Ovarian cysts disappear after 14-day oral regimen of Korean red ginseng extract in letrozole-induced polycystic ovarian syndrome

Abstract

Objective: Hormonal and inflammatory mechanisms are involved in the pathogenesis of polycystic ovarian syndrome (PCOS), which is a prevalent metabolic disorder among women of reproductive age. We aimed to evaluate the comparative efficiency of short-term oral administration of Korean red ginseng extract (KRGE) and the standard treatment on PCOS by focusing on the histopathological parameters and serum levels of luteinizing hormone (LH), folliclestimulating hormone (FSH), testosterone, and nuclear factor kappa B (NF-κB).

Methods: A PCOS rat model was established by oral gavage of letrozole (1 mg/kg) for 21 days. The serum levels of LH, FSH, testosterone, and NF-κB were measured, and the morphological features and differences of the ovaries were examined in each group using a light microscope before and after 14 days of treatment with oral regimens-KRGE, oral contraceptives (OCPs), KRGE+OCPs, and carboxymethyl cellulose (CMC).

Results: OCPs alone could not normalize the mean ovarian weights of PCOS rats despite the 14-day oral regimen, but they were more effective in reducing the number and size of cysts compared to others. KRGE alone and in combination with OCPs was effective in normalizing abnormal ovarian weights, decreasing LH serum levels, and dissipating the ovarian cysts in PCOS rats. However, when combined with the standard regimen, KRGE showed additional therapeutic effects by efficiently reducing serum testosterone and NF-κB levels.

Conclusion: Our necropsy and histopathological evidence suggests the efficacy of KRGE as a novel integrative medicine against abnormal multiple follicular cysts. However, antiandrogenic and anti-inflammatory effects were only seen in animals that were administered a combination of KRGE and the standard regimen.

Keywords: Luteinizing hormone; NF-kappa B; Ovarian cysts; Panax; Polycystic ovary syndrome.

Fig. 1

Experimental model of the study. PCOS, polycystic ovarian syndrome; CMC, carboxymethyl cellulose.

Fig. 2

Serum levels of luteinizing hormone (LH) (A), follicle-stimulating hormone (FSH) (B), testosterone (C) and nuclear factor kappa B (NF-κB), (D) before and after 14 days of administration of standard regimen (ethinyl estradiol [E]+levonorgestrol [L]), Korean red ginseng extract (KRGE) monotherapy, and their combinational therapy. (A) shows significant difference in LH levels in treatment groups compared to the levels in control group (carboxymethyl cellulose [CMC]), (B) shows significant difference in FSH levels in other groups compared to letrozole group (letrozole [LET]), (C) shows significant difference in serum testosterone levels in E+L and KRGE+E+L groups compared to LET group. (D) shows significant difference in serum NF-κB levels in E+L and KRGE+E+L groups compared to LET group. Different lower-case letters indicate statistically significant differences between the different groups. ^a)P<0.05, significant difference; ^b)P<0.01, moderately significant difference; ^c)P<0.001, highly significant difference.

Fig. 3

Histopathological effects of different interventions on ovarian follicular cyst (×100). (A) Ovarian tissue of letrozole (LET) group with multiple cystic follicles (×100); (B) Ovarian tissue with prominent follicular cyst (×100); (C) Mild ovarian atrophy in Korean red ginseng extract (KRGE) exposed tissues with few follicles (large arrow) and numerous corpus luteum (small arrow). (D) Ovarian tissue of KRGE+ethinyl estradiol (E)+levonorgestrol (L) combination with single follicular cyst (cystic corpora lutea, arrow) (×100).