Abstract

The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control and treatment groups, the latter of which were subjected to stress induced by exposure to adrenocorticotropic hormone (ACTH) or cold temperatures. After these stress inductions, rats were orally treated with dissolved Hochu-ekki-to once per day for 7 days. Rats subjected to the two different stressors exhibited upregulation of steroid hormone receptors (in ovaries) and reproductive hormones (in blood), and consequent stimulation of abnormal follicle development accompanied by elevation of Hsp 90 expression (in ovaries). Treatment with Hochu-ekki-to for 7 days after stress induction increased immune functions, reduced the stress-induced activation of Hsp 90, and normalized the levels of the tested steroid hormone receptors and reproductive hormones. Our findings suggest that stress stimulations may promote the activation of Hsp 90 via the dysregulation of steroid hormone receptors and reproductive hormones, but that post-stress treatment with Hochu-ekki-to improves reproductive and immune functions in the ovaries of stressed rats.

Highlights

  • Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder, affecting approximately 5–10% of infertile women of reproductive age

  • This study examined the efficacy of Hochu-ekki-to in two different stress-induced rat models of PCOS, namely animals treated with adrenocorticotropic hormone (ACTH) injection and cold stress

  • The ACTH injection and cold-stress groups both showed significant increases in their mRNA expression levels of glucocorticoid receptor (GR), IL-2, IL-4, and IFN-γ and concentrations of corticosterone, compared to the corresponding control groups (Figures 1, 2 and 4), but these effects were rescued by administration of Hochu-ekki-to for 7 days

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Summary

Introduction

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder, affecting approximately 5–10% of infertile women of reproductive age. During PCOS, the ovaries produce excessive amounts of androgens, which can interfere with follicle stimulating hormone (FSH) and trigger the Molecules 2017, 22, 978; doi:10.3390/molecules22060978 www.mdpi.com/journal/molecules. Many studies have associated PCOS with an array of metabolic, neuroendocrine, and adrenal abnormalities, the pathogenesis of the polycystic ovary is still unclear. Hochu-ekki-to has been reported to promote certain biological activities, including the activities of NK cells, mitomycin, and macrophages [5,6]. This herbal formula is being used in research to treat patients who are resistant to conventional forms of antibiotics [7]. Hochu-ekki-to has been reported to help relieve stress, decrease fatigue, and suppress carbon tetrachloride-induced hepatotoxicity [8,9,10]

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