimental methods Seven-week-old female C57BL / 6J mice were randomly divided into groups, and 5% imiquimod ointment was evenly applied to the ears of the mice every other day for 8 consecutive weeks to establish the model. After the SLE model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat SLE mice, 3 times a week, and the mice were killed after 2 weeks of treatment to collect kidneys for sectioning and HE staining.
[0032] 2.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, renal inflammation in SLE model mice was significantly alleviated (see Figure 2).
[0033] Experimental Example 3: Schematic diagram of the effect of 2-deoxy-D-glucose on renal collagen deposition in SLE model mice.
[0034] 3.1 Experimental Materials C57BL / 6J mice, female, were provided by Liaoning Changsheng Biotechnology Co., Ltd.
[0035] Imiquimod was provided by Tianfang Pharmaceutical Co., Ltd., and 2-deoxy-D-glucose was provided by Solebao.
[0036] 3.2 Experimental methods 3.2.1 Experimental Grouping Blank control group: normal C57BL / 6J mice.
[0037] SLE model group: Imiquimod-induced SLE model group, intraperitoneal injection of PBS.
[0038] Experimental group: SLE model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0039] 3.2.2 Experimental methods Seven-week-old female C57BL / 6J mice were randomly divided into groups, and 5% imiquimod ointment was evenly applied to the ears of the mice every other day for 8 consecutive weeks to establish the model. After the SLE model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat SLE mice, 3 times a week, and the mice were killed after 2 weeks of treatment to collect kidneys for sectioning and MASSON staining.
[0040] 3.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, the renal collagen deposition in SLE model mice was significantly alleviated (see Figure 3 ).
[0041] Experimental Example 4: Schematic diagram of the effect of 2-deoxy-D-glucose on renal glycogen deposition in SLE model mice.
[0042] 4.1 Experimental Materials C57BL / 6J mice, female, were provided by Liaoning Changsheng Biotechnology Co., Ltd.
[0043] Imiquimod was provided by Tianfang Pharmaceutical Co., Ltd., and 2-deoxy-D-glucose was provided by Solebao.
[0044] 4.2 Experimental methods 4.2.1 Experimental Grouping Blank control group: normal C57BL / 6J mice.
[0045] SLE model group: Imiquimod-induced SLE model group, intraperitoneal injection of PBS.
[0046] Experimental group: SLE model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0047] 4.2.2 Experimental methods Seven-week-old female C57BL / 6J mice were randomly divided into groups, and 5% imiquimod ointment was evenly applied to the ears of the mice every other day for 8 consecutive weeks to establish the model. After the SLE model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat SLE mice, 3 times a week, and the mice were killed after 2 weeks of treatment to collect kidneys for sectioning and PAS staining.
[0048] 4.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, renal glycogen deposition in SLE model mice was significantly alleviated (see Figure 4 ).
[0049] Experimental Example 5: Schematic diagram of the effect of 2-deoxy-D-glucose on renal C3 complement in SLE model mice.
[0050] The complement system can activate pro-inflammatory pathways, and dysregulation of the complement pathway directly or indirectly leads to various kidney diseases, or is closely related to a variety of kidney diseases.
[0051] 5.1 Experimental Materials C57BL / 6J mice, female, were provided by Liaoning Changsheng Biotechnology Co., Ltd.
[0052] Imiquimod was provided by Tianfang Pharmaceutical Co., Ltd., and 2-deoxy-D-glucose was provided by Solebao.
[0053] 5.2 Experimental methods 5.2.1 Experimental Grouping Blank control group: normal C57BL / 6J mice.
[0054] SLE model group: Imiquimod-induced SLE model group, intraperitoneal injection of PBS.
[0055] Experimental group: SLE model mice were intraperitoneally injected with 2-deoxy-D-glucose (500 mg / kg).
[0056] 5.2.2 Experimental methods Seven-week-old female C57BL / 6J mice were randomly divided into groups, and 5% imiquimod ointment was evenly applied to the ears of the mice every other day for 8 consecutive weeks to establish the model. After the SLE model was successfully established, 500 mg / kg of 2-deoxy-D-glucose dissolved in ddH2O and diluted in PBS was intraperitoneally injected to treat SLE mice 3 times a week. After 2 weeks of treatment, the mice were killed and the kidneys were collected for sectioning and immunofluorescence C3 complement staining.
[0057] 5.2.3 Experimental Results After treatment with 2-deoxy-D-glucose, the C3 complement content in the kidneys of SLE model mice decreased significantly (see Figure 5 ).
Claims
1. Use of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug.
2. The use of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug according to claim 1, characterized in that: The invention is used in the preparation of drugs for reducing anti-double-stranded DNA antibodies, anti-nuclear antibodies and IgG in serum.
3. The use of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug according to claim 1, characterized in that: The invention is used in the preparation of drugs for inhibiting kidney inflammation.
4. The use of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug according to claim 1, characterized in that: The invention is used in the preparation of medicine for alleviating renal collagen deposition.
5. The use of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug according to claim 1, characterized in that: The invention is used in the preparation of drugs for reducing renal glycogen accumulation.
6. The use of 2-deoxy-D-glucose in the preparation of an anti-systemic lupus erythematosus drug according to claim 1, characterized in that: The invention is used in the preparation of drugs for reducing renal C3 complement.