Application of isoquercitrin in preparation of medicine for treating systemic lupus erythematosus

Abstract

The invention provides an application of isoquercitrin in preparation of a medicine for treating systemic lupus erythematosus. The invention further provides a medicine for treating systemic lupus erythematosus. The medicine contains an effective therapeutic dose of isoquercitrin. The invention provides a novel method for treating systemic lupus erythematosus.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine and relates to a medicine for treating systemic lupus erythematosus, specifically to the use of isoquercetin in preparing a medicine for treating systemic lupus erythematosus. Background Art

[0002] Systemic lupus erythematosus is a chronic autoimmune disease that affects multiple organs and tissues, characterized by the production of multiple autoantibodies and the deposition of large amounts of immune complexes. The clinical manifestations of systemic lupus erythematosus are diverse, and common symptoms include rash, joint pain and swelling, fatigue, fever, nephritis, oral ulcers, photosensitivity, chest pain, etc., which may worsen or ease periodically and may relapse multiple times. The cause of the disease has not yet been fully understood and is related to multiple factors such as genetics, environment, and hormones. There is currently no cure for systemic lupus erythematosus, but drug treatment and management can be used to alleviate symptoms and control the progression of the disease.

[0003] Western medicine treatments for systemic lupus erythematosus mainly include nonsteroidal anti-inflammatory drugs, glucocorticoids, immunosuppressants, plasma exchange, intravenous immunoglobulin, and symptomatic treatment. This treatment model can control systemic lupus erythematosus in most cases, but a considerable number of patients may still respond poorly or relapse during the maintenance phase, and still face challenges such as unstable efficacy, drug side effects, and difficulties in individualized treatment. Therefore, more research and clinical practice are still needed to improve treatment strategies and develop more individualized and specific treatment methods.

[0004] Chinese medicine monomers have immunomodulatory effects, which can inhibit over-activated immune responses and reduce inflammatory responses, thereby treating immune diseases such as systemic lupus erythematosus. At the same time, Chinese medicine monomer components are a class of natural single-molecule multi-target drugs, which can act on multiple signaling proteins, exert functions on multiple cell functions of systemic lupus erythematosus, and achieve multi-target treatment. Chinese medicine monomer components are simple and can reduce adverse drug reactions. The treatment of systemic lupus erythematosus can reduce the side effects of infection and osteoporosis caused by hormones and immunosuppressants to a certain extent. Combining with existing treatments can help improve efficacy and reduce side effects.

[0005] Isoquercetin (ISQ) is a flavonol compound that exists in many plants in nature and has pharmacological effects such as hypoglycemic, antioxidant, anti-inflammatory, and anti-cancer. Previous studies in our laboratory have shown that isoquercetin, as one of the main active compounds in Abelmoschus alba, can reduce renal fibrosis and alleviate renal damage in diabetic nephropathy by inhibiting STAT3 phosphorylation. However, there are no reports on the role of isoquercetin in systemic lupus erythematosus.

[0006] Quercetin is also a flavonol compound, which is widely distributed in the plant kingdom and has multiple biological activities such as anti-inflammatory, antioxidant, and anti-tumor. Wang Rui and other studies have shown that quercetin treatment can effectively protect the renal function of systemic lupus erythematosus and improve its immune function. However, quercetin has poor water solubility and is almost insoluble in water, and its dissolution and absorption in vivo are average. In contrast, isoquercetin is soluble in water, has stronger water solubility, and has higher bioavailability. The glucose component in the isoquercetin molecule promotes its rapid uptake and conversion into quercetin in the small intestine. Compared with quercetin, isoquercetin has more advantages as a therapeutic monomer.

[0007] Although some progress has been made in the treatment of systemic lupus erythematosus, there are still some shortcomings and disadvantages:

[0008] (1) Unstable treatment efficacy: The treatment efficacy of systemic lupus erythematosus varies depending on individual patient differences, disease severity, disease activity, etc. Some patients are insensitive to or difficult to tolerate conventional treatments, and the treatment efficacy is unstable.

[0009] (2) Drug side effects: Commonly used drugs for the treatment of systemic lupus erythematosus include nonsteroidal anti-inflammatory drugs, glucocorticoids and immunosuppressants. However, long-term use of these drugs may lead to a series of side effects, including immunosuppression, osteoporosis, hypertension and infection.

[0010] (3) Disease recurrence and progression: Although treatment can temporarily relieve the symptoms of SLE, some patients may experience disease recurrence or progression after stopping medication. In addition, SLE may develop into more serious complications such as nephritis, cardiovascular disease, and central nervous system involvement.

[0011] (4) Difficulty in individualized treatment: There are great individual differences among patients with systemic lupus erythematosus, including disease severity, immunological characteristics, and drug resistance. Therefore, it is challenging to develop an individualized treatment plan suitable for each patient.

[0012] (5) Lack of specific treatment: Current treatments mainly alleviate the symptoms of systemic lupus erythematosus by suppressing inflammation and immune responses, but lack specific treatment for the cause. Therefore, for some patients, treatment may only control the disease symptomatically and cannot fundamentally change the condition. Summary of the invention

[0013] In view of the above technical problems in the prior art, the present invention provides the use of isoquercetin in the preparation of a drug for treating systemic lupus erythematosus. The use of isoquercetin in the preparation of a drug for treating systemic lupus erythematosus is intended to solve the technical problem that the prior art drugs are not effective in treating systemic lupus erythematosus.

[0014] The present invention provides use of isoquercetin in preparing a medicine for treating systemic lupus erythematosus.

[0015] Furthermore, the medicine also includes a pharmaceutically acceptable carrier and / or excipient.

[0016] Furthermore, the drug is a pharmaceutical preparation that is administered by injection, oral administration, nasal mucosa, lungs, rectum, oral mucosa or skin.

[0017] The invention also provides a medicine for treating systemic lupus erythematosus, which contains an effective therapeutic amount of isoquercetin.

[0018] Furthermore, the medicine also includes a pharmaceutically acceptable carrier and / or excipient.

[0019] Furthermore, the drug is a pharmaceutical preparation that is administered by injection, oral administration, nasal mucosa, lungs, rectum, oral mucosa or skin.

[0020] Compared with the prior art, the technical effect of the present invention is positive and obvious. As a traditional Chinese medicine extract, isoquercetin has the effect of treating systemic lupus erythematosus, reducing the level of autoantibodies, alleviating kidney pathological changes, and reducing proteinuria, providing a new method for treating systemic lupus erythematosus. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Schematic diagram of the molecular structure of isoquercetin.

[0022] Figure 2 Effects of isoquercetin on the general condition of lupus mice.

[0023] Figure 3 Isoquercetin reduces the urine protein / urine creatinine ratio in lupus mice.

[0024] Figure 4 Isoquercetin reduces serum creatinine and blood urea nitrogen in lupus mice.

[0025] Figure 5 Isoquercetin reduces anti-dsDNA levels in lupus mice.

[0026] Figure 6 Isoquercetin attenuates renal mesangial cell proliferation and mesangial extracellular matrix accumulation in lupus mice.

[0027] Figure 7 Isoquercetin reduces renal immune protein and complement deposition in lupus mice.

[0028] Figure 8 Isoquercetin attenuates macrophage infiltration in lupus mice. DETAILED DESCRIPTION

[0029] The present invention verifies its therapeutic effect on systemic lupus erythematosus through MRL / lpr lupus animal model experiments. The following experimental substances that are not specified are all commercially available substances.

[0030] Example 1 Preparation of Chinese medicine monomers and experimental grouping

[0031] Preparation of Chinese medicine monomer: Dissolve isoquercetin powder in 0.5% sodium carboxymethylcellulose (CMC-Na) solution and administer by gavage at a dose of 50 and 100 mg / kg once a day for 10 weeks. The control group and the model group were given the same CMC-Na solution. After 10 weeks of administration, the mice were anesthetized with 0.1% sodium pentobarbital to collect urine, blood, and spleen and kidney tissues.

[0032] Isoquercetin powder was purchased from Jiangsu Yongjian Pharmaceutical Technology Co., Ltd. Sodium carboxymethyl cellulose was purchased from Beijing Solaibao Technology Co., Ltd.

[0033] Experimental animals and groups: MRL / lpr mice were randomly divided into model group (Model): MRL / lpr group (n=6), treatment group: low-dose isoquercetin group (ISQ-L) (n=6), high-dose isoquercetin group (ISQ-H) (n=6), blank control group (Control): MRL / MPJ mice (n=6).

[0034] The MRL / lpr lupus model and control mice used in this experiment were purchased from Changzhou Cavens Laboratory Animal Co., Ltd. All animals were adaptively fed for 1 week before the experiment.

[0035] The urine protein and urine creatinine levels of mice in each group were detected using kits, the ratio of urine protein to urine creatinine was calculated, and the levels of blood creatinine (Cr), blood urea nitrogen (BUN) and anti-dsDNA and ANA were detected. PAS staining was used to detect the renal pathological changes of mice in each group. Immunofluorescence was used to detect the immune protein, complement deposition and macrophage infiltration in the kidneys of mice in each group.

[0036] Experimental Results

[0037] 1. The effect of isoquercetin on the general condition of lupus mice.

[0038] After 10 weeks of administration, there was no significant difference in body weight, kidney coefficient and spleen coefficient between the control group, model group and treatment group with low and high doses. Figure 2 a) Kidney coefficient ( Figure 2 b) and spleen coefficient ( Figure 2 c) No significant effect.

[0039] 2. Isoquercetin reduces the urine protein / urine creatinine ratio in lupus mice

[0040] In the late stage of systemic lupus erythematosus, lupus nephritis may occur, with severe proteinuria and increased urine protein / creatinine ratio. Compared with the model group, isoquercetin treatment significantly reduced the urine protein / creatinine ratio ( Figure 3 ).

[0041] 3. Isoquercetin reduces serum creatinine and blood urea nitrogen in lupus mice

[0042] Lupus nephritis is one of the more serious complications of systemic lupus erythematosus. Decreased renal function is one of the important manifestations of lupus nephritis, which may cause increased serum creatinine and blood urea nitrogen. After treatment with isoquercetin, serum creatinine ( Figure 4 a) Blood urea nitrogen ( Figure 4 b) Reduce.

[0043] 4. Isoquercetin reduces serum anti-dsDNA antibody levels

[0044] Elevated serum anti-dsDNA antibody levels are characteristic of systemic lupus erythematosus. The serum anti-dsDNA antibody and ANA antibody levels of lupus mice were significantly elevated. After treatment with isoquercetin, serum anti-dsDNA antibodies decreased significantly in a dose-dependent manner ( Figure 5 a), ANA levels decreased but without statistical difference ( Figure 5 b).

[0045] 5. Isoquercetin reduces renal mesangial cell proliferation and matrix accumulation

[0046] PAS staining results showed that compared with the control group ( Figure 6 a) Compared with the model group ( Figure 6 b) There were obvious injuries in the glomeruli, renal tubules and interstitium. The glomerular volume was significantly increased, the mesangial matrix was significantly increased, the renal tubules were regenerated and rearranged, and interstitial fibrosis occurred. Compared with the model group, after treatment with isoquercetin, the low and high dose groups ( Figure 6 c, d) Glomerular volume decreased, mesangial matrix accumulation decreased, tubular damage decreased, and interstitial fibrosis decreased.

[0047] 6. Isoquercetin reduces renal immune deposition in lupus mice

[0048] Immune complex and complement deposition are typical pathological manifestations of lupus nephritis. Immunofluorescence results showed that there was no obvious immune deposition in the control group, but there was obvious immune complex and complement deposition in the model group. After treatment with isoquercetin, kidney IgG( Figure 7 a) IgM Figure 7 c) and C3( Figure 7 e) The deposition was significantly reduced in a dose-dependent manner and was statistically significant ( Figure 7 b, d, f).

[0049] 7. Isoquercetin reduces macrophage infiltration in lupus mice

[0050] Lupus nephritis is a common complication of systemic lupus erythematosus involving the kidneys. Macrophages play an important role in the pathogenesis of lupus nephritis, and macrophage infiltration is an important manifestation of lupus nephritis. Immunofluorescence results showed that isoquercetin treatment can reduce macrophage infiltration in lupus mice ( Figure 8 a), and statistically significant ( Figure 8 b).

Claims

1. Use of isoquercetin in the preparation of a medicament for treating systemic lupus erythematosus.

2. The use according to claim 1, characterized in that The medicine also includes a pharmaceutically acceptable carrier and / or excipient.

3. The use according to claim 1, characterized in that The medicine is a pharmaceutical preparation that is administered by injection, oral administration, nasal mucosa, lung, rectum, oral mucosa or skin.

4. A drug for treating systemic lupus erythematosus, characterized in that: Contains a therapeutically effective amount of isoquercetin.

5. A drug for treating systemic lupus erythematosus according to claim 1, characterized in that: The medicine also includes a pharmaceutically acceptable carrier and / or excipient.

6. A drug for treating systemic lupus erythematosus according to claim 1, characterized in that: The medicine is a pharmaceutical preparation that is administered by injection, oral administration, nasal mucosa, lung, rectum, oral mucosa or skin.

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