peoniflorin and Polycystic-Ovary-Syndrome

Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder characterized by androgen excess and ovulatory dysfunction; it is now known to be closely linked to metabolic syndrome. Recent research suggests that insulin resistance plays an important role in the pathogenesis of PCOS which may lead to the excessive production of androgens by ovarian theca cells. Currently there is no single drug that can treat both the reproductive and metabolic complications of the disorder. Existing pharmaceutical agents such as hormonal therapies have been associated with side effects and are not appropriate for PCOS women with infertility. Additionally, insulin sensitizing agents useful for treating the metabolic abnormalities in PCOS have limited efficacy for treating reproductive aspects of the disorder. Chinese herbal medicines have a long history of treating gynaecological problems and infertility and therefore may be a novel approach to the treatment of PCOS. Current research demonstrates that the compounds isolated from herbs have shown beneficial effects for PCOS and when combined in an herbal formula can target both reproductive and metabolic defects simultaneously. Therefore, further investigation into Chinese herbal medicine in the treatment of PCOS is warranted.

Topics: Androgens; Berberine; Drugs, Chinese Herbal; Female; Ginsenosides; Glucosides; Humans; Insulin Resistance; Monoterpenes; Phenanthrenes; Phytotherapy; Polycystic Ovary Syndrome; Resveratrol; Stilbenes; Theca Cells

Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrine disorders which are involved in complicated and unknown pathogenic mechanisms. Paeoniflorin (PAE) plays a significant anti-fibrotic role according to previous studies. The aim of the present study was to investigate the effect of PAE on ovarian fibrosis and its underlying mechanism in PCOS development. An animal model of PCOS was established by subcutaneous injection of 60mg/kg/d dehydroepiandrosterone (DHEA) for 35 consecutive days. Rats in PAE-L, PAE-M and PAE-H groups were administrated by gavage with PAE (20, 40, 80 mg/kg/d) for 4 weeks. Our results indicated that DHEA-induced PCOS rats showed similar phenotypes with PCOS patients. PAE could significantly block the DHEA-induced decline of ovary weight and organ coefficient, shorten the prolonged diestrus period, and regulate the irregular estrous cycle of PCOS rats. Moreover, PAE regulated reproductive hormone levels and improved ovarian fibrosis induced by DHEA. PAE treatment could also reduce the expression levels of TGF-β1 and Smad3, and increase the expression levels of Smad7 and MMP2. In conclusion, PAE significantly attenuated the ovarian fibrosis in PCOS, which could be mediated by TGF-β1/Smads signaling pathway. Herein, PAE can be used for the treatment of ovarian fibrosis in PCOS progression.

Topics: Animals; Dehydroepiandrosterone; Disease Models, Animal; Estrous Cycle; Female; Glucosides; Monoterpenes; Ovary; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

Polycystic Ovarian Syndrome (PCOS) is a complex endocrine and reproductive disorder. A main hallmark includes increased androgen production. The root of Paeonia lactiflora Pall. (Bai Shao) is used in Chinese herbal medicine for reproductive disorders, however its effects and mechanisms on ovarian theca cells has not yet been fully elucidated.. The aim of this study was to evaluate effect of paeoniflorin extract (PFE), the main constituents of Bai Shao, on androgen production in ovarian theca cells.. Primary murine theca cells were treated with concentrations of PFE (1-100 µg/mL) in the presence of dexamethasone (10 µM) with media-only treated cells used as the control. After 24 h, culture media was collected for biochemistry assays of testosterone and progesterone. Expression of key steroidogenic enzymes, cholesterol side-chain cleavage (CYP11A1) and 17α-hydroxylase (CYP17A1) was characterized using immunofluorescence staining, immunoblotting and qRT-PCR.. Dexamethasone significantly enhanced testosterone secretion (P < 0.05 vs. the control cells). PFE reversed over-production of testosterone induced by dexamethasone in a dose-dependent manner. The treatment with PFE also normalized production of progesterone in dexamethasone-treated cells. Expression of CYP11A1 and CYP17A1 in the theca cells were visualised by immunofluorescence staining. All doses of PFE significantly inhibited CYP17A1 expression detected by immunoblotting, but only 100 µg/mL of PFE downregulated CYP11A1 expression and reduced CYP11A1 significantly in dexamethasone-treated theca cells.. PFE may reduce over-secretion of testosterone in theca cells through downregulation of CYP17A1 and CYP11A1. These findings provide scientific evidence to treat ovarian hyperandrogenism with the root of Paeonia lactiflora Pall.

Topics: Animals; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme; Dexamethasone; Down-Regulation; Female; Glucosides; Mice; Monoterpenes; Polycystic Ovary Syndrome; Steroid 17-alpha-Hydroxylase; Testosterone; Theca Cells

Topics: Administration, Oral; Animals; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Female; Flavanones; Glucosides; Glycyrrhetinic Acid; Glycyrrhizic Acid; Monoterpenes; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry