Use of hancinbine in treating polycystic ovary syndrome

Abstract

The application belongs to the field of medicine, and particularly relates to application of new litse base in treatment of polycystic ovary syndrome. For a rat PCOS model caused by dehydroepiandrosterone, the new litse base can improve the serum estradiol (E2) level, reduce the follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels, has a significant treatment effect on PCOS, and provides a new drug selection for subsequent treatment of PCOS.

Description

Technical Field

[0001] This invention belongs to the field of medicine, specifically relating to the application of neo-Ligusticum chuanxiong in the treatment of polycystic ovary syndrome. Background Technology

[0002] Polycystic ovary syndrome (PCOS) is a common and highly heterogeneous reproductive endocrine disorder in women of reproductive age, with a global incidence rate of 5%–10%. Clinical features of PCOS include hyperandrogenemia, ovulation abnormalities, and diverse ovarian changes. It is also accompanied by endocrine and metabolic abnormalities, including insulin resistance, glucose and lipid metabolism disorders, and obesity. In 2021, Professor Wu Qunhong's team at Harbin Medical University published a review article in *Human Reproduction*, systematically summarizing and analyzing the disease burden of PCOS in women of reproductive age worldwide in 2017, covering 194 countries. my country ranked among the countries with the fastest-growing age-standardized incidence of PCOS, and third globally. Approximately 90% of PCOS patients experience infertility, and 80% of women with ovulatory dysfunction-related infertility are caused by PCOS. Therefore, the incidence of PCOS is gradually increasing and has become one of the common causes of infertility in women of reproductive age. Thus, the development of treatments for PCOS has significant clinical implications. Summary of the Invention

[0003] This invention provides the application of neo-Ligusticum chuanxiong alkaloid in the treatment of polycystic ovary syndrome (PCOS), which can restore the estrous cycle in rats, improve hormone levels, and has a significant therapeutic effect on PCOS.

[0004] Application of neo-limonene in the preparation of drugs for the treatment of polycystic ovary syndrome.

[0005] Furthermore, the polycystic ovary syndrome mentioned above is caused by dehydroepiandrosterone (DHEA).

[0006] Furthermore, the application of the aforementioned neo-limonene in the preparation of drugs that increase estradiol (E2) levels.

[0007] Furthermore, the application of the aforementioned neo-limonene in the preparation of drugs that reduce the levels of follicle-stimulating hormone (FSH), gonadotropin (LH), and testosterone.

[0008] Furthermore, in the aforementioned application, the concentration of neo-limonene is 100 mg / kg, and the administration method is oral.

[0009] Furthermore, the neo-limonene is extracted from the *Litsea cubeba* tree.

[0010] Furthermore, the preparation method of the aforementioned neo-Litsea alkaloid includes the following steps:

[0011] (1) Dry and chop the bark of the *Cinnamomum camphora* tree. Concentrate the extract using 95% ethanol as a solvent, then adjust the pH to 2-3 with hydrochloric acid or dilute sulfuric acid. Extract with ethyl acetate to remove lipid-soluble components. Then, adjust the pH to 10-14 with ammonia, extract with ethyl acetate, and concentrate to obtain total alkaloids.

[0012] (2) Total alkaloids were obtained by ODS column chromatography and elution with methanol-water to obtain different fractions;

[0013] (3) The obtained fractions were further separated by Sephadex LH-20 gel column elution with methanol; the fractions confirmed to contain neolidinol were further separated by semi-preparative high-performance liquid chromatography (HPLC) using an Agilent semi-preparative column and a mobile phase of methanol-water = 52:48, yielding the compound neolidinol. The purity was identified as above 98%.

[0014] The beneficial effects of this invention are:

[0015] In a rat PCOS model induced by dehydroepiandrosterone (DHEA), neolidinol can increase serum estradiol (E2) levels while decreasing follicle-stimulating hormone (FSH), gonadotropin (LH), and testosterone (T) levels, significantly improving rat hormone levels and demonstrating a significant therapeutic effect on DHEA-induced rat PCOS, providing a new drug option for subsequent treatment of PCOS. Detailed Implementation

[0016] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0017] I. Preparation of Neo-Litsea alkaloids

[0018] (1) Dry and chop the bark of the *Cinnamomum camphora* tree. Concentrate the extract using 95% ethanol as a solvent, then adjust the pH to 2-3 with hydrochloric acid or dilute sulfuric acid. Extract with ethyl acetate to remove lipid-soluble components. Then, adjust the pH to 10-14 with ammonia, extract with ethyl acetate, and concentrate to obtain total alkaloids.

[0019] (2) Total alkaloids were obtained by ODS column chromatography and elution with methanol-water to obtain different fractions;

[0020] (3) The obtained fractions were further separated by Sephadex LH-20 gel column elution with methanol; the fractions confirmed to contain neolidinol were further separated by semi-preparative high-performance liquid chromatography (HPLC) using an Agilent semi-preparative column and a mobile phase of methanol-water = 52:48, yielding the compound neolidinol. The purity was identified as above 98%.

[0021] II. The therapeutic effect of neo-Limonene on PCOS

[0022] Modeling and Drug Administration: A PCOS model was established using dehydroepiandrosterone (DHEA). The blank control group was given sufficient normal feed and sterile water throughout the process. The model group rats were subcutaneously injected with DHEA 60 mg / kg daily. -1 ·d -1 The solution was dissolved in 0.2 mL of the injectable oil and the rats were fed a high-fat diet throughout the treatment. The blank control group was fed a normal diet daily for 3 consecutive weeks. After successful modeling, both the control and model control groups were administered an equal volume of physiological saline by gavage. Quercetin and neosalicyline were dissolved in water to prepare aqueous solutions, and administered at a concentration of 100 mg / kg quercetin and 100 mg / kg neosalicyline by gavage. Serum estradiol (E2), follicle-stimulating hormone (FSH), gonadotropin (LH), and testosterone (T) levels in rats were detected using an ELISA kit. The results are shown in Table 1.

[0023] Table 1 Comparison of serum hormone levels in rats

[0024]

[0025] a Compared with the model group, P<0.05

[0026] Compared with the model group, the levels of LH, FSH and T in rats treated with neolidinoline were significantly reduced, while the level of E2 was significantly increased. Therefore, the biochemical results show that neolidinoline can improve hormone levels in rats and has a significant therapeutic effect on PCOS caused by dehydroepiandrosterone.

[0027] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. The application of neo-Ligusticum chuanxiong in the preparation of drugs for treating polycystic ovary syndrome (PCOS), wherein PCOS is caused by dehydroepiandrosterone (DHEA), and the neo-Ligusticum chuanxiong increases estradiol levels and decreases follicle-stimulating hormone (FSH), gonadotropin (GnRH) and testosterone levels.

2. The application as described in claim 1, characterized in that, In the aforementioned application, the concentration of neolidinone is 100 mg / kg, and the administration method is oral.

3. The application as described in claim 1, characterized in that, The aforementioned neo-limonene was extracted from the *Litsea cubeba* tree.

4. The application as described in claim 1, characterized in that, The preparation method of the aforementioned neo-Litsea alkaloid includes the following steps: (1) Dry the bark of the *Cynanchum paniculatum* tree, chop it, use 95% ethanol as solvent, concentrate the extract, add hydrochloric acid or dilute sulfuric acid to adjust the pH to 2-3, extract with ethyl acetate to remove fat-soluble components; then, adjust the pH to 10-14 with ammonia water, extract with ethyl acetate, concentrate to obtain total alkaloids. (2) Total alkaloids were obtained by ODS column chromatography and elution with methanol-water to obtain different fractions; (3) The obtained fractions were then separated by Sephadex LH-20 gel column elution with methanol; the fractions that were confirmed to contain neolidin were further separated by semi-preparative high performance liquid chromatography with an Agilent semi-preparative column and a mobile phase of methanol-water = 52:48 to obtain the compound neolidin.

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