Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds

Kyeong Ri Kim,Jonghyup Kim,Sehun Lim,Ki Sung Kang,Chang-Eop Kim,Dahae Lee,Hye Lim Lee,Won-Yung Lee,Tuy An Trinh,Ji Yun Baek

doi:10.3390/plants11010023

Abstract

Anemarrhenae rhizome and Phellodendri cortex have historically been used for the treatment of precocious puberty (PP) in oriental medicine. Our study aimed to evaluate the effect of APE, a mixture of the extracts from these herbs, against danazol-induced PP in female rats. The offspring were injected danazol to establish the PP model, and then treated with APE daily, and observed for vaginal opening. At the end of the study, the levels of gonadotropic hormones, such as estradiol, follicle-stimulating hormone, and luteinizing hormone, were determined by ELISA. Moreover, the mRNA expression of GnRH, netrin-1, and UNC5C in hypothalamic tissues was determined by real-time PCR. Network pharmacological analysis was performed to predict the active compounds of APE and their potential actions. APE treatment delayed vaginal opening in rats with PP. In addition, APE treatment reduced LH levels and suppressed UNC5C expression. Gene set enrichment analysis revealed that the targets of APE were significantly associated with GnRH signaling and ovarian steroidogenesis pathways. In conclusion, APE may be used as a therapeutic remedy to inhibit the activation of the hypothalamic–pituitary–gonadal axis.

Highlights

Precocious puberty is an endocrine disorder characterized by the onset of secondary sexual characteristics before the age of eight years in girls and nine years in boys [1]
We investigated the effect of the extract of Anemarrhenae asphodeloides rhizome and Phellodendri cortex, abbreviated as APE, against central precocious puberty (CPP) in an animal model represented by delayed vaginal opening and reduced release of gonadotropic hormones against danazolinduced precocious puberty in female rats
The results of in vivo study indicated that APE treatment delayed vaginal opening in rats with PP by inhibiting the activation of hypothalamic–pituitary–gonadal axis (HPGA)

Summary

Introduction

Precocious puberty is an endocrine disorder characterized by the onset of secondary sexual characteristics before the age of eight years in girls and nine years in boys [1]. The early activation of the hypothalamic–pituitary–gonadal axis (HPGA) leads to the release of gonadotropins that initiate the development of secondary sexual characteristics and accelerate bone maturation in individuals with CPP [4]. CPP can be distinguished from the other two types of precocious puberty by hormone test and bone age determination [1]. The overall prevalence of CPP during the period 2008–2014 was 410.6 for girls and 10.9 for boys. This epidemiologic study showed that the annual incidence of CPP among Korean children rapidly increased by the year during 2008–2014 in both girls (from 89.4 to 415.3) and boys (from 1.6 to 14.7) [5]

Methods

Results

Conclusion