Unkeito promotes follicle development by restoring reduced follicle-stimulating hormone responsiveness in rats with polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is a common disorder resulting in irregular menstruation and infertility due to improper follicular development and ovulation. PCOS pathogenesis is mediated by downregulated follicle-stimulating hormone receptor (FSHR) expression in granulosa cells (GCs); however, the underlying mechanism remains elusive. Unkeito (UKT) is a traditional Japanese medicine used to treat irregular menstruation in patients with PCOS. In this study, we aimed to confirm the effectiveness of UKT in PCOS by focusing on follicle-stimulating hormone (FSH) responsiveness. Methods: A rat model of PCOS was generated by prenatal treatment with 5α-dihydrotestosterone. Female offspring (3-week-old) rats were fed a UKT mixed diet or a normal diet daily. To compare the PCOS phenotype in rats, the estrous cycle, hormone profiles, and ovarian morphology were evaluated. To further examine the role of FSH, molecular, genetic, and immunohistological analyses were performed using ovarian tissues and primary cultured GCs from normal and PCOS model rats. Results: UKT increased the number of antral and preovulatory follicles and restored the irregular estrous cycle in PCOS rats. The gene expression levels of FSHR and bone morphogenetic protein (BMP)-2 and BMP-6 were significantly decreased in the ovarian GCs of PCOS rats compared to those in normal rats. UKT treatment increased FSHR staining in the small antral follicles and upregulated Fshr and Bmps expression in the ovary and GCs of PCOS rats. There was no change in serum gonadotropin levels. In primary cultured GCs stimulated by FSH, UKT enhanced estradiol production, accompanied by increased intracellular cyclic adenosine monophosphate levels, and upregulated the expression of genes encoding the enzymes involved in local estradiol synthesis, namely Cyp19a1 and Hsd17b. Furthermore, UKT elevated the expression of Star and Cyp11a1, involved in progesterone production in cultured GCs in the presence of FSH. Conclusions: UKT stimulates ovarian follicle development by potentiating FSH responsiveness by upregulating BMP-2 and BMP-6 expression, resulting in the recovery of estrous cycle abnormalities in PCOS rats. Restoring the FSHR dysfunction in the small antral follicles may alleviate the PCOS phenotype.

Prescription Research and Clinical Application of Wenjingtang / 中国实验方剂学杂志

The prescription research and clinical application of Wenjingtang were summarized in order to provide reference for the formulation of material standard and the development of compound preparation. By systematically sorting out the relevant ancient medical books and modern literature reports， combined with the relevant policy requirements of the development of compound preparations of famous classical formulas， this paper expounded the existing problems and put forward some suggestions. Wenjingtang is composed of nine herbs， which is derived from Complete Effective Prescriptions for Women's Diseases written by CHEN Zi-ming in Song dynasty. The original medicinal plants and medicinal parts of the formula were basically the same as those recorded in the 2020 edition of Chinese Pharmacopoeia， for example， Paeonia lactiflora was the choice of Paeoniae Radix Alba， Cinnamomi Cortex was selected as Guixin， the rhizoma of Curcuma phaeocaulis was selected as Curcumae Rhizoma. It was suggested that raw products should be selected for decoction pieces and processed according to the methods recorded in the 2020 edition of Chinese Pharmacopoeia. According to the dosage of 1 Liang=40 g， the dosages of Angelicae Sinensis Radix， Chuanxiong Rhizoma， Paeoniae Radix Alba， Cinnamomi Cortex， Moutan Cortex and Curcumae Rhizoma were 20 g， the dosages of Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma and Achyranthis Bidentatae Radix were 40 g， the total amount of this formula was 240 g. The 9 kinds of decoction pieces were crushed （particle size<6 mm） separately and mixed， each dose was 20 g， 525 mL of water was added， and then decocted to 280 mL. After filtration， warm medicine was taken for once a day. According to ancient books， Wenjingtang has the functions of activating blood circulation， regulating menstruation，warming meridians and dispersing cold. It is mainly used to treat dysmenorrhea， irregular menstruation and other diseases in modern clinical practice. In addition， it has certain curative effect on endometriosis， pelvic inflammatory disease， acne， eczema and other skin diseases. Through the research， the historical evolution and clinical application of Wenjingtang are fully clarified， which can provide research for the later development and application of this famous classical formula.