The effects and mechanisms of paeoniflorin on murine ovarian cells for the treatment of polycystic ovarian syndrome
- Publication Type:
- Thesis
- Issue Date:
- 2018
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Polycystic Ovarian Syndrome (PCOS) is a complex disorder associated with various reproductive, metabolic and cardiovascular abnormalities and is present in approximately 15% of women of reproductive age. The hallmarks include androgen excess, ovulatory dysfunction and insulin resistance which is believed to play a role in the pathogenesis of the disorder. Although the exact mechanisms of PCOS are unknown, intrinsic dysfunction of ovarian theca and granulosa cells are also thought to contribute to altered steroid production and follicle development which may explain the clinical features of the syndrome.
Metformin, an insulin sensitising agent may improve both metabolic and reproductive aspects of the disorder, however, the development of new therapeutic agents for PCOS is still required. Women with PCOS are inclined to seek complementary and alternative treatment options such as Chinese Herbal Medicine, warranting further investigation into the efficacy of the herbs commonly used. Paeoniflorin, the major compound of the herb, Radix Paeoniae Albus has demonstrated the ability to ameliorate insulin resistance in animal models, however the effects and mechanisms of paeoniflorin for the treatment of PCOS has yet to be elucidated.
This study therefore used a dexamethasone-induced in vitro model of PCOS in murine theca and granulosa cells to determine the effects of paeoniflorin on secretion of key hormones testosterone, progesterone and oestradiol, cell proliferation as well as the molecular mechanisms in which paeoniflorin may regulate steroid production. Dexamethasone (10 µM) increased theca cell androgen production and adversely affected oestradiol: progesterone ratios in granulosa cells. Meanwhile, paeoniflorin (100 µg/mL) decreased androgen production in dexamethasone-induced theca cells and maintained normal oestradiol: progesterone ratios in granulosa cells. In theca cells, this was shown to be through downregulation of cholesterol side-chain cleavage enzyme and 17,20-lyase protein expression. Paeoniflorin also increased mRNA gene expression of CYP11A1 which may indicate influence over transcription factors or post-translation modifiers, particularly in relation to cell differentiation.
Together, these results suggest that firstly, dexamethasone can be considered a useful in vitro model of PCOS in murine ovarian cells. Secondly, paeoniflorin may be a novel agent for the treatment of PCOS by ameliorating hyperandrogenism and improving ovarian function. Further research into the effect of paeoniflorin in differentiation of theca cells as well as the molecular mechanisms in which paeoniflorin attenuates hormones in granulosa cells is needed. Finally, this research can potentially support future animal or clinical studies to further improve the treatment options and quality of life for women with PCOS.
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