Application of agaro-polysaccharide degradation product in preparation of medicine for improving male reproductive power

Abstract

The invention discloses an application of an agaro-polysaccharide degradation product in preparation of a medicine for improving male reproductive power. According to the method disclosed by the invention, a compound capable of improving sperm motility and male reproductive power is obtained, and a new thought and clue are provided for deeply researching the pathogenesis of oligoasthenospermia and researchers of male reproductive health in the future.

Description

Technical field:

[0001] The invention relates to application of agar polysaccharide degradation products in preparing drugs for improving male fertility, belonging to the fields of reproductive biology technology and biomedicine. Background technology:

[0002] According to the latest report from the World Health Organization, about 17.5% (about one-sixth) of the adult population in the world is currently affected by infertility. Many studies have shown that there are many factors that cause infertility, of which male factors account for about 50%. With the changes in the social environment and the increase in social pressure, the fertility of boys has declined, and the incidence of infertility has gradually increased. Among them, the decline in sperm quality is one of the key issues in the field of reproductive medicine today. A study from the Hebrew University of Israel in 2022 showed that the average sperm count and concentration of men worldwide has dropped by 62% in the past 45 years. Not only that, the team also pointed out that the decline in the average sperm count of men worldwide will continue to accelerate in the 21st century. Faced with such a severe situation, researchers must take action as soon as possible to protect male fertility and prevent further damage to male reproductive health.

[0003] Spermatogenesis is a complex and highly coordinated process in the male reproductive system. This process occurs in the seminiferous tubules of the testicles throughout the entire reproductive cycle. It includes the differentiation of spermatogonia, the initiation of meiosis, the initiation of spermatid elongation, and the release of sperm into the vas deferens. Spermatogenesis is a key component affecting male fertility, and its normal progress is the guarantee of male fertility. Any abnormality in the process of spermatogenesis may lead to male infertility. Therefore, maintaining sperm health is crucial to protecting male fertility.

[0004] Red algae is a kind of algae that mainly lives in the ocean. It has high nutritional value and multiple health benefits and plays an important role in the ecosystem. Agar polysaccharide is a polysaccharide extracted from the cell wall of red algae, mainly composed of agarose and agar gum. Because of its unique gel properties, it has been widely used in the food industry and biomedicine. Agar oligosaccharide is the hydrolysis product of agar polysaccharide. Compared with agar polysaccharide, agar oligosaccharide has better water solubility and biological activity. It has shown great potential in anti-cancer, anti-inflammatory and immune enhancement. In addition, agar oligosaccharide, as a new type of prebiotic, can selectively promote the growth of two beneficial bacteria, bifidobacteria and lactobacilli, in the host intestine, thereby promoting host health. This property helps to improve the overall health of the body and can also have a positive supporting effect on male reproductive health. At the same time, many studies have shown that agar oligosaccharide has antioxidant activity, can scavenge free radicals, and increase the activity of antioxidant enzymes. Oxidative stress is closely related to the decline of male fertility, so the antioxidant activity of agar oligosaccharide helps maintain the health of sperm. Summary of the invention:

[0005] The purpose of the present invention is to provide an effective treatment method for poor male sperm quality and low fertility, that is, the use of agar polysaccharide degradation products in the preparation of drugs, foods or health products for improving male fertility.

[0006] In the present invention, a male mouse disease model of oligoasthenozoospermia was established by intraperitoneal injection of busulfan, and it was found that the sperm motility and semen density of male mice could be significantly improved after adding agar oligosaccharide, a degradation product of agar polysaccharide.

[0007] Therefore, the present invention provides the use of agar polysaccharide degradation products in the preparation of medicines, foods or health products for improving male fertility.

[0008] Preferably, the agar polysaccharide degradation product is agar oligosaccharide.

[0009] Preferably, the medicine, food or health product for improving male fertility is a medicine, food or health product for improving sperm motility and semen density.

[0010] Preferably, the medicine, food or health product contains a therapeutically effective amount of agar polysaccharide degradation product and an acceptable carrier.

[0011] The invention also provides a medicine, food or health product for improving male fertility, which contains an effective amount of agar polysaccharide degradation product.

[0012] The method of the present invention obtains a compound that can be used to improve sperm motility and male fertility, providing new ideas and clues for future in-depth studies on the pathogenesis of oligoasthenozoospermia and for researchers of male reproductive health. Description of the drawings:

[0013] Figure 1 Conceptual image of the research conducted for this invention.

[0014] Figure 2 The results of sperm motility test of three groups of mouse samples.

[0015] Figure 3 The semen density statistics of three groups of mouse samples are shown in Figure 2. Specific implementation method:

[0016] The method of the present invention will be further described below with reference to the accompanying drawings and through specific embodiments.

[0017] Embodiment 1,

[0018] 1. Experimental animal treatment and reagent preparation

[0019] The present invention uses 3-week-old ICR male mice as experimental subjects. The mice are caged in a clean animal room and raised strictly according to standard mouse breeding conditions. The mice are placed in a 12-hour light and 12-hour dark cycle, the room temperature is 23±1°C, the ambient humidity is 50%, and they can drink water and eat freely. All procedures comply with animal ethics standards and experimental specifications. A normal control group (Con), a busulfan-treated group (Bus), and an agar oligosaccharide (purchased from Qingdao Bozhihuili Biotechnology Co., Ltd., product batch number: 2023010401QBF) rescue group (Bus+Ao) were set up. Specific treatment method for mice: This experiment used 3-week-old ICR male mice. The Con group received a single intraperitoneal injection of normal saline at a dose of 7.5 μL per gram of body weight on the morning of the first day, and then continued to receive a single intragastric gavage of normal saline at a dose of 7.5 μL per gram of body weight every morning on the second day for five weeks; the Bus group received a single intraperitoneal injection of 1 mg / mL busulfan according to body weight on the morning of the first day, and then continued to receive a single intragastric gavage of normal saline at a dose of 7.5 μL per gram of body weight every morning on the second day for five weeks; the Bus+Ao group received a single intraperitoneal injection of 1 mg / mL busulfan according to body weight on the morning of the first day, and then continued to receive a single intragastric gavage of 40 mg / mL agar oligosaccharide according to body weight every morning on the second day for five weeks.

[0020] Preparation of busulfan solution: Dissolve 0.1 g busulfan (B2635, Sigma, USA) in 10 mL DMSO solution, dispense 10 mg / mL busulfan solution into 1.5 mL Eppendorf centrifuge tubes and store at 4°C in dark for later use, dilute 10 times with sterile saline before use (final concentration is 1 mg / mL). Use a 1 mL syringe for intraperitoneal injection to ensure that the mouse takes in 30 mg busulfan per kg body weight at one time.

[0021] Preparation of agar oligosaccharide solution: Dissolve agar oligosaccharide powder in sterile saline at a concentration of 40 mg / mL. Perform intragastric administration every morning for 5 weeks. Use a 1 mL syringe to ensure that the daily intake of agar oligosaccharide in mice is 300 mg per kg of body weight.

[0022] 2. Sample collection

[0023] After 5 weeks of continuous gavage treatment, testicles and semen samples from different treatment groups were collected for comparative testing. After the mice were killed by cervical dislocation, alcohol was sprayed on the abdominal skin of the mice and the epididymis was exposed with sterilized surgical scissors. The epididymis of the mice was picked up, sperm was released for in vitro capacitation, and sperm motility data was measured.

[0024] 3. Sperm motility and semen density testing

[0025] Prepare sperm capacitation solution in advance, take α-MEM / F12 and FBS in a volume ratio of 9:1 and mix them evenly, and place them on a 37°C hot plate for preheating. Kill the mice by cervical dislocation, carefully remove the epididymal tail tissue and place it in a 3 cm dish containing 200 μL sperm capacitation solution, cut the epididymal tail with a blade to release fresh sperm and time it for 5 minutes, then draw 20 μL of turbid liquid and dilute it in a new 200 μL sperm capacitation solution and mix it evenly to obtain sperm liquid, and finally draw 4 μL of sperm liquid and drop it on the sperm slide to make the sperm quickly diffuse into the slide, and use SCA sperm quality analyzer to take pictures for sperm motility detection and semen density analysis.

[0026] 4. Results

[0027] Figure 1 This is a conceptual diagram of the research conducted in the present invention. We used busulfan (1 mg / mL) to intraperitoneally inject three-week-old male mice to obtain a mouse model of oligoasthenozoospermia. Starting from the second day after the successful establishment of the model, we performed a single oral gavage of agar oligosaccharide (40 mg / mL) every morning for five weeks. Finally, we evaluated whether oral gavage supplementation of agar oligosaccharide for 5 weeks after busulfan injection could improve sperm motility and semen density. Figure 2 The results of sperm motility test of three groups of mice showed that compared with the control group, the injection of busulfan (1 mg / mL) caused a significant decrease in sperm motility (P<0.05), but after oral administration of agar oligosaccharide (40 mg / mL) for 5 weeks, the sperm motility of mice was significantly improved compared with the busulfan group (P<0.05). Figure 3 The results show that compared with the control group, busulfan injection caused a significant decrease in semen density (P<0.05), but after 5 weeks of intragastric administration of agar oligosaccharide, the semen density of mice was significantly higher than that of the busulfan group (P<0.05).

[0028] The method of the present invention obtains a compound that can be used to improve sperm motility and male fertility, providing new ideas and clues for future in-depth studies on the pathogenesis of oligoasthenozoospermia and for researchers of male reproductive health.

Claims

1. Application of agar polysaccharide degradation products in the preparation of drugs, foods or health products for improving male fertility.

2. The use according to claim 1, characterized in that: The agar polysaccharide degradation product is agar oligosaccharide.

3. The use according to claim 1 or 2, characterized in that: The medicine, food or health product for improving male fertility is a medicine, food or health product for improving sperm motility and semen density.

4. The use according to claim 1, characterized in that: The medicine, food or health product contains an effective amount of agar polysaccharide degradation product and an acceptable carrier.

5. A drug, food or health product for improving male fertility, characterized in that: Contains an effective amount of agar polysaccharide degradation products.

6. The drug, food or health product for improving male fertility according to claim 5, characterized in that: The agar polysaccharide degradation product is agar oligosaccharide.

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