Application of rotenone compound in preparation of medicine for treating psoriasis

Abstract

The invention discloses an application of rotenone compounds in preparation of drugs for treating psoriasis. After related cells are incubated by rotenone and derris in vitro, immunoblotting analysis is carried out, and the result shows that the rotenone and derris can regulate and control the expression of STAT3 and AMPK signal related proteins. In a mouse psoriasis model induced by an in-vivo imiquimod (Imiquimod, IMQ) cream, the external administration of rotenone and derris can significantly reduce scale, erythema and skin thickness, and can inhibit the proliferation of epithelial echinocyte. Therefore, the compound can be used as an active component for regulating an STAT3 signal channel to prepare a medicine for treating an autoimmune disease-psoriasis, and meanwhile, the medicine can activate an AMPK signal channel, so that the compound also has huge potential in the aspects of resisting tumors and metabolic diseases.

Description

Technical Field

[0001] The invention belongs to the field of autoimmune disease treatment, and specifically relates to the application of rotenone compounds in the preparation of drugs for treating psoriasis. Background Art

[0002] Psoriasis is a chronic inflammatory disease of the skin that affects 2%-3% of the population worldwide. Psoriasis vulgaris is the most common clinical subtype, accounting for approximately 85% of cases, and is characterized by thick, erythematous plaques covered by silvery lamellar scales that are preferentially localized to the extensor surfaces, scalp, and trunk. Other less common clinical subtypes include pustular, maculopapular, palmoplantar, erythrodermic, and inverse psoriasis. Psoriasis can present as a relatively mild form with a limited number of lesions to a more severe form in which more than 10% of the skin surface is affected. Approximately one-third of patients will develop psoriatic arthritis. In addition, comorbidities of psoriasis include cardiometabolic disorders, stroke, metabolic syndrome, chronic kidney disease, mood disorders, and lymphoma, which can lead to a decrease in the patient's overall life expectancy. Therefore, psoriasis is not only a skin disease but also a systemic inflammatory disease.

[0003] Psoriasis is considered a T-cell-mediated autoimmune disease influenced by genetic susceptibility and environmental stimuli such as trauma, infection, and drugs. Genome-wide association studies (GWAS) of psoriasis-associated genes have shown that susceptibility to the disease involves both the adaptive and innate immune systems. The pathogenesis of psoriasis is associated with activation of dendritic cells residing in the dermis by epidermal antigens released by skin trauma or infection. Activated dendritic cells feedback upregulate the production of IFN-α and -β, TNF-α, IL-6, and IL-23. IL-6 plays a fundamental role in the differentiation of T lymphocytes into Th17 cells, which are generally considered to play a central role in the pathogenesis of psoriasis. The effects of IL-6 on naive T cells include the induction of STAT3 (Signal Transducer and Activator of Transcription 3)-dependent IL-23 receptors, which in turn is essential for conferring IL-23 responsiveness and full effector function to Th17 cells. In addition, resident γδ T cells, a population that expands in the dermis of patients with psoriasis, have also been shown to produce IL-17 and participate in the pathogenesis of the disease. Other effector cytokines include GM-CSF, TNF, IL-21, IL-22, IL-26, and IL-29. Together, these cytokines stimulate the formation and maintenance of psoriatic plaques, which are characterized by excessive proliferation and abnormal differentiation of keratinocytes, with keratinocyte nuclei retained in the uppermost differentiated epidermal layer (parakeratosis), including the expression of the specific psoriasis autoantigen Krt17 (K17) in epidermal keratinocytes, and promote the recruitment of leukocytes to damaged skin.

[0004] Psoriasis cannot be cured and is prone to recurrence. The purpose of treatment is to control the disease, slow down or inhibit the progression of the disease, reduce clinical manifestations such as skin lesions, control related complications and improve the quality of life of patients. Lifelong treatment is required and personalized treatment plans are advocated. According to my country's 2022 Primary Diagnosis and Treatment Guidelines for Psoriasis, mild psoriasis is mainly treated with skin care products and topical medications such as emollients and glucocorticoids. Moderate patients are mainly treated with systemic treatment, including retinoids, immunosuppressants, biological agents and phototherapy, and are assisted by topical medications and skin care products. Severe patients are mainly treated with systemic treatment, including retinoids, immunosuppressants, biological agents and phototherapy, and are assisted by topical medications and skin care products. Acitretin capsules are a type of drug that belongs to the class of retinoids and are derivatives of vitamin A. However, the use of acitretin to treat psoriasis has side effects such as teratogenicity, increased blood lipids, and adverse reactions to the skin and mucous membranes, and it also has a certain impact on bones. The side effect of the immunosuppressant methotrexate is that it can cause abnormal liver and kidney function. Clinically, for psoriasis vulgaris, including plaque psoriasis, acitretin capsules can be selected, while for severe psoriasis, methotrexate can be selected. Drugs can improve the condition faster or improve the efficacy, but adverse reactions such as skin infections should be closely observed. Combined ultraviolet light therapy can improve the efficacy, but combined ultraviolet light increases the risk of skin cancer.

[0005] Tofacitinib is an oral JAK1 and 3 inhibitor that has been approved for rheumatoid arthritis (RA) and is currently being evaluated for the treatment of plaque psoriasis and psoriatic arthritis. However, RA patients treated with tofacitinib have an increased risk of pulmonary embolism and overall mortality. Ruxolitinib is a JAK1 and JAK1-2 inhibitor. In a phase 2 trial of patients with localized psoriasis (less than 20% of body surface area affected), the efficacy of ruxolitinib was not significantly increased. In a phase 1 clinical trial, Ruxolitinib was shown to be safe, well tolerated, and showed significant clinical activity in the topical treatment of psoriasis. However, the duration of the study was relatively short and the sample size was small.

[0006] Rotenone and deguelin are a new type of isoflavones isolated from natural plants. This type of substance can bind to mitochondrial respiratory chain complex 1, thereby inhibiting mitochondrial oxidative phosphorylation and is one of the important components of pesticides. However, recent studies have also shown that rotenone and deguelin can inhibit STAT3-related signaling pathways to regulate the body's related pathological and physiological processes. IL-6 / STAT3 plays a vital role in the pathogenesis of psoriasis. The low expression of p-STAT3 (705) and p-STAT3 (727) and the reduction of related inflammatory factors can maintain the body's immune homeostasis and improve the degree of inflammation in patients with autoimmune diseases such as psoriasis, showing the application of this substance in the development of drugs against autoimmune diseases such as psoriasis. At the same time, this drug can also activate the AMPK signaling pathway, which is closely related to tumor development and metabolic diseases. Therefore, it also has great potential in anti-tumor and anti-metabolic diseases. Summary of the invention

[0007] The purpose of the present invention is to provide an application of a rotenone compound in the preparation of a drug for treating psoriasis.

[0008] Based on the above purpose, the present invention adopts the following technical solutions: The invention discloses an application of a rotenone compound in the preparation of a drug for treating psoriasis. The rotenone compound is one or a mixture of any proportion of rotenone, deguelin, dehydrorotenone, rotendione and biologically acceptable salts thereof.

[0009] Furthermore, the biologically acceptable salt refers to a biologically acceptable salt formed by rotenone, rotenin, dehydrorotenone or rotendione with at least one of acetic acid, dihydrofolic acid, benzoic acid, citric acid, sorbic acid, propionic acid, oxalic acid, fumaric acid, maleic acid, hydrochloric acid, malic acid, phosphoric acid, diphosphoric acid, hydrobromic acid, nitric acid, sulfurous acid, sulfuric acid, vanillic acid, tartaric acid, succinic acid, ascorbic acid, boric acid, lactic acid, p-toluenesulfonic acid, salicylic acid and ethylenediaminetetraacetic acid.

[0010] The medicine is prepared from one or a mixture of any proportion of rotenone, detenone, dehydrorotenone, rotenonedione and biologically acceptable salts thereof into injection, tablets, powder injection, granules, capsules, oral liquid, ointment or cream.

[0011] A rotenone or deguelin ointment is prepared by melting a prescribed amount of white vaseline at 50-70°C, dissolving the rotenone or deguelin in an appropriate amount of anhydrous ethanol, and then dripping the ethanol solution of the rotenone or deguelin into the white vaseline, continuing to stir for 15-45 minutes, and placing at 0-10°C for 15-45 minutes to obtain a semisolid ointment. The mass concentration of the rotenone or deguelin (i.e., the rotenone or deguelin accounts for the total weight) is 0.05-0.07%. The rotenone or deguelin ointment can be applied to the skin for the treatment of psoriasis.

[0012] The administration method of the pharmaceutical composition of the present invention is not particularly limited, and representative administration methods include (but are not limited to): oral, rectal, parenteral (intravenous, intramuscular or subcutaneous) and topical administration.

[0013] The composition of the present invention can be administered alone or in combination with other pharmaceutically acceptable compounds (such as anti-autoimmune disease drugs).

[0014] The psoriasis described herein refers to psoriasis vulgaris, pustular psoriasis, macular psoriasis, palmoplantar psoriasis, erythrodermic psoriasis, inverse psoriasis and arthritis psoriasis, as well as other autoimmune diseases associated with psoriasis.

[0015] The invention relates to an application of a rotenone compound in the preparation of a STAT3 protein phosphorylation inhibitor, wherein the rotenone compound is a mixture of one or more of rotenone, deguelin, dehydrorotenone, rotendione and biologically acceptable salts thereof in any proportion. The drug is used to treat autoimmune diseases such as ulcerative colitis, rheumatoid arthritis, etc.

[0016] The application of rotenone compounds in the preparation of AMPK protein agonists, wherein the rotenone compounds are one or a mixture of any proportion of rotenone, deguelin, dehydrorotenone, rotendione and biologically acceptable salts thereof. The drug is used to treat tumors and metabolic diseases such as obesity, non-alcoholic fatty liver disease, and diabetes.

[0017] Specifically, the present invention relates to the application of rotenone, deguelin, dehydrorotenone and rotenone. The evaluation of the therapeutic effect on the psoriasis mouse model shows that such compounds have good anti-inflammatory effects on the psoriasis mouse model. The exploration of the pharmacodynamic mechanism of such compounds is found to have great potential in anti-tumor and anti-metabolic disease.

[0018] In summary, the present invention provides the use and potential molecular mechanism of rotenone and rotenin in the treatment of psoriasis and other autoimmune diseases, as well as the use and potential molecular mechanism of rotenone and rotenin in the treatment of tumors and metabolic diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is the compound structural formula of rotenone and deguelin; Figure 2 The immunoblotting results show that rotenone and deguelin inhibit the expression of proteins in STAT3-related signaling pathways; Figure 3 The results of immunoblotting show that rotenone and deguelin activate the expression of proteins in the AMPK-related signaling pathway; Figure 4 This is a gross morphological observation of the therapeutic effects of rotenone and deguelin on the psoriasis mouse model; Figure 5 To observe the skin histology of psoriasis mouse models treated with rotenone and deguelin; Figure 6 PASI score (scaly) and statistical analysis of skin lesions in the psoriasis mouse model treated with rotenone and deguelin; Figure 7 PASI score (erythema) and statistical analysis of skin lesions in psoriasis mouse model treated with rotenone and deguelin; Figure 8 To provide the PASI score (thickness) and statistical analysis of skin lesions in the psoriasis mouse model treated with rotenone and deguelin; Fig. 9 The PASI score (comprehensive score) and statistical analysis of skin lesions in the psoriasis mouse model treated with rotenone and deguelin. DETAILED DESCRIPTION

[0020] In order to make the technical purpose, technical solution and beneficial effects of the present invention more clear, the technical solution of the present invention is further described below in conjunction with the accompanying drawings and specific embodiments.

[0021] Example 1. Preparation process of rotenone and deguelin smear preparations Process: Place the prescribed amount of white vaseline in a 10mL beaker, and melt the white vaseline in a 60℃ water bath to a nearly transparent liquid. Place the prescribed amount of rotenone or deguelin and anhydrous ethanol in a 1.5mL EP tube, and ultrasonicate until clarified. Then, add them dropwise into the beaker at a speed of 1000r / min. Continue stirring for 30min, and place in a 4℃ refrigerator. After half an hour, a semi-solid ointment can be obtained.

[0022] Example 2: Effects of rotenone and deguelin on the expression of STAT3-related signaling pathway proteins and AMPK-related signaling pathway proteins in MDA-MB-468 cells 1. Cell culture and drug addition: a. Take MDA-MB-468 cells in the logarithmic growth phase and adjust the density to 2×10 52 mL of cell suspension was inoculated into each well of a 6-well plate at 37°C and 5% CO 2 Incubate overnight in an incubator, add different concentrations of rotenone and deguelin to make the final concentrations 0, 10, 100, 300, 1000 nM), DMSO as a negative control. c. After culturing for 24 hours, lyse the cells with RIPA lysis buffer and collect the protein.

[0023] 2. Cell collection and lysis: a. Discard the upper culture medium and wash the cells twice with pre-cooled PBS. Add 100 μL of pre-cooled RIPA cell lysis buffer (protease inhibitors and PMSF are added to the lysis buffer in a ratio of 1:100 and mixed in advance) to each well.

[0024] b. Lyse on ice for 3 min, scrape the cells with a cell scraper and collect them into a 1.5 mL EP tube; place on ice for 30 min and vortex every 6 min.

[0025] c. Centrifuge at 4°C, 12,000 g for 10 min. Transfer the cell supernatant to a new EP tube.

[0026] d. Divide the cell supernatant into two parts: take 5 μL and add it to a 1.5 mL EP tube for BCA protein content measurement, and then add Add 45 μL of 1× PBS and mix well for later use; take 80 μL of the remaining cell supernatant, add 20 μL of 5× SDS Loading Buffer, mix well and boil in boiling water for 10 min, centrifuge and load on the sample or store in a -20℃ refrigerator.

[0027] e. Protein concentration determination steps: (1) Preparation of BCA working solution: Calculate the total amount of mixed working solution of A and B required based on the number of standards and samples to be tested. Prepare the working solution at a volume ratio of 50:1 between BCA solid reagent A and B, vortex and mix well for later use.

[0028] (2) 1× PBS diluted protein standard: (3) Take 25 μL of each of the protein standard solution and the sample supernatant diluted with PBS (10-fold dilution) and add them to a new 96-well plate. Then add 200 μL of the pre-prepared BCA working solution and mix thoroughly. Be careful not to blow and create bubbles. Cover the 96-well plate tightly and react in a 37°C incubator for 30 min.

[0029] (4) Take out the 96-well plate and return it to room temperature for 3-5 minutes. Measure the absorbance value of A562 on an ELISA reader and save the obtained value in an Excel table. Make a standard curve and calculate the protein content of 1 μL of each sample for protein loading.

[0030] 3. SDS-PAGE: (1) Fix the gel plate and prepare 10% SDS-PAGE separation gel.

[0031] Prepare separation gel according to the following table: 10 mL (2) Add the mixed separation gel to two gel plates, add to the position 1.0 cm from the top, fill the gel plates with anhydrous ethanol, and let it stand for 30-45 minutes. (3) After the separation gel is solidified, pour out the remaining anhydrous ethanol and absorb the remaining anhydrous ethanol with filter paper. (4) Prepare 5 mL of 5% concentrated gel according to the table below (5) Slowly add the prepared concentrated glue to the glue plate to avoid generating bubbles, insert a comb, and let it stand for 30 to 45 minutes.

[0032] (6) Take out the protein sample, heat it in a water bath at 100 °C for 5 min, and centrifuge it at 10,000 rpm for 5 min. (7) Fix the gel plate to the electrophoresis tank, add SDS-PAGE electrophoresis buffer, pull out the comb, and add the processed protein samples to the sample tank in order, with 50 µg of protein per well. (8) Electrophoresis at 80 V for 40 min. (9) Change the voltage to 120 V and perform electrophoresis for about 1.5 h until bromophenol blue runs out of the colloid; IV. Western-blot: (1) Rinse the SDS-PAGE gel after electrophoresis in TBST buffer once, and soak the protein gel in transfer buffer. (2) Soak a layer of cotton pad in membrane transfer buffer, clamp it onto the transfer machine with tweezers, and place it in the order of blackboard, cotton pad, filter paper, protein gel, PVDF membrane, filter paper, cotton pad and white board, clamp it, and put it into the transfer machine. If there are bubbles between each layer, use a glass tube to gently roll them out. (3) Turn on the transfer machine and transfer at a constant current of 300 mA for 80 min. (4) Place the membrane in TBST buffer and rinse 3 times, 8 min each time. (5) Block with 20 mL of 5% BSA-TBST blocking solution at room temperature for 2 h. (6) Add primary antibody and incubate overnight at 4℃ 60 rpm. (7) Wash the membrane three times with TBST at room temperature, shaking on a 60 rpm platform, for 10 min each time. (8) Add secondary antibody and incubate at room temperature for 1 h. (9) Wash the membrane three times with TBST at room temperature, shaking at 60 rpm, for 10 min each time. (10) Take 1 mL each of chemiluminescent substrate solution A and solution B and develop color at room temperature for 2 min. (11) Use filter paper to absorb the liquid on the membrane and expose it to light.

[0033] 5. Reagent preparation: (1) 10% SDS: Weigh 1 g of high-purity (electrophoresis grade) SDS into a 10 mL centrifuge tube, add about 8 mL of deionized water, heat to dissolve, dilute to 10 mL, and store at room temperature.

[0034] (2) 10% ammonium persulfate (AP): Weigh 1 g of ammonium persulfate, add about 10 mL of deionized water, stir to dissolve, and store at 4°C.

[0035] (3) 5× electrophoresis buffer: Weigh 15.1 g Tris, 94 g Glycine, and 5.0 g SDS into a beaker, add 1 L of double distilled water to dissolve, store at room temperature, and dilute 5 times before use.

[0036] (4) Transfer buffer: Weigh 5.8 g Tris, 11.6 g glycine, and 0.75 g SDS into a beaker, add 700 mL of double distilled water, dissolve and adjust the volume to 800 mL, and finally add 200 mL of methanol.

[0037] (5) 1.5 mol / L Tris-HCl, 100 mL: Dissolve 18.15 g Tris in 80 mL water and adjust the pH to 8.8 with 4 N HCl. Make up to 100 mL.

[0038] (6) 0.5 mol / L Tris-HCl, 1000 mL: Weigh 60.5 g of Tris base, add water to 850 mL, add concentrated hydrochloric acid and stir until completely dissolved, then adjust the pH to 6.8 and add water to 1 L.

[0039] (7) TBS buffer: Weigh 8.8 g of NaCl in 800 mL of distilled water, dissolve it, add 10 mL of 1 mol / L Tris HCl (pH 7.5), make up to 1 L, and store at room temperature.

[0040] (8) TBST buffer: Add 500 μL of 20% Tween 20 to 1L TBS buffer to make the final concentration of Tween 20 0.1%. Prepare it before use.

[0041] (9) Blocking solution, antibody diluent: Add 5% skimmed milk powder or BSA to TBST buffer and prepare it before use.

[0042] like Figure 2 The results showed that 100nM, 300nM and 1000nM rotenone and deguelin treatment can effectively inhibit the expression levels of P-STAT3 (705) and P-STAT3 (705) in related cells. This result indicates that rotenone and deguelin have the potential to treat certain diseases such as autoimmune diseases-psoriasis by inhibiting the expression of STAT3-related proteins.

[0043] like Figure 3 The results showed that 100nM rotenone and deguelin treatment can effectively activate the phosphorylation of acetyl-CoA carboxylase (P-ACC) and the expression of P-AMPK in related cells. This result shows that rotenone and deguelin have the function of regulating the body's energy metabolism, fat synthesis and oxidative energy supply, thereby treating tumors and metabolic diseases such as obesity, non-alcoholic fatty liver disease, and diabetes.

[0044] Example 3. Gross morphological observation of the therapeutic effects of rotenone and deguelin on psoriasis mouse model The experimental animals were 10-week-old female Balb / c mice purchased from Sibeifu (Beijing) Biotechnology Co., Ltd. and kept in an SPF animal laboratory. After the mice were adapted for 1 week, the backs were shaved 2-3 days in advance and randomly divided into five groups: normal mouse blank control group (n=5), the back lesion area was externally applied with white vaseline preparation once a day, 62.5 mg each time. Model control group (IMQ group, n=5): 5% imiquimod cream was applied to the back lesion area once a day, 62.5 mg each time; 62.5 mg, white vaseline was applied to the back of the mice after an interval of 8 hours, once a day. Positive control drug group (methotrexate solution 1mg / kg / IMQ group, n=5): methotrexate solution with a drug concentration of 1 mg / kg was given intragastrically once a day, 0.1 mL each time, and 62.5 mg, 5% imiquimod cream was applied to the back lesion area once a day. Experimental group: 62.5 mg, 5% imiquimod cream was applied to the back lesion area once a day, and 62.5 mg of 0.064% (n=5) rotenone paste or 62.5 mg of 0.064% rotenone paste (n=5) was applied to the same part once a day after an interval of 8 hours. After 8 consecutive days of treatment, the mice were killed, and the back skin and subcutaneous tissue were collected and fixed in a pre-prepared fixative (10% paraformaldehyde) for 24 hours for HE staining and immunohistochemistry.

[0045] The results are as follows Figure 4 As shown in the results, compared with the normal group, the IMQ-induced skin lesions in the model control group showed typical psoriasis features including erythema, scaling, thickening and scaly skin lesions. The positive control drug methotrexate solution (Methotrexate 1mg / kg) and rotenone (Rotenone 0.064%) and deguelin (Deguelin 0.064%) treatment groups significantly inhibited these skin lesions, showing only slight calloused skin and a small amount of scales.

[0046] Example 4: Rotenone and deguelin inhibit IMQ-induced mouse epithelial cell proliferation The fixed mouse skin tissue was dehydrated, waxed, paraffin-embedded, sliced, and attached to a slide, and baked at 60 °C for 3 h. The slices were then placed in xylene I for 10 min, xylene II for 10 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, 95% alcohol for 5 min, 90% alcohol for 5 min, 80% alcohol for 5 min, 70% alcohol for 5 min, and washed with distilled water for 5 min for dewaxing and hydration. The slices were stained with Harris hematoxylin for 3 min, washed with tap water, differentiated with 1% hydrochloric acid alcohol for a few seconds, rinsed with tap water, blued with 0.6% ammonia water, and rinsed with running water. The slices were stained with eosin stain for 3 min. The slices were placed in 95% alcohol I for 5 min, 95% alcohol II for 5 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, xylene I for 5 min, and xylene II for 5 min to dehydrate and make them transparent. The slices were taken out of xylene and slightly dried, and sealed with neutral gum. Observation and image acquisition and analysis were performed under an Olympus pathology microscope.

[0047] The results are as follows Figure 5 As shown, compared with the epidermis of the normal (blank control) group of mice, under the continuous stimulation of IMQ, the stratum corneum of the epithelium of the model control (IMQ) group of mice was significantly thickened and broken, and the prickle cells (keratinocytes) proliferated and formed large papillae extending to the subcutaneous tissue. The epithelial layer of mice in the methotrexate treatment group (Methotrexate 1mg / kg) and rotenone (Rotenone0.064%) and deguelin (Deguelin 0.064%) treatment groups was significantly thinned, and the epithelial thickness of the deguelin treatment group was close to that of the normal group of mice. This result shows that rotenone and deguelin can inhibit IMQ-induced mouse epithelial cell proliferation.

[0048] Example 5: Rotenone and deguelin significantly reduce the PASI score of psoriasis mice The damaged areas of the back skin of each group of mice were scored using the scoring website http: / / pasi.corti.li / , and the psoriasis score was calculated based on the proportion of psoriasis lesion area, redness (0-4), thickening (0-4), and severity of scaling symptoms (0-4) in the lesion area. Figure 6-9 The results showed that IMQ can induce severe scaling, erythema and thickening of mouse skin, and the PASI scores and comprehensive scores are very high. Methotrexate (IMQ+MTX 1mg / kg) can relieve various symptoms, and rotenone (IMQ+ Rotenone-0.064%) and deguelin (IMQ+ Deguelin-0.064%) are better than methotrexate in relieving various symptoms and PASI scores.

[0049] The above results show that rotenone and deguelin have good inhibitory effects on imiquimod-induced keratinocyte proliferation and lipid metabolism disorders, and can effectively downregulate the expression levels of p-STAT3 (Y705) and p-STAT3 (S727). Therefore, this type of drug shows good application prospects in the treatment of psoriasis.

[0050] At the same time, this type of compound can also activate AMPK phosphorylation, so this type of compound also has great application potential in anti-tumor and metabolic diseases (such as obesity and non-alcoholic fatty liver disease).

[0051] According to the general approach of drug development (conventional anti-inflammatory in vitro screening first, then targeted research), the compounds of the present invention can be applied to the treatment of autoimmune diseases closely related to inflammation, and can be prepared as anti-autoimmune disease drugs by mixing with human-acceptable salts or with pharmaceutical carriers.

[0052] According to the general approach of drug development (conventional anti-tumor and anti-metabolic disease in vitro screening first, and then targeted research), the compounds of the present invention can be applied to cancer treatment drugs related to abnormal cell proliferation, and can be prepared as anti-tumor drugs and metabolic disease drugs by mixing with human-acceptable salts or with pharmaceutical carriers.

[0053] Finally, it should be noted that the above embodiments are only used to illustrate but not limit the technical solutions of the present invention, and any equivalent substitutions of the present invention and any modifications or partial substitutions that do not depart from the spirit and scope of the present invention should be included in the scope of protection of the claims of the present invention.

Claims

1. The use of rotenone compounds in the preparation of drugs for treating psoriasis, characterized in that: The rotenone compound is one of rotenone, detenin, dehydrorotenone, rotenone and biologically acceptable salts thereof, or a mixture of two or more thereof in any proportion.

2. The use according to claim 1, characterized in that: The biologically acceptable salt refers to a biologically acceptable salt formed by rotenone, rotenin, dehydrorotenone or rotendione with at least one of acetic acid, dihydrofolic acid, benzoic acid, citric acid, sorbic acid, propionic acid, oxalic acid, fumaric acid, maleic acid, hydrochloric acid, malic acid, phosphoric acid, diphosphoric acid, hydrobromic acid, nitric acid, sulfurous acid, sulfuric acid, vanillic acid, tartaric acid, succinic acid, ascorbic acid, boric acid, lactic acid, p-toluenesulfonic acid, salicylic acid and ethylenediaminetetraacetic acid.

3. The use according to claim 1, characterized in that: The medicine is prepared from one or a mixture of any proportion of rotenone, detenone, dehydrorotenone, rotenonedione and biologically acceptable salts thereof into injection, tablets, powder injection, granules, capsules, oral liquid, ointment or cream.

4. The use according to claim 1, characterized in that: The rotenone compound is administered alone or in combination with other pharmaceutically acceptable drugs.

5. Use of rotenone compounds in the preparation of STAT3 protein phosphorylation inhibitors, characterized in that: The rotenone compound is one of rotenone, detenin, dehydrorotenone, rotenone and biologically acceptable salts thereof, or a mixture of two or more thereof in any proportion.

6. The use of rotenone compounds in the preparation of AMPK protein agonists, characterized in that: The rotenone compound is one of rotenone, detenin, dehydrorotenone, rotenone and biologically acceptable salts thereof, or a mixture of two or more thereof in any proportion.

7. Use of rotenone compounds in the preparation of drugs for treating tumors, obesity, non-alcoholic fatty liver disease and diabetes, characterized in that: The rotenone compound is one of rotenone, detenin, dehydrorotenone, rotenone and biologically acceptable salts thereof, or a mixture of two or more thereof in any proportion.

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