Application of methyl 4-hydroxycinnamate and ester thereof
By modifying methyl 4-hydroxycinnamate and its C2-C10 esters to improve bioavailability, the problem of the inability of existing technologies to effectively treat male oligospermia and asthenospermia has been solved, and the effects of significantly increasing sperm count and motility and improving testicular tissue have been achieved.
Patent Information
- Application Number
- CN202411084063.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-07
- Publication Date
- 2026-02-10
AI Technical Summary
There is a lack of effective drugs for treating male oligospermia and asthenospermia in the current technology, especially drugs that cannot significantly increase sperm count and sperm motility.
Using methyl 4-hydroxycinnamate and its C2-C10 esters, by improving its hydrophobicity to enhance bioavailability and promote cell membrane penetration, a drug to improve male reproductive capacity was prepared.
It significantly increased sperm count and sperm motility in mice with oligoasthenospermia, improved pathological damage to testicular tissue, reduced inflammatory factor levels, and upregulated antioxidant factor expression.
Smart Images
Figure CN121489928A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, and in particular to the application of methyl 4-hydroxycinnamate and its esterified products. Background Technology
[0002] Male infertility is often caused by oligospermia and asthenospermia, with low sperm count and poor sperm motility being the most important factors. Currently, the causes of oligospermia and asthenospermia are complex and diverse, including diseases (such as diabetes), pathogen infections, genetic defects, environmental pollutants, and radiation exposure, all of which are important contributing factors.
[0003] There is currently no specific drug for treating oligospermia and asthenospermia; treatment generally involves dietary therapy, traditional Chinese medicine, and other methods. Summary of the Invention
[0004] In view of this, the present invention provides an application of methyl 4-hydroxycinnamate and its esterified products, which can significantly increase the sperm count and sperm motility in mice with oligoasthenospermia.
[0005] Hydroxycinnamic acid (HCA) is a plant phenolic acid widely found in grains, fruits, and vegetables. It has been extensively studied for its anti-inflammatory, antioxidant, antibacterial, antitumor, and antiplatelet aggregation effects. However, because its main functional group for antioxidant activity is the phenolic hydroxyl group, it is easily oxidized, leading to low bioavailability, low stability, and rapid metabolism, resulting in pharmacokinetic problems. Furthermore, the dissociation effect of the carboxylic acid group makes it difficult to penetrate cell membranes, limiting its biological activity. Therefore, modifying HCA to increase its hydrophobicity and promote cell membrane penetration is of great significance for prolonging drug efficacy, improving bioavailability, and enhancing biological activity.
[0006] Methyl 4-hydroxycinnamate (KS-3) is an esterified derivative of 4-hydroxycinnamic acid, found in the roots, stems, and leaves of various medicinal plants. KS-3 has been shown to exhibit anti-inflammatory and antioxidant properties; however, current technology has not disclosed its role in preventing or treating oligospermia or asthenospermia.
[0007] The applicant has improved the bioavailability of KS-3 and its C2-C10 esters by synthesizing and administering them, thereby increasing sperm count and sperm motility in mice with oligoasthenospermia. Based on this, this application provides the use of the compound shown in formula (I) in the preparation of a drug for improving male fertility:
[0008]
[0009] Wherein, R is selected from H or R1-CO-, and R1 is selected from C2 to C10 alkyl groups.
[0010] The compound shown in formula (I) is methyl 4-hydroxycinnamate and its esterified derivatives. When R is H, it is methyl 4-hydroxycinnamate, and when R is R1-CO-, it is an esterified derivative of methyl 4-hydroxycinnamate.
[0011] In some specific implementations, R1 is selected from C2 to C10 alkyl groups, including straight-chain alkyl groups and branched-chain alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, isobutyl, nonyl, decyl, etc., preferably n-butyl, n-pentyl, n-hexyl, and n-heptyl.
[0012] In some specific implementations, the compound shown in formula (I) is KS-3, which is methyl 4-hydroxycinnamate, with the following structural formula:
[0013]
[0014] The compound shown in formula (I) is methyl 4-hydroxycinnamate butyrate, with the following structural formula:
[0015]
[0016] The compound shown in formula (I) is methyl valerate of 4-hydroxycinnamate, with the following structural formula:
[0017]
[0018] The compound shown in formula (I) is methyl 4-hydroxycinnamate hexanoate, with the following structural formula:
[0019]
[0020] The compound shown in formula (I) is methyl 4-hydroxycinnamate heptanoate, with the following structural formula:
[0021]
[0022] This application does not impose any special restrictions on the source of the compound shown in formula (I). It can be purchased directly from the market or prepared according to the method disclosed in patent CN117550978A.
[0023] The compounds provided in this application can be used to prepare drugs that improve male fertility, specifically, to enhance male fertility or improve male fertility impairment. In some specific implementations, male fertility impairment can be caused by pollutants, such as microplastics or plasticizers; diseases, such as diabetes; or drugs, such as commonly used drugs like sodium valerate. Experiments have shown that the above causes can all lead to oligospermia and asthenospermia in mice, and the compounds provided in this application have an ameliorative effect on male fertility impairment caused by various reasons. In some specific implementations, the male can be a human, mouse, rat, or rabbit, etc.
[0024] In some specific implementations, the improvement of male reproductive capacity includes the prevention and treatment of oligoasthenospermia and / or the protection of testicular tissue. Specifically, the prevention and treatment of oligoasthenospermia includes increasing sperm count and / or improving sperm motility. Experimental results show that the compounds provided in this application can significantly increase sperm count and improve sperm motility in mice with oligoasthenospermia. The protection of testicular tissue includes improving tissue morphology, reducing inflammatory factor levels, and upregulating antioxidant factor levels, or one or more of these. Improving tissue morphology includes improving seminiferous tubule arrangement and improving spermatocyte atrophy. Inflammatory factors include interleukin-1β and / or tumor necrosis factor; the antioxidant factor is NAD(P)H quinone dehydrogenase 1. Experimental results show that the compounds provided in this application significantly downregulate the expression of the inflammatory genes IL-1β and TNF-α and upregulate the expression of the antioxidant gene NQO-1 in mice with oligoasthenospermia.
[0025] This application constructs three models of oligoasthenospermia in Kunming mice: one induced by nanoplastics (PSNPs) and a plasticizer (DEHP) induced by streptozotocin (STZ), and another induced by antiepileptic drugs. The effects of the compound shown in formula (I) on improving male reproductive capacity were verified through sperm count analysis, sperm motility analysis, analysis of mRNA expression levels of inflammation and antioxidant genes, and analysis of testicular tissue pathological damage. Experimental results show that the compound shown in formula (I) increased sperm count and motility in oligoasthenospermia mice, improved testicular tissue pathological damage, inhibited the expression of inflammatory factors, and increased the expression of antioxidant genes, demonstrating significant potential in the treatment of oligoasthenospermia. Attached Figure Description
[0026] Figure 1 The results show the weight statistics of the mice in Experiment Example 1;
[0027] Figure 2 The results of sperm count statistics in mice in Experiment Example 1;
[0028] Figure 3 The statistical results of sperm motility in mice in Experiment Example 1;
[0029] Figure 4 The results of the weight statistics of the mice in Experiment Example 2;
[0030] Figure 5 The results of sperm count statistics in mice in Experiment Example 2;
[0031] Figure 6 The statistical results of sperm motility in mice in Experiment Example 2;
[0032] Figure 7 The statistical results of interleukin-1β (IL-1β) expression levels in mice in Experiment Example 2;
[0033] Figure 8 The statistical results of tumor necrosis factor (TNF-α) expression levels in mice in Experiment Example 2;
[0034] Figure 9 The statistical results of NAD(P)H quinone dehydrogenase 1 (NQO-1) expression in mice in Experiment Example 2;
[0035] Figure 10 This is a stained image of a mouse tissue section from Experimental Example 2;
[0036] Figure 11 The weight statistics of the mice in Experiment 3;
[0037] Figure 12 The results of sperm count statistics in mice in Experiment Example 3;
[0038] Figure 13 The statistical results of sperm motility in mice in Experiment Example 3;
[0039] Figure 14 The statistical results of interleukin-1β (IL-1β) expression levels in mice in Experiment Example 3;
[0040] Figure 15 The statistical results of tumor necrosis factor (TNF-α) expression levels in mice in Experiment Example 3;
[0041] Figure 16 The statistical results of NAD(P)H quinone dehydrogenase 1 (NQO-1) expression in mice in Experiment Example 3;
[0042] Figure 17 This is a stained image of a tissue section from mouse case 3 in Experimental Example 3;
[0043] Figure 18 The weight statistics of the mice in Experiment 4;
[0044] Figure 19The results of sperm count statistics in mice in Experiment Example 4;
[0045] Figure 20 The statistical results of sperm motility in mice in Experiment Example 4;
[0046] Figure 21 The results of sperm count statistics in mice in Experiment Example 5;
[0047] Figure 22 The statistical results of sperm motility in mice in Experiment Example 5;
[0048] Figure 23 The statistical results are for the forward sperm motility of mice in Experiment 5. Detailed Implementation
[0049] It should be understood that the expression “one or more of…” individually includes each of the objects described after the expression, as well as various different combinations of two or more of the described objects, unless otherwise understood from the context and usage. The expression “and / or” combined with three or more described objects should be understood to have the same meaning, unless otherwise understood from the context.
[0050] The terms “including,” “having,” or “containing,” including the use of their grammatical synonyms, should generally be understood as open-ended and non-restrictive, for example, not excluding other unstated elements or steps, unless otherwise specifically stated or understood from the context.
[0051] It should be understood that the order of the steps or the order in which certain actions are performed is not important as long as the invention remains operational. Furthermore, two or more steps or actions can be performed simultaneously.
[0052] The use of any and all instances or exemplary language such as “e.g.” or “including” in this document is merely intended to better illustrate the invention and is not intended to limit the scope of the invention unless the claims are made. No language in this specification should be construed as indicating that any unclaimed element is essential to the practice of the invention.
[0053] Furthermore, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values in the specific embodiments have been presented as precisely as possible. However, any value inevitably contains standard deviations due to individual test methods. Therefore, unless explicitly stated otherwise, it should be understood that all ranges, quantities, values, and percentages used in this disclosure are modified with the word "approximately." Here, "approximately" generally means an actual value within plus or minus 10%, 5%, 1%, or 0.5% of a particular value or range.
[0054] This application provides the use of the compound shown in formula (I) in the preparation of a drug for improving male fertility:
[0055]
[0056] Wherein, R is selected from H or R1-CO-, and R1 is selected from C2 to C10 alkyl groups.
[0057] This application constructs three models of oligoasthenospermia in Kunming mice: one induced by nanoplastics (PSNPs) and a plasticizer (DEHP) induced by streptozotocin (STZ), and another induced by antiepileptic drugs. The effects of the compound shown in formula (I) on improving male reproductive capacity were verified through sperm count analysis, sperm motility analysis, analysis of mRNA expression levels of inflammation and antioxidant genes, and analysis of testicular tissue pathological damage. Experimental results show that the compound shown in formula (I) increased sperm count and motility in oligoasthenospermia mice, improved testicular tissue pathological damage, inhibited the expression of inflammatory factors, and increased the expression of antioxidant genes, demonstrating significant potential in the treatment of oligoasthenospermia.
[0058] The following examples further illustrate the application of methyl 4-hydroxycinnamate and its esters provided in this application.
[0059] In the following examples, the compounds can be purchased commercially or prepared using methods well known to those skilled in the art.
[0060] KS-3 is methyl 4-hydroxycinnamate, with the following structural formula, and is available for purchase on the market:
[0061]
[0062] 4-Hydroxycinnamate methyl butyrate, with the following structural formula, can be prepared according to the method disclosed in patent CN117550978A:
[0063]
[0064] 4-Hydroxycinnamate methyl valerate, with the following structural formula, can be prepared according to the method disclosed in patent CN117550978A:
[0065]
[0066] 4-Hydroxycinnamate methyl hexanoate, with the following structural formula, can be prepared according to the method disclosed in patent CN117550978A:
[0067]
[0068] The structural formula of methyl 4-hydroxycinnamate heptanoate is as follows, and it can be prepared according to the method disclosed in patent CN117550978A:
[0069]
[0070] The structural formula of resveratrol butyrate is as follows, and it can be prepared according to the method disclosed in patent CN117550978A:
[0071]
[0072] The structural formula of resveratrol valerate is as follows, and it can be prepared according to the method disclosed in patent CN117550978A:
[0073]
[0074] The methods for evaluating sperm count and sperm motility in the following experimental examples are as follows:
[0075] After collecting epididymal samples, they were chopped and placed in a 24-well plate. 1000 μL of PBS was added, and the plate was incubated at 37°C for 10 minutes. After incubation, the sample was filtered, and 10 μL of the filtrate was added to a cell counting chamber. Sperm count and motility were analyzed using a sperm analyzer.
[0076] The steps involved in the mRNA generation of inflammation and antioxidant genes in testicular tissue are as follows:
[0077] The expression of relevant inflammatory factors and antioxidant genes in testicular tissue was determined by qPCR, including interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and NAD(P)H quinone dehydrogenase 1 (NQO1).
[0078] The histological analysis is as follows:
[0079] Collected testicular tissue samples were fixed with freshly prepared 4% paraformaldehyde and then stained with hematoxylin and eosin (H&E). Specifically, paraffin sections of testicular tissue were baked in an oven at 65°C for at least 1.5 hours to ensure the paraffin on the tissue sections was fully melted. The sections were then placed twice in xylene to remove the melted paraffin and dehydrated in a gradient of ethanol. The sections were stained sequentially with hematoxylin and eosin, followed by dehydration with ethanol. After staining, the sections were clarified twice in xylene and fixed with neutral resin. The stained sections were then scanned for observation.
[0080] Experimental Example 1
[0081] (1) Laboratory animals
[0082] Eight-week-old male KM mice were fed at a room temperature maintained at 23±1℃ and a humidity maintained at 50±10%. They were kept in a 12-hour light-dark cycle and had free access to clean food and water.
[0083] (2) Experimental methods
[0084] Sixty KM mice were randomly divided into four groups: Control group, Model group, Resveratrol Butyrate + Model group, Resveratrol Valerate + Model group, KS-3 Butyrate + Model group, and KS-3 Valerate + Model group, with 10 mice in each group. Except for the Control group, each mouse was administered 200 μL of nanoplastics (PSNPs) (0.75 mg / ml) and 200 μL of the plasticizer di(2-ethylhexyl) phthalate (DEHP) (60 mg / ml) by gavage daily to construct an environmental pollutant-induced oligoasthenospermia. The Resveratrol Butyrate + Model group, Resveratrol Valerate + Model group, KS-3 Butyrate + Model group, and KS-3 Valerate + Model group were simultaneously administered 200 μL of the corresponding drug (15 mM) by gavage daily. The Control group was administered corn oil by gavage as a control. The KM mice were weighed and their data were recorded at the same time each day before gavage. On day 28, tissue samples were collected, and the epididymis was used for sperm counting and sperm motility testing.
[0085] (3) Experimental Results
[0086] Data are expressed as mean ± standard deviation (SEM). *P<0.05; **P<0.01; ***P<0.001. The independent samples t-test was used to assess the differences between the two groups. All graphs were generated using GraphPad Prism 8.0.
[0087] See Figure 1 , Figure 2 and Figure 3 , Figure 1 The results show the weight statistics of the mice in Experiment 1. Figure 2 The results show the sperm count of the mice in Experiment 1. Figure 3 This presents the statistical results of sperm motility in mice from Experiment Example 1. Figure 1 , Figure 2 and Figure 3It was found that, except for the resveratrol valerate + Model group, there were no significant changes in mouse body weight in other groups; the sperm count of mice in each treatment group did not change significantly; the Model group significantly reduced sperm motility, indicating successful establishment of the oligoasthenospermia mouse model; compared with the Model group, the KS-3 butyrate + Model group, KS-3 valerate + Model group, and resveratrol valerate + Model group significantly increased sperm motility in oligoasthenospermia mice. Therefore, KS-3 butyrate, KS-3 valerate, and resveratrol valerate can increase sperm motility in mice with oligoasthenospermia induced by PSNPs + DEHP.
[0088] Experimental Example 2
[0089] The difference from Experimental Example 1 is that the experimental method is as follows:
[0090] Forty KM mice were randomly divided into four groups: Control group, Model group, KS-3 valerate + Model group, and KS-3 valerate group, with 10 mice in each group. In the Model group and KS-3 valerate + Model group, each mouse was administered 200 μL of PSNPs (1.5 mg / ml) and 200 μL of DEHP (120 mg / ml) by gavage every two days to induce environmental pollutant-induced oligoasthenospermia. Simultaneously, the KS-3 valerate + Model group was treated with KS-3 valerate (30 mM) by gavage every two days. The Control group received corn oil by gavage as a control. The KS-3 valerate group was treated with KS-3 valerate (30 mM) by gavage every two days. Tissue samples were collected on day 40. Epididymis was used for sperm counting and motility testing, and testis was used for histological molecular analysis and analysis of inflammation and antioxidant gene mRNA. Results are shown below. Figure 4 , Figure 5 , Figure 6 , Figure 7 , Figure 8 , Figure 9 and Figure 10 , Figure 4 The results show the weight statistics of the mice in Experiment 2. Figure 5 The results of sperm count statistics in mice in Experiment Example 2 are as follows. Figure 6 The results show the statistical findings of sperm motility in mice in Experiment Example 2. Figure 7 The above are the statistical results of interleukin-1β (IL-1β) expression levels in mice in Experiment Example 2. Figure 8 The above are the statistical results of tumor necrosis factor (TNF-α) expression levels in mice in Experiment Example 2. Figure 9 The results show the statistical analysis of NAD(P)H quinone dehydrogenase 1 (NQO-1) expression levels in mice in Experiment Example 2. Figure 10 This is a stained image of a mouse tissue section from Experimental Example 2. (From...) Figure 4 , Figure 5 and Figure 6It was found that there were no significant changes in the body weight of mice in any group; the Model group significantly reduced sperm count and sperm motility, indicating successful establishment of the oligoasthenospermia mouse model; compared with the Model group, the KS-3 valerate + Model group and the KS-3 valerate significantly increased sperm count and sperm motility in oligoasthenospermia mice. Therefore, KS-3 valerate can improve oligoasthenospermia by increasing sperm count and sperm motility. Figure 7 , Figure 8 and Figure 9 It was found that the Model group significantly upregulated the expression of inflammatory genes IL-1β and TNF-α and downregulated the expression of the antioxidant gene NQO-1. The mRNA expression levels of NQO1, IL-1β, and TNF-α in the testes of mice in the KS-3 valerate + Model group were significantly different from those in the Model group. Therefore, KS-3 valerate supplementation can significantly reduce testicular inflammation and increase antioxidant mRNA expression in PSNPs + DEHP-induced oligoasthenospermia mice (P < 0.05). Figure 10 It can be seen that the Model group caused disordered seminiferous tubule arrangement and spermatocyte atrophy and damage, while KS-3-valerate can effectively alleviate this condition, indicating that KS-3-valerate can improve testicular pathological damage in oligoasthenospermia mice.
[0091] Experimental Example 3
[0092] The difference from Experimental Example 1 is that the experimental method is as follows:
[0093] Forty KM mice were randomly divided into four groups: Control, Model, Model+KS-3, Model+KS-3 butyrate, and Model+KS-3 valerate, with eight mice in each group. Except for the Control group, all groups except the Control group were injected with streptozotocin (STZ) (80 mg / kg) on days 1 and 2 to induce diabetic oligoasthenospermia. Fasting blood glucose was used as evidence of successful model establishment. Simultaneously, the Model+KS-3, Model+KS-3 butyrate, and Model+KS-3 valerate groups were administered KS-3 (15 mM), KS-3 butyrate (15 mM), and KS-3 valerate (15 mM) by gavage daily, respectively. The Control group received corn oil via gavage as a control. On day 17, STZ (120 mg / kg) was injected to prolong the model period. Tissue samples were collected on day 34. Epididymis was used for sperm counting and motility testing, and testes were used for histological molecular analysis and mRNA analysis of inflammation and antioxidant genes.
[0094] See results Figure 11 , Figure 12 , Figure 13 , Figure 14 , Figure 15 , Figure 16 and Figure 17 , Figure 11 The results show the weight statistics of the mice in Experiment 3. Figure 12 The results of sperm count statistics in mice in Experiment 3 are as follows. Figure 13 The results show the statistical findings of sperm motility in mice in Experiment 3. Figure 14 The above are the statistical results of interleukin-1β (IL-1β) expression levels in mice in Experiment 3. Figure 15 The results show the statistical effects of tumor necrosis factor (TNF-α) expression levels in mice in Experiment 3. Figure 16 The results show the statistical analysis of NAD(P)H quinone dehydrogenase 1 (NQO-1) expression levels in mice in Experiment Example 3. Figure 17 This is a stained image of a mouse tissue section from Experimental Example 3.
[0095] Depend on Figure 11 , Figure 12 and Figure 13 It was found that KS-3, KS-3 butyrate, and KS-3 valerate all increased the body weight of mice; the Model group significantly reduced sperm count and sperm motility, indicating successful establishment of the oligoasthenospermia mouse model; compared to the Model group, the KS-3 butyrate + Model group and the KS-3 valerate + Model group significantly increased sperm count and sperm motility in oligoasthenospermia mice, while the KS-3 + Model group significantly increased sperm count. Therefore, KS-3, KS-3 butyrate, and KS-3 valerate can improve oligoasthenospermia by increasing sperm count and sperm motility. Figure 14 , Figure 15 and Figure 16 The results showed that the Model group significantly upregulated the expression of inflammatory genes IL-1β and TNF-α and downregulated the expression of the antioxidant gene NQO-1. The mRNA expression levels of NQO1, IL-1β, and TNF-α in the testes of mice in the Model+KS-3 group, Model+KS-3 butyrate group, and Model+KS-3 valerate group were significantly different from those in the Model group. Therefore, supplementation with KS-3, KS-3 butyrate, and KS-3 valerate can significantly reduce testicular inflammation and increase antioxidant mRNA expression in STZ-induced oligoasthenospermia mice (P < 0.05).
[0096] 0.05). Figure 17 It can be seen that the Model group caused disordered seminiferous tubule arrangement and spermatocyte atrophy and damage. KS-3-butyrate and KS-3-valerate can effectively alleviate this condition, indicating that KS-3-butyrate and KS-3-valerate can improve testicular pathological damage in oligoasthenospermia mice.
[0097] Test Example 4
[0098] The difference from Experimental Example 1 is that the experimental method is as follows:
[0099] Twenty-five KM mice were randomly divided into four groups: Control group, Model group, KS-3+Model group, KS-3 butyrate+Model group, and KS-3 valerate+Model group, with five mice in each group. Starting from day 0 of the experiment, except for the Control group, all groups were administered sodium valproate (VPA) (500 mg / kg) daily by gavage to establish drug-induced oligoasthenospermia. Except for the Control group, KS-3 (15 mM), KS-3 butyrate (15 mM), and KS-3 valerate (15 mM) were administered by gavage every two days. The Control group received corn oil via gavage as a control. On day 35, tissue samples were collected, and epididymis was used for sperm counting and sperm motility testing.
[0100] See results Figure 18 , Figure 19 and Figure 20 , Figure 18 The results show the weight statistics of the mice in Experiment 4. Figure 19 The results of sperm count statistics in mice in Experiment 4 are as follows. Figure 20 This presents the statistical results of sperm motility in mice from Experiment Example 4. Figures 18-20 It was found that KS-3, KS-3 butyrate, and KS-3 valerate all increased the body weight of mice; the Model group significantly reduced the sperm count and sperm motility of mice, indicating that the oligoasthenospermia mouse model was successfully established; compared with the Model group, the KS-3+Model group, KS-3 butyrate+Model group, and KS-3 valerate+Model group significantly increased the sperm count and sperm motility of oligoasthenospermia mice. Therefore, KS-3, KS-3 butyrate, and KS-3 valerate can improve oligoasthenospermia by increasing sperm count and sperm motility.
[0101] Experimental Example 5
[0102] The difference from Experimental Example 1 is that the experimental method is as follows:
[0103] Fifty KM mice were randomly divided into four groups: Control group, Model group, Model+KS3 valerate group, Model+KS3 hexanoate group, and Model+KS3 heptaate group, with 10 mice in each group. Except for the Control group, each mouse was administered 200 μL of PSNPs (1.5 mg / ml) and 200 μL of DEHP (120 mg / ml) by gavage every two days to induce oligoasthenospermia caused by environmental pollutants. Meanwhile, the Model+KS3 valerate group, Model+KS3 hexanoate group, and Model+KS3 heptaate group were administered KS3 valerate (15 mM), KS3 hexanoate (15 mM), and KS3 heptaate (15 mM) by gavage every two days, respectively. The Control group was treated with corn oil by gavage as a control. On day 35, tissue samples were collected, and the epididymis was used for sperm counting and sperm motility testing.
[0104] See results Figure 21 , Figure 22 and Figure 23 , Figure 21 The results of sperm count statistics in mice in Experiment 5 are as follows. Figure 22 The results show the statistical findings of sperm motility in mice in Experiment 5. Figure 23 This presents the statistical results of forward sperm motility in mice from Experiment Example 5. Figures 21-23 The results showed that the Model group significantly reduced sperm count, sperm motility, and forward sperm motility in mice, indicating successful establishment of the oligoasthenospermia mouse model. Compared to the Model group, KS-3 valerate, KS-3 hexanoate, and KS-3 heptaate significantly increased sperm count, sperm motility, and forward sperm motility in oligoasthenospermia mice. Therefore, KS-3 valerate, KS-3 hexanoate, and KS-3 heptaate can improve oligoasthenospermia by increasing sperm count, sperm motility, and forward sperm motility.
[0105] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. Application of the compound shown in formula (I) in the preparation of drugs that improve male fertility: in, R is selected from H or R1-CO-, wherein R1 is selected from C2 to C10 alkyl groups.
2. The application according to claim 1, characterized in that, The improvement of male fertility includes prevention and treatment of oligospermia and / or protection of testicular tissue.
3. The application according to claim 2, characterized in that, The prevention and treatment of oligospermia and asthenospermia includes increasing sperm count and / or improving sperm motility.
4. The application according to claim 2, characterized in that, The protection of testicular tissue includes one or more of the following: improving tissue morphology, reducing inflammatory factor levels, and upregulating antioxidant factor levels.
5. The application according to claim 4, characterized in that, The inflammatory factors include interleukin-1β and / or tumor necrosis factor; The antioxidant is NAD(P)H quinone dehydrogenase 1.
6. The application according to claim 1, characterized in that, The improvement of male fertility includes improving male fertility impairment caused by pollutants, diseases, or drugs.
7. The application according to claim 6, characterized in that, The pollutants are microplastics and plasticizers; the disease is diabetes; and the drug is sodium valerate.
8. The application according to claim 1, characterized in that, The male is either a human or a mouse.
9. The application according to any one of claims 1 to 8, characterized in that, R1 is selected from C2 to C7 alkyl groups.
10. The application according to claim 9, characterized in that, The R is selected from H, butylcarbonyl, pentylcarbonyl, hexylcarbonyl or heptylcarbonyl.