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. 2017 Jun 13;22(6):978.
doi: 10.3390/molecules22060978.

Hochu-ekki-to Treatment Improves Reproductive and Immune Modulation in the Stress-Induced Rat Model of Polycystic Ovarian Syndrome

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Free PMC article

Hochu-ekki-to Treatment Improves Reproductive and Immune Modulation in the Stress-Induced Rat Model of Polycystic Ovarian Syndrome

Eunkuk Park et al. Molecules. .
Free PMC article

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.

Keywords: Hochu-ekki-to; immune modulation; polycystic ovarian syndrome.

Conflict of interest statement

The authors have declared that no conflict of interest exist.

Figures

Figure 1
Figure 1
Modulation of steroid hormone receptor in PCOS rat model by administration of Hochu-ekki-to. Mean mRNA expression levels of AR (A); ER-α (B); ER-β (C); NGFR (D); and GR (E) in the ovaries of the diestrous (D) and proestrous (P) control groups, the ACTH injection group (A), the cold-stress group (CS), and the groups treated with Hochu-ekki-to following ACTH injection (T1) and cold stress (T2). We used the β-actin as an internal control for normalization of mRNA expressions. Means labeled with different letters are significantly different from each other (p < 0.05, n = 5 in each groups).
Figure 2
Figure 2
Induction of cytokine expression in PCOS rat model by administration of Hochu-ekki-to. Mean mRNA expression levels of IL-2 (A); IL-4 (B); and IFN-γ (C) in the ovaries of the diestrous (D) and proestrous (P) control groups, the ACTH injection group (A), the cold-stress group (CS), and the groups treated with Hochu-ekki-to following ACTH injection (T1) and cold stress (T2). We used the β-actin as an internal control. Means labeled with different letters are significantly different from each other (p < 0.05, n = 5 in each groups).
Figure 3
Figure 3
Involvement of MAP2K2 and Hsp90 for Hochu-ekki-to signaling in PCOS rat model. Mean protein expression levels of MAP2K2 and Hsp 90 in the normal diestrous group (Normal), ACTH injection group (ACTH), cold-stress group (C.S), Hochu-ekki-to-treated ACTH injection group (T1) and Hochu-ekki-to-treated cold-stress group (T2) (A). Sections of ovaries from normal, ACTH, S.C, T1 and T2 were immunostained for MAP2K2 (B) and Hsp 90 (C). Negative control was stained without primary antibody. Means labeled with different letters are significantly different from each other (p < 0.05, n = 5 in each groups). Scale bar 50 μm.
Figure 4
Figure 4
Measurement of intravascular steroid hormone level in PCOS rat model with/without Hochu-ekki-to treatment. Serum LH (A); FSH (B); corticosterone (C); testosterone (D) and estradiol (E) concentrations measured in the ovaries of rats from the diestrous control (D), proestrous control (P), ACTH injection group (A), cold-stress (CS), Hochu-ekki-to-treated ACTH injection (T1), and Hochu-ekki-to-treated cold-stress (T2) groups. Means labeled with different letters are significantly different from each other (p < 0.05, n = 5 in each groups).

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