Use of isorhamnetin in the preparation of a drug for preventing and treating male lower urinary tract symptoms / prostatofibrosis

Abstract

The application provides application of isorhamnetin in preparation of a drug for preventing and treating male lower urinary tract symptoms / prostatofibrosis. The application belongs to the technical field of biological medicine, and proves that isorhamnetin can effectively improve the prostatofibrosis level of db / db mice and relieve lower urinary tract symptoms through animal experiments, bioinformatics and network pharmacology methods, and isorhamnetin can play a role in improving prostatofibrosis by targeting PPAR gamma.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to the application of isorhamnetin in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis. Background Technology

[0002] Lower urinary tract symptoms (LUTS) are a common health problem in older men, typically manifesting as obstructive symptoms such as difficulty urinating and incomplete bladder emptying, as well as irritative symptoms such as urgency, dysuria, and nocturia. LUTS in middle-aged and older men is the result of multiple contributing factors, with current research suggesting that benign prostatic hyperplasia (BPH) is the most common cause of LUTS.

[0003] The main medications currently used to treat LUTS include 5α-reductase inhibitors and α1-receptor antagonists. 5α-reductase inhibitors specifically inhibit the conversion of testosterone to dihydrotestosterone by inhibiting 5α-reductase, thus alleviating clinical symptoms in LUTS patients. α1-receptor antagonists selectively block α1-adrenergic receptors on smooth muscle cells, relieving smooth muscle tension and alleviating clinical symptoms in LUTS patients. However, clinical practice has shown that approximately 30% of LUTS patients do not respond well to these two classes of medications and require surgical treatment. Recent studies have found that prostate fibrosis is an important pathological factor contributing to the worsening of LUTS symptoms and the poor efficacy of conventional medications. It can act as an independent or combined factor promoting the development of LUTS, but its exact mechanism of development remains unclear, and anti-fibrotic treatment has not yet been incorporated into LUTS treatment strategies.

[0004] Metabolic alterations are a crucial pathogenic mechanism in the development of fibrosis in various organs, and targeting metabolism holds promise as a novel therapeutic strategy for anti-fibrosis. Prostatic fibrosis is associated with lipid metabolism disorders; studies have reported that obesity induced by a high-fat diet can promote lower urinary tract fibrosis in mice. Patients with metabolic syndrome, especially those with hyperlipidemia, exhibit more severe prostatic fibrosis in their histopathological samples. Leptin receptor-deficient db / db mice, due to the loss of leptin receptor gene function leading to disruption of the leptin signaling pathway, spontaneously exhibit severe lipid metabolism disorders and have become a commonly used animal model for studying lipid metabolism abnormalities and related diseases.

[0005] Isorhamnetin (ISO) is a flavonoid compound widely found in natural plants such as prickly pear, sea buckthorn, ginkgo leaves, and Artemisia annua leaves. It possesses various pharmacological activities, including antioxidant, anti-inflammatory, anti-fibrotic, and glucose and lipid metabolism regulation. Chinese patent application CN 120938991 A discloses the application of isorhamnetin in the preparation of anti-myocardial fibrosis drugs, proposing that isorhamnetin can effectively reduce collagen deposition in myocardial tissue and effectively alleviate the increase in mRNA expression levels of myocardial fibrosis-related genes such as α-SMA, thus possessing the function of slowing down myocardial fibrosis.

[0006] Currently, there are no research reports on the use of isorhamnetin in the prevention and treatment of male LUTS / prostate fibrosis. Summary of the Invention

[0007] To enrich existing technologies, this invention provides the application of isorhamnetin in the preparation of drugs for the prevention and treatment of lower urinary tract symptoms / prostate fibrosis in men. Through animal and cell experiments, the inventors discovered that isorhamnetin, as the sole active ingredient, significantly downregulates prostate fibrosis levels in db / db mice, effectively improves urinary retention in the bladder, alleviates lower urinary tract symptoms, and simultaneously upregulates PPARγ expression. Based on bioinformatics combined with network pharmacology analysis, experiments verified that isorhamnetin can target PPARγ to exert its anti-prostate fibrosis effect. Based on the above findings, this invention is derived.

[0008] The objectives of this invention will be further explained by the following detailed description.

[0009] This invention provides the application of isorhamnetin in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis.

[0010] Preferably, isorhamnetin is the sole active ingredient.

[0011] Preferably, the isorhamnetin exerts its effect by targeting PPARγ.

[0012] Preferably, the male lower urinary tract symptoms / prostatic fibrosis are male lower urinary tract symptoms / prostatic fibrosis caused by lipid metabolism disorders.

[0013] Preferably, the male is a middle-aged or elderly male.

[0014] Preferably, the drug further includes pharmaceutically acceptable excipients. The drug may be formulated as tablets, capsules, or injections.

[0015] Compared with existing technologies, the beneficial effects of this invention include: Through animal and cell experiments, this invention demonstrates that isorhamnetin can effectively improve prostate fibrosis in db / db mice and alleviate lower urinary tract symptoms by downregulating the expression levels of fibrosis-related proteins α-SMA and Collagen I in the prostate tissue of db / db mice, reducing collagen fiber deposition in the prostate interstitium, and relieving urinary dribbling. Based on bioinformatics combined with network pharmacology analysis, experiments have verified that isorhamnetin can target PPARγ to exert its anti-prostate fibrosis effect. Furthermore, this invention provides the application of isorhamnetin in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis. This application broadens the application field of isorhamnetin and provides new ideas and candidate drugs for the clinical treatment of male lower urinary tract symptoms / prostate fibrosis. Attached Figure Description

[0016] Figure 1 Isorhamnetin relieves lower urinary tract obstruction and improves prostate fibrosis in db / db mice. (See figure for results).

[0017] Figure 2 Figure showing the mRNA and protein expression levels of prostate fibrosis-related factors (α-SMA, Collagen I) and PPARγ in each group of mice.

[0018] Figure 3 Results of screening for key targets of ISO in improving prostate fibrosis using bioinformatics combined with network pharmacology methods.

[0019] Figure 4 Molecular docking diagram of ISO with AKT1, MMP9, PPARG (PPARγ) and ESR1.

[0020] Figure 5 Figure showing the results of verifying the effect of isorhamnetin targeting PPARγ in improving prostate fibrosis. Detailed Implementation

[0021] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments.

[0022] In this invention, the experimental cells, reagents, and equipment involved are all commercially available products or can be obtained through conventional technical means in the field. In this invention, percentage content is understood in the usual sense within the industry; for example, 0.5% sodium carboxymethyl cellulose refers to mass-volume concentration, 4% paraformaldehyde refers to mass-volume concentration, and 10% fetal bovine serum refers to volume concentration. Example 1: Rhamnine improves prostatic fibrosis and regulates prostatic PPARγ expression in db / db mice.

[0023] 1. Experimental materials and instruments 1.1 Experimental Animals: Twenty-four 8-week-old SPF-grade male db / db mice (weighing 40-45 g) and eight control db / m mice (weighing 18-22 g) were purchased from Wuhan Hualianke Biotechnology Co., Ltd. The animal experiments were approved by the Experimental Animal Ethics Committee of Guizhou University (EAE-GZU-2025-T070).

[0024] 1.2 Major Instruments and Equipment: Real-time quantitative PCR instrument (Bio-Rad); WIX vertical electrophoresis tank and transfer tank (WIX Technologies); paraffin dehydrator and embedding machine (Wuhan Junjie Electronics Co., Ltd.); pathology slide machine (Shanghai Leica Instruments Co., Ltd.).

[0025] 1.3 Main experimental reagents: ISO (MedChemExpress, USA); rabbit anti-human α-smooth muscle actin (α-SMA) (Proteintech, China); mouse anti-human type I collagen (Collagen I) (Selleck, USA); rabbit anti-human PPARγ (Proteintech, China); HRP-labeled goat anti-rabbit / anti-mouse secondary antibody (Abcam, UK); RT-qPCR kit (Takara, Japan); primers for each gene were synthesized by Sangon Biotech (Shanghai) Co., Ltd.

[0026] 2. Experimental Methods 2.1 Animal grouping and model establishment ISO was diluted with 0.5% sodium carboxymethyl cellulose (CMC-Na) to form a suspension and stored at 4 ℃ for later use. After 1 week of acclimatization feeding, db / db and control db / m mice were randomly divided into 4 groups (n=8), and the grouping and treatment were as follows: (1) db / m group: db / m mice + 0.5% CMC-Na were administered by gavage for 1 month; (2) db / db group: db / db mice + 0.5% CMC-Na were administered by gavage for 1 month; (3) db / db + low dose ISO group (db / db+ISO-L): db / db mice + Gavage for 1 month; (4) db / db + ISO high-dose group (db / db+ISO-H): db / db mice + Mice were administered the medication by gavage for one month. After one month, the mice were sacrificed, and the urethra-prostate complex was collected from each group of mice to observe the urinary retention in the bladder. Prostate tissue was collected, with 3 mice used for prostate histopathological examination and 5 mice used for Western blot and RT-qPCR detection.

[0027] 2.2 HE and Masson staining Mouse prostate tissue was fixed with 4% paraformaldehyde for 48 h, routinely dehydrated, embedded in paraffin, and prepared into 4 μm sections. The sections were dewaxed to water, stained with hematoxylin for 5 min, differentiated with hydrochloric acid and ethanol, stained with eosin for 2 min, dehydrated and cleared, and then mounted with neutral resin. After dewaxing and hydration, the sections were stained with Masson's compound staining solution for 5 min, differentiated with phosphomolybdic acid, counterstained with aniline blue for 2 min, rapidly dehydrated, cleared, and mounted. The sections were observed under a light microscope and images were acquired. ImageJ software was used to analyze the percentage of the blue area (collagen-positive) around the acini in the images to assess the collagen content.

[0028] 2.3 Real-time quantitative PCR (RT-qPCR) RT-qPCR detection of prostate glands in mice of each group Acta2 (encoded α-SMA) Col1a1 (encoding collagen I) Ppar γ mRNA levels of the gene encoding PPARγ were determined. Total RNA was extracted from cells and mouse prostate tissue using the Trizol method, and its concentration and purity were measured. cDNA was then synthesized by reverse transcription according to the kit instructions. Real-time quantitative PCR was performed using GAPDH as an internal reference gene. Reaction conditions: 95 ℃ pre-denaturation for 30 s, 95 ℃ denaturation for 5 s, 60 ℃ annealing / extension for 30 s, for a total of 40 cycles. The relative expression level is calculated using this method.

[0029] 2.4 Western blot (WB) Total protein was extracted from prostate tissue of mice in each group, and protein concentration was determined using the BCA method. 30 μg of protein was subjected to SDS-PAGE electrophoresis and then transferred to a PVDF membrane. The membrane was blocked with 5% skim milk at room temperature for 1 h, and then incubated overnight at 4 °C with primary antibodies (α-SMA, Collagen I, PPARγ, and GAPDH, diluted 1:2000). The next day, HRP-labeled secondary antibody (1:10000) was added and incubated at room temperature for 1 h. The membrane was developed using ECL chemiluminescence reagent, and grayscale quantitative analysis was performed using ImageJ software. The relative expression level of the target protein was calculated using GAPDH as an internal control.

[0030] 2.5 Statistical Analysis of Data Data from each group are expressed as mean ± standard deviation (Mean ± SD). One-way ANOVA and t-tests were performed using SPSS version 20.0 software to determine whether statistically significant differences existed. p <0.05 indicates a statistically significant difference.

[0031] 3. Experimental Results ISO effectively alleviates urinary retention in the bladder and improves prostate fibrosis in db / db mice. (See figure for results). Figure 1 As shown; compared to the db / m group, Compared to db / db groups, ＃ express p <0.05, ＃＃ express p <0.01. Among them, Figure 1 -A represents the gross morphology of the urethra-prostate complex and the statistical results of bladder diameter in each group of mice; Figure 1 -B shows representative HE and Masson staining images and statistical results of prostate tissue from each group of mice. The mRNA and protein expression levels of prostate fibrosis-related factors (α-SMA, Collagen I) and PPARγ in each group of mice are shown below. Figure 2 As shown; compared to the db / m group, , Compared to db / db groups, ＃＃ express p <0.01. Among them, Figure 2 -A represents the RT-qPCR detection of prostate cancer in each group of mice. Acta2 (Encoding α-SMA protein) Col1a1 (encoding Collagen I protein) and Pparγ mRNA expression level of the gene (encoding PPARγ protein); Figure 2 -B represents the Western blot (WB) detection of α-SMA, Collagen I, and PPARγ protein expression levels in the prostate glands of mice in each group. For example... Figure 1 and Figure 2 As shown, compared with control db / db mice, db / db mice exhibited significant intravesical urinary retention. HE and Masson staining revealed thickening of the prostatic fibromuscular layer with periacinar fibrosis and collagen fiber deposition. Prostatic α-SMA and Collagen I expression were significantly increased, while PPARγ levels were significantly decreased. After one month of high-dose ISO intervention, intravesical urinary retention in db / db mice was effectively improved, and prostatic stromal fibrosis and collagen fiber deposition were reduced. Simultaneously, prostatic fibrosis markers (α-SMA, Collagen I) levels were downregulated, while PPARγ expression was upregulated. The low-dose ISO intervention group also showed the same trend. These results indicate that ISO can downregulate prostatic fibrosis levels in db / db mice, effectively improve lower urinary tract obstruction, and simultaneously upregulate PPARγ expression. Example 2: Screening for targets of ISO that improve prostate fibrosis using bioinformatics combined with network pharmacology methods.

[0032] 1. Experimental Methods Potential ISO targets were predicted and deduplicated using the Swiss TargetPrediction database (http: / / swisstargetprediction.ch / ) and the Similarity Ensemble Approach platform (https: / / sea.bkslab.org / ). Using "Prostatic Fibrosis" as the keyword, genes related to prostate fibrosis were retrieved from the GeneCards (https: / / www.genecards.org / ) and NCBI (https: / / www.ncbi.nlm.nih.gov / ) databases, and the intersection of these three databases was used to obtain intersection targets. Pathway enrichment analysis was performed on the intersection targets using the DAVID database (https: / / david.ncifcrf.gov / tools.jsp) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG). A p-value < 0.05 was used as the threshold to select statistically significant targets, and a bubble chart was plotted based on the enrichment analysis results. Intersecting target sites were imported into the STRING database (https: / / www.string-db.org / ), with the species limited to "Homosapiens," to obtain protein-protein interaction relationships. The obtained TSV-formatted interaction data was imported into Cytoscape software (version 3.2.0) to construct and visualize a PPI network. The topological parameters of each node in the network were calculated using Cytoscape's built-in Network Analyzer tool, and core regulatory proteins were screened based on their degree values. Subsequently, proteins with the highest degree rankings were selected as receptors for molecular docking, and the docking results were evaluated based on binding energy (ΔG, kcal / mol); lower binding energy indicates more stable binding.

[0033] 2. Experimental Results Bioinformatics combined with network pharmacology methods screened targets for ISO to improve prostate fibrosis. Results are as follows: Figure 3 As shown. Among them, Figure 3 -A is a Venn diagram showing the overlap between the predicted targets of ISO and genes related to prostate fibrosis. Figure 3 -B represents the KEGG enrichment analysis of 25 potential targets; Figure 3 -C represents a protein-protein interaction (PPI) network of 25 potential targets for ISO to improve prostate fibrosis. For example... Figure 3As shown, 25 genes were obtained by intersecting the predicted targets of ISO and prostate fibrosis-related genes in public databases. KEGG enrichment analysis showed that these genes were enriched not only in estrogen signaling pathways and inflammation-related pathways, but also significantly enriched in lipid metabolism regulatory pathways, such as insulin resistance signaling pathway, AMPK signaling pathway, and cAMPx signaling pathway, supporting the possibility that ISO's role in improving prostate fibrosis may be related to the regulation of lipid metabolism. PPI network analysis screened the top four core targets by degree ranking, namely AKT1, MMP9, PPARG (PPARγ), and ESR1. Further molecular docking experiments were conducted between ISO and AKT1, MMP9, PPARG (PPARγ), and ESR1, with results as shown below. Figure 4 As shown, molecular docking revealed that ISO had the lowest binding energy to PPARγ (-8.4 kcal / mol). These results suggest that PPARγ is likely a potential target for ISO to improve prostate fibrosis. Example 3: Isorhamnine targets PPARγ to improve prostate fibrosis.

[0034] 1. Experimental materials and instruments 1.1 Cell line: Human prostate stromal cells WPMY-1 were purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai). Cells were cultured in DMEM high-glucose medium (HyClone, USA) containing 10% fetal bovine serum (Gibco, USA) and 1% penicillin-streptomycin (Solarbio, China) at 37°C and 5% CO2.

[0035] 1.2 Main instruments and equipment: WIX vertical electrophoresis tank and transfer tank (WIX Technologies); rotating confocal microscope (OLYMPUS).

[0036] 1.3 Major experimental reagents: ISO (MedChemExpress, USA); recombinant human TGF-β1 (PeproTech, USA); rabbit anti-human α-smooth muscle actin (α-SMA) (Proteintech, China); mouse anti-human type I collagen (Collagen I) (Selleck, USA); rabbit anti-human PPARγ (Proteintech, China); HRP-labeled goat anti-rabbit / anti-mouse secondary antibody (Abcam, UK); 488 (anti-rabbit) and 594 (anti-mouse) fluorescently labeled secondary antibodies (Invitrogen, USA); PPARγ antagonist GW9662 (MedChemExpress, USA).

[0037] 2. Experimental Methods 2.1 Cell heat transfer assay (CETSA) WPMY-1 cells were seeded into two 10 cm dishes. After the cells reached confluence, they were washed three times with PBS and treated according to the following groups: (1) Control group (CON group): treated with normal medium containing 0.1% DMSO; (2) Isorhamnetin treatment group (ISO group): treated with medium containing 25 μmol·L⁻¹ PBS. - ¹ Treat with ISO culture medium for 2 h. After treatment, wash cells three times with PBS, gently scrape cells off on ice with a spatula and collect them into 15 mL centrifuge tubes. Centrifuge at 1000 rpm for 5 min, discard the supernatant, and retain the bottom cell cluster. Add 400 μL of PBS containing 10% protease inhibitor to the centrifuge tube, gently mix the cells, and then evenly distribute into six 1.5 mL centrifuge tubes. Incubate at room temperature for 3 min. Then place in a metal bath and heat at 40, 43, 46, 49, 52, and 55 °C for 3 min each. Immediately after heating, remove and let stand at room temperature for 3 min. Quickly freeze the sample in liquid nitrogen for 15 s, then thaw in a 25 °C water bath for 1 min. Gently shake the 1.5 mL centrifuge tubes to mix the liquid. Repeat this step three times. The sample was then centrifuged at 12,000 rpm and 4°C for 10 min. The supernatant was transferred to a new 1.5 mL centrifuge tube, and the appropriate volume of 5x protein loading buffer was added and mixed thoroughly. The sample was then placed in a metal bath and heated at 100°C for 10 min to denature the protein. The sample was stored at 4°C or -20°C for subsequent Western blot analysis.

[0038] 2.2 Establishment of a prostate fibrosis cell model and treatment with ISO and GW9662. WPMY-1 cells were seeded in 6-well plates (2.5 × 10⁻⁶ cells per well). 6 One hole -1 ) or a 24-well plate with climbing plates (5×10) 5 One hole -1 After the cell confluence reaches 70%-80%, the cells are treated according to the following groups: (1) Control group (CON group): normal culture medium treatment; (2) Model group (TGF-β1 group): treated with 10 ng·mL -1 TGF-β1 was used to treat the prostate fibrosis cell model for 24 h; (3) Model + isorhamnetin treatment group (TGF-β1 + ISO group): TGF-β1 was used to treat the prostate fibrosis cell model for 24 h; (4) Model + isorhamnetin treatment group (TGF-β1 + ISO group): TGF-β1 was used to treat the prostate fibrosis cell model for 24 h; (5) Model + isorhamnetin treatment group (T -1 TGF-β1 and 25 μmol·L -1 ISO culture medium treatment for 24 h; (4) Model + isorhamnetin + PPARγ inhibitor GW9662 treatment group (TGF-β1 + ISO + GW9662 group): pre-treated with 10 μmol·L -1After treatment with GW9662 for 1 h, add 10 ng·mL -1 TGF-β1 and 25 μmol·L -1 The cells were treated with ISO culture medium for 24 hours. After treatment, the cells were collected for immunofluorescence detection.

[0039] 2.3 Immunofluorescence Cells in each group were fixed with 4% paraformaldehyde for 20 min, washed with PBS, permeabilized with PBS containing 0.1% Triton X-100 for 10 min, and then blocked with 5% BSA for 30 min. Primary antibodies (α-SMA, Collagen I, or PPARγ, 1:1000) were added, and the cells were incubated at 4°C for 2 h. After washing three times with PBS (containing 0.1% Tween-20), fluorescent secondary antibodies (anti-rabbit 488 or anti-mouse 594) were added, and the cells were incubated at room temperature in the dark for 30 min. Cells were mounted with DAPI and observed and photographed under a fluorescence microscope. Fluorescence intensity was analyzed using ImageJ software. Each group had three replicates, and the experiment was repeated three times.

[0040] 2.5 Statistical Analysis of Data Data from each group are expressed as mean ± standard deviation (Mean ± SD). One-way ANOVA and t-tests were performed using SPSS version 20.0 software to determine whether statistically significant differences existed. p <0.05 indicates a statistically significant difference.

[0041] 3. Experimental Results Isorhamnetin targets PPARγ to improve prostate fibrosis, as shown in the following results. Figure 5 As shown; compared to group CON, express p <0.01, compared with the TGF-β1 group, ＃ express p <0.05, ＃＃ express p <0.01. Among them, Figure 5 -A represents the thermal stability of PPARγ in WPMY-1 cells as detected by CETSA method; Figure 5 -B is the thermal melting curve of PPARγ in WPMY-1 cells obtained based on CETSA; Figure 5 -C represents the immunofluorescence staining used to detect the protein expression levels of PPARγ, α-SMA, and Collagen I in WPMY-1 cells of each group. For example... Figure 5As shown in the CETSA results, the thermal stability of PPARγ in WPMY-1 cells changed significantly after ISO treatment. The thermal melting curves obtained by CETSA showed that, compared with the control group, the protein survival rate of PPARγ in the ISO-treated group was significantly increased at different temperature gradients, confirming the interaction between ISO and PPARγ. Further treatment with the PPARγ antagonist GW9662 was used to observe its effect on ISO in improving prostate fibrosis. The results showed that TGF-β1 treatment upregulated the expression of α-SMA and Collagen I, and downregulated the expression of PPARγ in WPMY-1 cells; ISO intervention resulted in downregulation of α-SMA and Collagen I expression and upregulation of PPARγ expression; while GW9662 treatment reversed the ameliorative effect of ISO on prostate fibrosis. These results indicate that ISO can exert its anti-prostate fibrosis effect by regulating PPARγ.

[0042] This invention, from a holistic experimental perspective, utilizes animal experiments, bioinformatics combined with network pharmacology methods, and cell experiments. Employing various experimental methods including HE staining, Masson trichrome staining, Western blotting, RT-qPCR, CETSA, and immunofluorescence staining, it was found that isorhamnetin effectively improves prostate fibrosis in db / db mice by downregulating the expression levels of fibrosis-related proteins α-SMA and Collagen I in prostate tissue, reducing collagen fiber deposition in the prostate interstitium, and alleviating urinary dribbling. This also shows that isorhamnetin can improve prostate fibrosis by targeting PPARγ.

[0043] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. The application of isorhamnetin in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis.

2. The use of isorhamnetin according to claim 1 in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis, characterized in that: Isorhamnetin is the sole active ingredient.

3. The use of isorhamnetin according to claim 1 or 2 in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis, characterized in that: The isorhamnetin works by targeting PPARγ.

4. The use of isorhamnetin according to claim 1 or 2 in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis, characterized in that: The aforementioned male lower urinary tract symptoms / prostate fibrosis are caused by lipid metabolism disorders.

5. The use of isorhamnetin according to claim 1 or 2 in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis, characterized in that: The man in question is a middle-aged or elderly man.

6. The use of isorhamnetin according to claim 1 or 2 in the preparation of drugs for the prevention and treatment of male lower urinary tract symptoms / prostate fibrosis, characterized in that: The drug also includes pharmaceutically acceptable excipients.

Images