Application of cycloastragenol in preparation of product for treating male sexual dysfunction

Abstract

The invention discloses application of cycloastragenol in preparation of a product for treating male sexual dysfunction, and relates to the technical field of biological medicine, sexual dysfunction of male mice caused by high-fat diet, medicine and aging is remarkably improved through intervention of cycloastragenol, the specific expression is that changes of body weight and testis weight are controlled, and the sexual dysfunction of the male mice caused by high-fat diet, medicine and aging is improved. The sperm motility rate is obviously improved, the hormone release level of testosterone and gonadotropin is increased, and the testicular tissue structure is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to the application of cycloastragenol in preparing a product for treating male sexual dysfunction. Background Art

[0002] Male sexual activity, encompassing sexual desire, erection, intercourse, ejaculation, and orgasm, is a complex physiological process. When any of these processes are disrupted and affect normal sexual function, it is considered male sexual dysfunction, manifesting as symptoms such as sexual desire disorder (HS), erectile dysfunction (ED), premature ejaculation (PE), and oligospermia. Current research indicates that the main causes of male sexual dysfunction are aging and obesity. Statistics show that the incidence of male sexual dysfunction is increasing annually worldwide, making it a global reproductive health issue. However, the exact pathogenesis of male sexual dysfunction remains unclear, and treatment options are relatively limited. Currently, conventional treatments include surgery and hormonal medications. However, these approaches have limitations and risks. For example, surgery requires a long recovery and treatment period, is costly, and can be accompanied by pain and sequelae, requiring a period of recovery. Hormonal therapy can cause hormonal imbalances and other side effects, and long-term use can also adversely affect health. Therefore, the discovery of natural compounds that can effectively treat male sexual dysfunction is crucial.

[0003] Astragalus membranaceus is widely cultivated throughout China and is a commonly used traditional Chinese medicine. Cycloastragenol (CA), a natural compound, is highly lipid-soluble, easily permeates cell membranes, and is readily absorbed by the body. Studies have shown that cycloastragenol can enhance telomerase activity and exhibit antioxidant and anti-aging effects. Therefore, cycloastragenol may have a positive effect on improving sexual dysfunction caused by aging and obesity. Therefore, further research into the mechanism of action of CA is needed to provide new solutions for male reproductive health. Summary of the Invention

[0004] The purpose of the present invention is to provide an application of cycloastragenol in the preparation of a product for treating male sexual dysfunction, so as to solve the problems raised in the prior art.

[0005] To achieve the above object, the present invention provides the following technical solutions: Application of cycloastragenol in the preparation of products for treating male sexual dysfunction.

[0006] Application of cycloastragenol in the preparation of products for treating male sexual dysfunction induced by a high-fat diet.

[0007] Furthermore, the manifestations induced by the high-fat diet include any one or more of the following: weight change, testis weight change, decreased sperm count, decreased sperm concentration, decreased sperm motility, decreased serum testosterone, increased follicle-stimulating hormone, decreased gonadotropin-releasing hormone, and testicular tissue structure and morphological changes.

[0008] Application of cyclocophorol in the preparation of products for treating drug-induced male sexual dysfunction.

[0009] Furthermore, the manifestations induced by the drug include any one or more of the following: weight change, testis weight change, decreased sperm count, decreased sperm concentration, decreased sperm motility, decreased serum testosterone, increased follicle-stimulating hormone, decreased gonadotropin-releasing hormone, and testicular tissue structure and morphological changes.

[0010] Application of cyclocophorol in the preparation of products for treating male sexual dysfunction caused by aging.

[0011] Furthermore, the manifestations of sexual dysfunction caused by aging include any one or more of the following: weight change, testis weight change, decreased sperm count, decreased sperm concentration, decreased sperm motility, decreased serum testosterone, increased follicle-stimulating hormone, decreased gonadotropin-releasing hormone, and testicular tissue structure and morphological changes.

[0012] Furthermore, the symptom manifestations of male sexual dysfunction include any one or more of the following: sexual desire disorder, erectile dysfunction, premature ejaculation, and oligoasthenospermia.

[0013] Furthermore, the dosage of cyclocophorol in the preparation of products for treating male sexual dysfunction is 30 - 300 mg / d; the products include capsules, tablets, and powders.

[0014] The present invention realizes the use of cyclocophorol in the preparation of products for treating male sexual dysfunction through the following technical solutions: Set up 3 independent animal experiment protocols: (1) High-fat diet protocol: 36 six-week-old specific pathogen-free C57BL / 6J male mice were divided into 3 groups according to the random number table method; they were the blank group, the high-fat diet group, and the medicated group, with 12 mice in each group.

[0015] (2) CTX protocol: 36 six-week-old specific pathogen-free C57BL / 6J male mice were divided into 3 groups according to the random number table method, namely the blank group, the CTX group, and the medicated group, with 12 mice in each group. Among them, CTX is cyclophosphamide.

[0016] (3)Aging protocol: Twenty-four 52-week-old specific pathogen-free C57BL / 6J male mice were randomly divided into two groups, namely the aging blank group and the aging drug-treated group, with 12 mice in each group; Twenty-four 6-week-old specific pathogen-free C57BL / 6J male mice were randomly divided into two groups, namely the young blank group and the young drug-treated group, with 12 mice in each group.

[0017] 2. Evaluate the reproductive function indexes of mice in each group: (1)Measure the body weight and testicular weight of mice in each group, and calculate the testicular organ coefficient (organ coefficient = organ mass / body weight × 100%) to evaluate the relative development of reproductive organs; (2)Use an automatic sperm counter to detect the number and motility of epididymal sperm to evaluate sperm production and quality; (3)Observe the testicular tissue morphology by HE staining to evaluate the integrity and changes of tissue structure; (4)Determine the levels of serum testosterone (T), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) by ELISA to understand the changes in hormone levels; Compared with the prior art, the beneficial effects of the present invention are as follows: 1. Through the intervention of cyclocophorol, the present invention significantly improves the sexual dysfunction of male mice induced by a high-fat diet, specifically manifested as the control of changes in body weight and testicular weight, a significant increase in sperm motility rate, an increase in the levels of testosterone and gonadotropin-releasing hormone, and an improvement in testicular tissue structure.

[0018] 2. The technical solution of the present invention can increase the level of testosterone in the serum of aging male mice, and the weights of the testis and epididymis increase significantly. Compared with the model group, the sperm concentration and quantity of aging male mice also increase significantly after the administration ends.

[0019] 3. Through the treatment of cyclocophorol, the present invention can effectively improve the symptoms of oligospermia and asthenospermia in mice caused by cyclophosphamide, specifically manifested as a significant increase in sperm quantity, concentration, and motility, an increase in the levels of testosterone and gonadotropin-releasing hormone in the serum, and a significant increase in the weights of the testis and epididymis.

[0020] 4. The present invention not only effectively evaluates the beneficial effects of cyclocophorol on sexual dysfunction in obese and aging male mice, but also truly and objectively describes the therapeutic effect of cyclocophorol on sexual dysfunction in male mice caused by drugs such as cyclophosphamide, and provides scientific basis and experimental data for this, laying a foundation for subsequent research and application. Description of the Drawings

[0021] Figure 1 It is a chart showing the growth of epididymal weight in mice of each group; Figure 2 Chart showing the testicular weight gain of mice in each group; Figure 3 Chart showing the sperm count, concentration, and sperm motility of mice in each group; Figure 4 Chart showing the levels of serum testosterone (T), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) in mice in each group; Figure 5 Schematic diagram of the testicular tissue morphology of mice in each group. Detailed implementation manners

[0022] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the protection scope of the present invention.

[0023] In the following embodiments, the males are 6-week-old wild-type C57BL / 6 male mice, purchased from Beijing Sparf Bioscience Co., Ltd., with a body weight of about 20-22 g. The males are 52-week-old wild-type C57BL / 6 male mice, purchased from Beijing Sparf Bioscience Co., Ltd., with a body weight of about 20-22 g. All male mice are raised in Jiangsu Hanjiang Biotechnology Co., Ltd., with an environmental temperature of 22±2°C, a humidity of 55±10%, and a 12-hour day-night light cycle. The experimental protocol has been approved by the animal ethics committee of this hospital. The high-fat diet formula model: D12492, purchased from Research Diets. Cycloastragenol is purchased from Jiangsu Yongjian Medical Technology Co., Ltd.

[0024] Example 1: High-fat diet protocol: The experimental protocol includes the following steps: Thirty-six 6-week-old specific pathogen-free C57BL / 6J male mice were divided into 3 groups by the random number table method, namely the blank group, the high-fat diet group, and the medication group, with 12 mice in each group. The mice in the high-fat diet group and the medication group were fed with a high-fat diet, and the mice in the blank group were fed with a normal maintenance diet for 10 weeks. In the 11th week, drugs were administered according to the group for 8 weeks, and the mice were fed in the same way as before during the drug administration period; among them, the administration dose of cycloastragenol was 1 mg per kilogram of body weight for male mice.

[0025] Example 2: CTX protocol: The experimental protocol includes the following steps: Thirty-six 6-week-old specific pathogen-free C57BL / 6J male mice were randomly divided into 3 groups by the random number table method, namely the blank group, the CTX group and the medicated group, with 12 mice in each group. All groups were fed with ordinary maintenance feed. During the experiment of the CTX group, in the 11th week, the blank group was intraperitoneally injected with normal saline, and the CTX group and the medicated group were intraperitoneally injected with cyclophosphamide at a dose of 60 mg / kg body weight once a day for 5 consecutive days. From the 6th day of the 11th week, gavage administration was carried out according to the group. The 6th day was regarded as the first day of administration, for a total of 8 weeks. Among them, the administration dose of astragaloside was 1 mg per kilogram of body weight of male mice.

[0026] Example 3: Aging protocol: The experimental protocol includes the following steps: Twenty-four 52-week-old specific pathogen-free C57BL / 6J male mice were randomly divided into 2 groups by the random number table method, namely the aging blank group and the aging medicated group, with 12 mice in each group; Twenty-four 6-week-old specific pathogen-free C57BL / 6J male mice were randomly divided into 2 groups by the random number table method, namely the young blank group and the young medicated group, with 12 mice in each group. All groups were fed with ordinary maintenance feed. Administration was carried out for 8 weeks, and the administration dose of astragaloside was 1 mg per kilogram of body weight of male mice.

[0027] The setting schemes of the above Examples 1-3 are independent of each other.

[0028] Detection method: 1. Determination of testicular and epididymal organ coefficients All mice were weighed, sacrificed by exsanguination from the eye socket, and then the testicular and epididymal tissues were removed and weighed using an electronic scale. The organ coefficient was calculated as the ratio of the testicular and epididymal mass to the body mass, that is, organ coefficient = organ mass / body mass × 100%.

[0029] 2. Staining analysis of mouse testicular pathological sections Testicular tissues of each group of mice were collected, fixed in 4% paraformaldehyde for 24 h, dehydrated with gradient ethanol, cleared with xylene, embedded in paraffin and sectioned, stained with hematoxylin-eosin staining method, and then observed and photographed under a microscope for analysis.

[0030] 3. Detection of serum biochemical indexes Each group of mice was anesthetized and blood was taken from the eye socket. The blood was allowed to stand at 4 °C for 2 h, centrifuged at 4000 r / min for 10 min, the serum of each group of mice was collected, and the levels of serum testosterone (T), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH) were measured by ELISA.

[0031] 4. Semen quality detection The bilateral epididymides of each group of mice were removed and transferred to a centrifuge tube containing 2 mL of normal saline, minced with tissue scissors, incubated in a 37°C constant temperature water bath for 10 min to fully dissociate the sperm, filtered to prepare a sperm suspension, and the sperm concentration, quantity, and motility were detected using a Myron automatic sperm analysis system. The data of each sample were recorded and statistically analyzed.

[0032] 5. Data Statistics and Analysis The ONE-WAY ANOVA test was used for normally distributed data with GraphPad software. P < 0.05 indicates a difference, P < 0.01 indicates a significant difference, and P < 0.001 indicates an extremely significant difference.

[0033] The experimental results are as Figures 1 - 5 shown; Conclusion: The experimental results show that through the intervention of cyclocophorol, the present invention significantly improves the sexual dysfunction of male mice induced by high-fat diet, aging, and drugs. Specifically, the changes in body weight and testis weight are controlled, the sperm motility rate is significantly increased, the levels of testosterone and gonadotropin-releasing hormone are elevated, and the testicular tissue structure is improved.

[0034] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-restrictive. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present invention. Any reference signs in the claims should not be regarded as limiting the claimed rights.

Claims

1. Application of cycloastragenol in the preparation of products for treating male sexual dysfunction.

2. Application of cycloastragenol in the preparation of products for treating male sexual dysfunction induced by high-fat diet.

3. The application according to claim 2, wherein: The manifestations induced by high-fat diet include any one or more of the following: body weight change, testicular weight change, decrease in sperm count, decrease in sperm concentration, decrease in sperm motility, decrease in serum testosterone, increase in follicle-stimulating hormone, decrease in gonadotropin-releasing hormone, and change in testicular tissue structure and morphology.

4. Application of cycloastragenol in the preparation of products for treating male sexual dysfunction induced by drugs.

5. The application according to claim 4, characterized in that: The manifestations induced by drugs include any one or more of the following: body weight change, testicular weight change, decrease in sperm count, decrease in sperm concentration, decrease in sperm motility, decrease in serum testosterone, increase in follicle-stimulating hormone, decrease in gonadotropin-releasing hormone, and change in testicular tissue structure and morphology.

6. Application of cycloastragenol in the preparation of products for treating male sexual dysfunction caused by aging.

7. The application according to claim 6, characterized in that: The manifestations of sexual dysfunction caused by aging include any one or more of the following: body weight change, testicular weight change, decrease in sperm count, decrease in sperm concentration, decrease in sperm motility, decrease in serum testosterone, increase in follicle-stimulating hormone, decrease in gonadotropin-releasing hormone, and change in testicular tissue structure and morphology.

8. The application according to any one of claims 1, characterized in that: The symptoms of male sexual dysfunction include any one or more of the following: sexual desire disorder, erectile dysfunction, premature ejaculation, and oligoasthenospermia.

9. The application according to any one of claims 1, characterized in that: The dosage of cycloastragenol in the preparation of products for treating male sexual dysfunction is 30 - 300 mg / d; the products include capsules, tablets, and powders.

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