Medicine for treating polycystic ovarian syndrome and application thereof

Abstract

The invention discloses a medicine for treating polycystic ovarian syndrome and application thereof, which can overcome the defects that in the prior art, western medicine for treating polycystic ovarian syndrome is lack of radical treatment, multi-medicine combined application is realized, and complications exist in operations. According to the medicine for treating the polycystic ovarian syndrome, akebia saponin D is the only active ingredient, and the molecular formula of the akebia saponin D is as follows: # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to a medicine for treating polycystic ovary syndrome, and application of the medicine for treating polycystic ovary syndrome in pharmaceutical manufacturing. Background Art

[0002] Polycystic ovary syndrome (PCOS) is a common gynecological endocrine and metabolic disorder. According to statistics, the incidence of PCOS in women of childbearing age is approximately 20%, and the infertility rate in PCOS patients is as high as 50-74%. Clinical symptoms of PCOS include menstrual irregularities (such as amenorrhea, oligomenorrhea, and dysfunctional uterine bleeding), hirsutism, obesity, acanthosis nigricans, acne, and infertility. The main pathological features of PCOS are insulin resistance, androgen excess, ovulatory dysfunction, and polycystic ovaries. Epidemiological data indicate that the high incidence of PCOS is closely related to changes in dietary structure. Today's society has become more diverse, with a significant increase in the intake of high fat and high cholesterol. Excessive lipid intake promotes the development of insulin resistance in PCOS, while increased high cholesterol intake provides more raw materials for androgen synthesis. The intestines are the primary site for nutrient absorption in the body, and intestinal flora play a crucial role in their absorption function. A high-fat, high-cholesterol diet can disrupt the balance of intestinal flora, increasing the number of harmful bacteria and reducing the number of probiotics. This damages the intestinal barrier, allowing more sugar, fat, and cholesterol to enter the bloodstream, accelerating the progression of PCOS. However, currently, there is a lack of clinical treatments targeting the intestines and intestinal flora to treat PCOS, and this area remains underdeveloped.

[0003] Although research on polycystic ovary syndrome has been going on for a long time, there is still no radical treatment for PCOS, and the main treatments are drugs and surgery. Drug treatment for PCOS is mainly divided into three categories: (1) Anti-androgen drugs, mainly including oral contraceptives Diane-35 and spironolactone; however, the main adverse reaction of Diane-35 is the risk of accelerated thrombosis, while spironolactone takes at least 6 months to be effective, and the treatment cycle is long. In addition, when used in large doses, breast tenderness, headache or polyuria may occur, and it may also cause hypotension and hyperkalemia. (2) Insulin sensitizers, mainly metformin; the most common side effect of long-term metformin use is gastrointestinal reactions, which may cause abdominal distension, nausea, vomiting, etc. In addition, metformin can also increase the risk of ectopic pregnancy and congenital malformations. (3) Ovulation-inducing drugs, mainly including gonadotropins; long-term use of ovulation-inducing drugs and hormone drugs may cause endocrine disorders, causing obesity or bone decalcification in patients. Long-term use of metformin can also increase gastrointestinal reactions, such as nausea and vomiting. More importantly, these drugs only have single therapeutic effects, and PCOS treatment often requires the combined use of two or more drugs. Long-term combination use further increases the risk of drug side effects. Therefore, the search for drugs with fewer adverse reactions and more effective treatments is urgent.

[0004] Traditional Chinese Medicine (TCM) believes that PCOS is associated with kidney, spleen, and liver dysfunction, and treatment often utilizes a combination of kidney-tonifying and liver-soothing, spleen-strengthening and phlegm-resolving therapies. Akebia saponin D (ASD), also known as Dipsacus root saponin VI, is a triterpenoid saponin derived from the dried rhizome of Dipsacus root. The Shennong Bencao Jing (Classic of Materia Medica) lists Dipsacus root as a top-grade medicinal herb. In TCM, Dipsacus root is considered bitter and pungent, slightly warm, and enters the liver and kidney meridians. It has the potential to tonify the liver and kidneys, strengthen tendons and bones, regulate blood circulation, and stop metrorrhagia. Dipsacus root is also commonly found in traditional Chinese medicine formulas for PCOS. Akebia saponin D (ASD) is the primary active ingredient in Dipsacus root extracts. Modern pharmacological studies have shown that ASD has low oral absorption and utilization, but exhibits lipid-lowering, obesity-inhibiting, insulin resistance-modifying, and anti-inflammatory properties. However, no studies or reports have been published on the use of Akebia saponin D in the treatment and / or prevention of PCOS. Summary of the Invention

[0005] To overcome the shortcomings of the prior art, the present invention aims to provide a drug for treating polycystic ovary syndrome that avoids the shortcomings of prior Western medicine and Western drugs in treating polycystic ovary syndrome, such as the lack of a radical cure, the numerous side effects of combined use of multiple drugs, and the complications of surgery. The technical solution of the present invention is that the drug for treating polycystic ovary syndrome contains akebifenosidone D as the sole active ingredient, and the molecular formula of akebifenosidone D is as follows:

[0006]

[0007] Preferably, the akebiasaponin D is prepared together with conventional pharmaceutical excipients into injections, tablets, pills, capsules, lozenges, suspensions, emulsions, or suppositories.

[0008] Preferably, the oral effective dose of the akebiasaponin D is 50-100 mg / kg body weight per day.

[0009] Preferably, the oral effective dose of the akebiasaponin D is 50 mg / kg body weight per day, for 28 days.

[0010] Preferably, Akebia saponin D treats polycystic ovary syndrome by regulating intestinal flora, lowering blood lipid levels, and improving insulin resistance and serum androgen levels. The intestinal flora is Firmicutes, Alternaria, Bacteroides, Prevotella, Lactobacillus, Butyricum, or Bifidobacterium.

[0011] Preferably, the blood lipids refer to serum total cholesterol, triglycerides and free fatty acid levels.

[0012] Preferably, the improvement of insulin resistance refers to reducing fasting insulin levels and insulin resistance index.

[0013] Preferably, the improvement of hormone levels is to reduce the testosterone content in serum and reduce the ratio of luteinizing hormone LH to follicle-stimulating hormone FSH.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] (1) This invention proposes for the first time the use of akebiasaponin D as the sole active ingredient to treat PCOS and explores the therapeutic mechanism of akebiasaponin D in treating PCOS by regulating intestinal flora.

[0016] (2) The experimental results showed that continuous oral administration of Akebia saponin D for 28 days at a dose of 50 mg / kg body weight per day can effectively alleviate the symptoms related to PCOS, such as reduced blood lipid levels, disappearance of insulin resistance, increase in the number of mature follicles, and restoration of normal male hormone levels.

[0017] (3) The present invention provides a new therapeutic drug with low cost, few side effects and significant efficacy. It overcomes the shortcomings of the existing traditional Chinese and Western medicine in the treatment of polycystic ovary syndrome, such as the lack of radical cure, the large side effects of combined drug use, and the complications of surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the PCA analysis diagram of the mouse intestinal flora;

[0019] Figure 2 Heat map for genus-level analysis of mouse intestinal flora;

[0020] Figure 3 HE staining and AB-PAS staining of mouse small intestine tissue;

[0021] Figure 4 It is a bar graph of mouse body weight index;

[0022] Figure 5 is a bar graph of mouse ovary weight;

[0023] Figure 6 HE staining of mouse ovary;

[0024] Figure 7 A bar graph is shown for the fasting blood glucose levels of mice;

[0025] Figure 8 A bar graph is shown for fasting insulin levels in mice;

[0026] Figure 9 is a bar graph of mouse serum alanine aminotransferase (ALT) levels;

[0027] Figure 10 is a bar graph of mouse serum aspartate aminotransferase (AST) levels;

[0028] Figure 11 is a bar graph of mouse serum creatinine (Cr) levels;

[0029] Figure 12 HE staining of mouse liver;

[0030] Figure 13 HE staining of mouse kidney;

[0031] Figure 14 This is a table showing the percentages of each phase of the sexual cycle in the PCOS mouse model;

[0032] Figure 15 This is a statistical table of the ratios of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone in mouse serum;

[0033] Figure 16 This is the statistical table of mouse insulin resistance index;

[0034] Figure 17 This is a table showing the levels of total cholesterol, triglycerides, and free fatty acids in mouse serum. DETAILED DESCRIPTION

[0035] The molecular formula of Akebia saponin D is C 47 H 76 O 18 , the molecular formula of Akebia saponin D is as follows:

[0036]

[0037] The embodiments of the present invention are described in detail below.

[0038] Example 1 Study on the effect of Akebia saponin D on the intestinal barrier and intestinal flora in polycystic ovary syndrome animal models

[0039] Experimental animals: C57BL / 6J female mice, 21 days old.

[0040] Experimental Methods: Mice were numbered and randomly assigned to five groups: control, PCOS, PCOS + ASD (Akebia saponin D) low-dose group (ASD-L - 50 mg / kg), PCOS + ASD high-dose group (ASD-H - 100 mg / kg), and PCOS + metformin (Met - 50 mg / kg), with six mice in each group. Control mice received daily injections of equal volumes of olive oil and saline and a normal diet. PCOS model mice received daily subcutaneous injections of DHEA (6 mg / 100 g dissolved in 0.2 mL olive oil) and a high-fat diet. The insulin resistance index (IRI) was calculated using the formula: fasting blood glucose × fasting insulin / 22.5. Mice with an IRI greater than 2.7 were considered successful PCOS insulin resistance models. ASD-treated mice received daily injections of the same dose of DHEA and oral gavage with Akebia saponin D (50 and 100 mg / kg). The mice in the metformin group were injected with the same dose of DHEA daily and orally gavaged with metformin (50 mg / kg) to establish the model for 28 days.

[0041] Solvent: Akebia saponin D and metformin are prepared with normal saline.

[0042] Detection indicators: Detect and compare the pathological changes in the small intestine and changes in intestinal flora of each group of mice after drug intervention, where the intestinal flora refers to the flora in the intestinal contents.

[0043] Detection methods: 1) HE staining to observe the pathological morphology of the small intestine of mice in each group: The small intestine tissues of mice in each group were fixed in 4% paraformaldehyde solution for 48 hours, and 5 μm thick paraffin-embedded tissue sections were prepared. After dewaxing and hydration, HE (hematoxylin-eosin) staining was performed. The pathological morphology of the small intestine tissue of mice was observed under a microscope and photographed. 2) AB-PAS (Alcian blue-periodic acid-Schiff staining) was used to observe the secretion of mucus granules in the small intestinal epithelium of mice in each group. The small intestine tissues of mice in each group were fixed in 4% paraformaldehyde solution for 48 hours, and 5 μm thick paraffin-embedded tissue sections were prepared. After dewaxing and hydration, AB-PAS staining was performed. The secretion of mucus granules in the small intestinal tissue of mice was observed under a microscope and photographed. 3) Place each numbered mouse in each group in a cage covered with sterile gauze. After the mice defecate naturally, place the feces into sterile RNase-free cryovials on ice. Collect 50-100 mg of feces from each mouse and quickly store the cryovials in liquid nitrogen. After extracting total microbiome DNA, perform 16S rRNA sequencing.

[0044] Test results: Combined Figure 1 It can be seen that the control group and the PCOS model group are far apart, indicating that the bacterial flora composition of the two groups is quite different. The low-dose ASD treatment group and the high-dose ASD treatment group are similar, and the distance between the metformin treatment group and the PCOS group is small, and the distance between the metformin treatment group and the control group is far away. The results suggest that the changes in intestinal flora after low-dose and high-dose ASD treatment may be related to the improvement of PCOS symptoms. Figure 2 The intestinal flora was classified at the genus level, and the results showed that after ASD treatment, the abundance of Firmicutes, Bacteroides, and Prevotella, which are positively correlated with insulin resistance, decreased, while the abundance of probiotics Lactobacillus, Butyricum, and Bifidobacterium, which improve metabolism, increased. Figure 3 The small intestinal tissue of mice in the PCOS group showed shortened and damaged intestinal villi, with epithelial destruction and inflammatory cell infiltration in the mucosal layer. AB-PAS staining of the small intestinal tissue revealed that the secretion of mucus particles by intestinal epithelial cells decreased after a high-fat diet. ASD and Met intervention inhibited intestinal villus damage and increased mucus particle production. These results suggest that the PCOS model combined with a high-fat diet impairs intestinal barrier function and increases intestinal permeability, potentially leading to elevated blood lipid and cholesterol levels and ultimately promoting PCOS disease progression. Both ASD and MET effectively inhibited intestinal villus damage.

[0045] Example 2 The effects of Akebia saponin D on the estrous cycle, ovarian weight and mature follicles in an animal model of polycystic ovary syndrome were studied.

[0046] Experimental animals: C57BL / 6J female mice, 21 days old.

[0047] Experimental Methods: Mice were numbered and randomly assigned to five groups: control, PCOS, PCOS + ASD (Akebia saponin D) low-dose group (ASD-L - 50 mg / kg), PCOS + ASD high-dose group (ASD-H - 100 mg / kg), and PCOS + metformin (Met - 50 mg / kg), with six mice in each group. Control mice received daily injections of equal volumes of olive oil and saline and a normal diet. PCOS model mice received daily subcutaneous injections of DHEA (6 mg / 100 g dissolved in 0.2 mL olive oil) and a high-fat diet. The insulin resistance index (IRI) was calculated using the formula: fasting blood glucose × fasting insulin / 22.5. Mice with an IRI greater than 2.7 were considered successful PCOS insulin resistance models. ASD-treated mice received daily injections of the same dose of DHEA and oral gavage with Akebia saponin D (50 and 100 mg / kg). The mice in the metformin group were injected with the same dose of DHEA daily and orally gavaged with metformin (50 mg / kg) to establish the model for 28 days.

[0048] Solvent: Akebia saponin D and metformin are prepared with normal saline.

[0049] Detection indicators: vaginal smear method was used to determine the estrous cycle of mice, the weight of mice and ovaries were weighed, and H&E staining was used to observe the pathological morphology of ovarian tissue in each group of mice.

[0050] Detection Methods: 1) After 28 days of drug intervention, observe changes in the mouse sexual cycle based on the histological characteristics of vaginal smears at each stage of the mouse sexual cycle. 2) Weigh the mouse ovaries. 3) Fix one ovary from each group of mice in 4% paraformaldehyde solution for 48 hours. Prepare 5 μm thick paraffin-embedded tissue sections. After dewaxing and hydration, perform hematoxylin and eosin staining. Observe the pathological morphology of the mouse ovarian tissue, including the size and shape of the follicles, under a microscope and take photos.

[0051] Test results: Combined Figure 14 It can be seen that compared with the model group without drug intervention, Akebia saponin D has a significant improvement effect on the sexual cycle of the polycystic ovary syndrome mouse model, and its effect is better than the positive control drug metformin. Figure 4 It can be seen that there is no significant difference in body weight between the groups after PCOS modeling, indicating that DHEA preparation of polycystic ovary syndrome animal model has little effect on its body weight, and the effect of short-term drug intervention on the body weight of mice is not significant. After the experiment, the ovaries of the mice were removed and the wet weight of the ovaries was measured using an electronic balance. Figure 5It can be seen that the wet weight of the ovaries of the model group mice increased compared with the normal control group, which was statistically significant. The wet weight of the ovaries of the low-dose and high-dose groups of Akebia saponin D was significantly lower than that of the model group after intervention. Although the wet weight of the ovaries decreased after metformin treatment, there was no statistical difference compared with the PCOS model group. Therefore, it can be concluded that the ovarian volume and wet weight of mice with successful DHEA modeling increased under basically the same body weight. Akebia saponin D can significantly reduce the wet weight of the ovaries, but it was not statistically significant compared with metformin. Figure 6 The ovaries in the normal control group were brightly colored, with multiple corpora lutea and follicles of varying developmental stages visible under the microscope, all intact and neatly arranged. In the PCOS model group, the ovaries were pale, with multiple cystically dilated follicles visible under the microscope. The granulosa cell layer was 1-2 layers or absent, and the corpora lutea were reduced. In the ASD-L and ASD-H groups, ovarian color improved, cystically dilated follicles decreased, and the number of follicles and corpora lutea at varying developmental stages increased. In the metformin group, the ovaries were similar in color to the Akebia saponin D group, with an increase in the number of follicles and corpora lutea.

[0052] Example 3 The effect of Akebia saponin D on sex hormones in an animal model of polycystic ovary syndrome was studied.

[0053] Experimental animals: C57BL / 6J female mice, 21 days old.

[0054] Experimental Methods: Mice were numbered and randomly assigned to five groups: control, PCOS, PCOS + ASD (Akebia saponin D) low-dose group (ASD-L - 50 mg / kg), PCOS + ASD high-dose group (ASD-H - 100 mg / kg), and PCOS + metformin (Met - 50 mg / kg), with six mice in each group. Control mice received daily injections of equal volumes of olive oil and saline and a normal diet. PCOS model mice received daily subcutaneous injections of DHEA (6 mg / 100 g dissolved in 0.2 mL olive oil) and a high-fat diet. The insulin resistance index (IRI) was calculated using the formula: fasting blood glucose × fasting insulin / 22.5. Mice with an IRI greater than 2.7 were considered successful PCOS insulin resistance models. ASD-treated mice received daily injections of the same dose of DHEA and oral gavage with Akebia saponin D (50 and 100 mg / kg). The mice in the metformin group were injected with the same dose of DHEA daily and orally gavaged with metformin (50 mg / kg) to establish the model for 28 days.

[0055] Solvent: Akebia saponin D and metformin are prepared with normal saline.

[0056] Detection indicators: serum testosterone (T) content, estradiol (E2) content, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) content, and LH / FSH ratio.

[0057] Detection method: Use Elisa kit to detect the content of the above four hormones

[0058] Test results: Combined Figure 15 It can be seen that the level of androgen testosterone increased significantly after PCOS modeling, while the content of estradiol decreased. ASD treatment can reduce the level of androgen testosterone after PCOS modeling and increase the serum content of estradiol. The effect of high-dose ASD in reducing androgen levels is better than that of the metformin group.

[0059] Example 4 The effect of Akebia saponin D on insulin resistance in an animal model of polycystic ovary syndrome was studied.

[0060] Experimental animals: C57BL / 6J female mice, 21 days old.

[0061] Experimental Methods: Mice were numbered and randomly assigned to five groups: control, PCOS, PCOS + ASD (Akebia saponin D) low-dose group (ASD-L - 50 mg / kg), PCOS + ASD high-dose group (ASD-H - 100 mg / kg), and PCOS + metformin (Met - 50 mg / kg), with six mice in each group. Control mice received daily injections of equal volumes of olive oil and saline and a normal diet. PCOS model mice received daily subcutaneous injections of DHEA (6 mg / 100 g dissolved in 0.2 mL olive oil) and a high-fat diet. The insulin resistance index (IRI) was calculated using the formula: fasting blood glucose × fasting insulin / 22.5. Mice with an IRI greater than 2.7 were considered successful PCOS insulin resistance models. ASD-treated mice received daily injections of the same dose of DHEA and oral gavage with Akebia saponin D (50 and 100 mg / kg). The mice in the metformin group were injected with the same dose of DHEA daily and orally gavaged with metformin (50 mg / kg) to establish the model for 28 days.

[0062] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0063] Detection indicators: Fasting blood glucose and fasting serum insulin were tested on mice, and the insulin resistance index was calculated.

[0064] Detection methods: 1) Fasting blood glucose levels in mice were measured using a blood glucose meter and test strips. 2) Insulin levels were measured using an Elisa kit.

[0065] Test results: Combined Figure 7 It can be seen that PCOS modeling and Akebia saponin D and metformin treatment had no significant effect on the fasting blood glucose levels of mice. Figure 8Yes, the fasting blood insulin levels in the model group were higher than those in the normal control group; the fasting insulin levels in the ASD treatment group were lower than those in the PCOS group, and the effect of the ASD high-dose group was better than that of the Met group. Figure 16 The statistical results of the insulin resistance index showed that both ASD and Met treatments could improve insulin resistance, and the effect was better in the ASD high-dose group.

[0066] Example 5 The effect of Akebia saponin D on blood lipid levels in polycystic ovary syndrome animal models was studied.

[0067] Experimental animals: C57BL / 6J female mice, 21 days old.

[0068] Experimental Methods: Mice were numbered and randomly assigned to five groups: control, PCOS, PCOS + ASD (Akebia saponin D) low-dose group (ASD-L - 50 mg / kg), PCOS + ASD high-dose group (ASD-H - 100 mg / kg), and PCOS + metformin (Met - 50 mg / kg), with six mice in each group. Control mice received daily injections of equal volumes of olive oil and saline and a normal diet. PCOS model mice received daily subcutaneous injections of DHEA (6 mg / 100 g dissolved in 0.2 mL olive oil) and a high-fat diet. The insulin resistance index (IRI) was calculated using the formula: fasting blood glucose × fasting insulin / 22.5. Mice with an IRI greater than 2.7 were considered successful PCOS insulin resistance models. ASD-treated mice received daily injections of the same dose of DHEA and oral gavage with Akebia saponin D (50 and 100 mg / kg). The mice in the metformin group were injected with the same dose of DHEA daily and orally gavaged with metformin (50 mg / kg) to establish the model for 28 days.

[0069] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0070] Detection indicators: serum total cholesterol (TC), total triglycerides (TG), free fatty acids (NEFA)

[0071] Detection method: Use a chemical kit to detect the content of three substances.

[0072] Test results: After the experiment was completed, the eyeballs were removed and blood was collected into a 1.5ml centrifuge tube. The blood was centrifuged at 3000rpm at room temperature to obtain serum. The kit was used to detect total cholesterol (TC), triglycerides (TG), and free fatty acids (NEFA) in the serum. The results were as follows: Figure 17As shown in the data, there was no significant difference in the changes of serum TG after PCOS modeling, but the TC and NEFA levels were significantly increased. After treatment with Akebia saponin D, the TC and NEFA levels decreased, but no significant difference was found between the Met group and the model group.

[0073] Example 6 The effects of Akebia saponin D on the liver and kidney functions of an animal model of polycystic ovary syndrome were studied.

[0074] Experimental animals: C57BL / 6J female mice, 21 days old.

[0075] Experimental Methods: Mice were numbered and randomly assigned to five groups: control, PCOS, PCOS + ASD (Akebia saponin D) low-dose group (ASD-L - 50 mg / kg), PCOS + ASD high-dose group (ASD-H - 100 mg / kg), and PCOS + metformin (Met - 50 mg / kg), with six mice in each group. Control mice received daily injections of equal volumes of olive oil and saline and a normal diet. PCOS model mice received daily subcutaneous injections of DHEA (6 mg / 100 g dissolved in 0.2 mL olive oil) and a high-fat diet. The insulin resistance index (IRI) was calculated using the formula: fasting blood glucose × fasting insulin / 22.5. Mice with an IRI greater than 2.7 were considered successful PCOS insulin resistance models. ASD-treated mice received daily injections of the same dose of DHEA and oral gavage with Akebia saponin D (50 and 100 mg / kg). The mice in the metformin group were injected with the same dose of DHEA daily and orally gavaged with metformin (50 mg / kg) to establish the model for 28 days.

[0076] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0077] Detection indicators: aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood creatinine (Cr), liver HE staining, kidney HE staining.

[0078] Detection method: ALT, AST, and Cr levels were detected using chemical kits, and liver and kidney lesions were observed using HE staining.

[0079] Test results: The results are as follows Figures 9-11 As shown, ELISA kits were used to detect serum ALT, AST, and creatinine levels. After PCOS modeling and oral administration of Akebia saponin D and metformin, there was no statistical difference in liver and kidney function between the groups, indicating that the low-dose and high-dose ASD groups did not show significant liver and kidney toxicity. Figure 12As shown in the figure, the livers of the normal group, ASD-L group, and ASD-H group showed intact lobular structures, clear sinusoids, radially arranged hepatocytes, uniform size, single nuclei, and normal nuclear-cytoplasm ratio. In the model group and metformin group, some hepatocytes showed fatty degeneration, increased cytoplasm transparency, and unclear cytoplasm. Liver pathology showed that the Akebia saponin D treatment group had a protective effect on the hepatic fatty lesions caused by the high-fat diet in the early stage of PCOS model, which may be related to the improvement of insulin resistance. Figure 13 As shown, the kidneys in all groups were normal, with intact renal pelvic epithelial cells and no lesions in the glomeruli and renal tubules.

[0080] Serum insulin ELISA results from each group of mice indicate that both serum insulin levels and the insulin resistance index (IRI) in the model group were higher than those in the normal control group, with the IRI exceeding 2.7, similar to serum insulin levels in insulin-resistant patients with polycystic ovary syndrome (PCOS), indicating successful modeling. Treatment with Akebia saponin D significantly altered the intestinal microbiota of mice. Combined with previous reports, this study found that Akebia saponin D treatment significantly increased the content of probiotics in the intestine. Therefore, it is speculated that the therapeutic effects of ASD may be related to the intestinal microbiota. Furthermore, the high-dose ASD treatment group significantly reduced fasting serum insulin levels and had a significant reversal effect on the IRI, with no statistically significant difference compared to the Western medication metformin. Regarding sex hormone regulation, ASD treatment significantly reduced androgen levels, lower than those in the metformin group, and significantly decreased the LH / FSH ratio.

[0081] The above experimental results show that Akebia saponin D can improve the serum insulin content and insulin resistance index in mice with polycystic ovary syndrome and insulin resistance, thereby reversing their disrupted sexual cycles and showing a significant therapeutic effect on polycystic ovary syndrome. Furthermore, Akebia saponin D is safe and has no hepatotoxicity or renal toxicity. Therefore, it can be concluded that Akebia saponin D can be used to prepare drugs for the treatment of polycystic ovary syndrome and has good prospects.

[0082] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention are still within the scope of protection of the technical solution of the present invention.

Claims

1. A drug for treating polycystic ovary syndrome, characterized by: Akebiasaponin D is the only active ingredient. The molecular formula of Akebiasaponin D is as follows:

2. Use of the drug for treating polycystic ovary syndrome according to claim 1 in pharmaceutical manufacturing, characterized in that: The akebia saponin D is prepared together with conventional pharmaceutical excipients into injections, tablets, pills, capsules, lozenges, suspensions, emulsions, or suppositories.

3. Use of the drug for treating polycystic ovary syndrome according to claim 1 in pharmaceutical preparation, characterized in that: The oral effective dose of the akebiasaponin D is 50-100 mg / kg body weight per day.

4. Use of the drug for treating polycystic ovary syndrome according to claim 1 in pharmaceutical preparation, characterized in that: The oral effective dose of the akebiasaponin D is 50 mg / kg body weight per day, taken orally for 28 days.

5. Use of the drug for treating polycystic ovary syndrome according to claim 1 in pharmaceutical preparation, characterized in that: The akebia saponin D regulates intestinal flora, lowers blood lipid levels, and improves insulin resistance and hormone levels to treat polycystic ovary syndrome.

6. Use of the drug for treating polycystic ovary syndrome according to claim 5 in pharmaceutical preparation, characterized in that: The intestinal flora is Firmicutes, Alternaria, Bacteroides, Prevotella, Lactobacillus, Butyricum, or Bifidobacterium.

7. Use of the drug for treating polycystic ovary syndrome according to claim 5 in pharmaceutical preparation, characterized in that: The blood lipids refer to the contents of serum total cholesterol, triglycerides and free fatty acids.

8. Use of the drug for treating polycystic ovary syndrome according to claim 5 in pharmaceutical preparation, characterized in that: The improvement of insulin resistance refers to reducing fasting insulin levels and insulin resistance index.

9. Use of the drug for treating polycystic ovary syndrome according to claim 5 in pharmaceutical manufacturing, characterized in that: The improvement of hormone levels is to reduce the testosterone content in serum and reduce the ratio of luteinizing hormone LH to follicle-stimulating hormone FSH.

Images