Study on the Mechanism of Sarsasapogenin in Treating Precocious Puberty by Regulating the HPG Axis

Abstract

The present study aims to investigate the effects and mechanisms of sarsasapogenin resistance to precocious puberty. Female Sprague Dawley rats were divided into a normal (N) group, model (M) group, leuprolide (L) group, and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 micrograms of danazol to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. The development of the uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of the serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) were determined by radioimmunoassay. Also, the expressions of the hypothalamic gonadotropin releasing hormone (GnRH), Kiss-1, G protein-coupled receptor 54 (GPR54), and pituitary gonadotropin releasing hormone receptor (GnRH-R) were detected by RT-PCR. The results showed that compared with the model group, sarsasapogenin could significantly delay the opening time of vaginal, decreased uterine and ovarian coefficients, and reduced uterine wall thickness. Moreover, it can significantly downregulate the levels of serum hormones and reduce the expression of GnRH, GnRH-R, and kiss-1. In summary, our results indicate that sarsasapogenin can regulate the HPG axis through the kiss-1/GPR54 system for therapeutic precocious puberty.

Timosaponin AIII attenuates precocious puberty in mice through downregulating the hypothalamic-pituitary-gonadal axis

“…In rat model of PP, increased KISS1 and GPR54 expression was also observed following danazol treatment. However, GPR54 expression was not affected by sarsasapogenin, another active ingredient from A. asphodeloides, although it has anti-PP activity (Hu et al, 2020b). Apparently, the molecular mechanism of action of sarsasapogenin is different from the mechanism of action of TAIII, which downregulated KISS1 and GPR54 expression elevated by leptin treatment, suggesting that TAIII may exert anti-PP activity through the KISS1/GPR54 system.…”

“…For example, Zhibaidihuang decoction made with A. asphodeloides, Rehmannia glutinosa, Cornus officinalis, peony bark, yam, Poria cocos and Alisma orientalis was found to alleviate PP by reducing the levels of serum hormone FSH, LH and E 2 (Xu & Qiu, 2007;Yu et al, 2014). Sarsasapogenin, a steroidal sapogenin, is a main active ingredient in Zhimu (Bao et al, 2007) and was found to have anti-PP activity through inhibiting the HPGA (Hu et al, 2020a). In addition, pharmacological studies have shown that sarsasapogenin also has activities against thrombosis, Alzheimer's disease, tumor, inflammation, and depression (Han et al, 2018;Wang et al, 2014).…”

Aspartame Intake Delayed Puberty Onset in Female Offspring Rats and Girls

“…After PND 22, the vaginal opening was examined daily at 9:00, and vaginal smears were used to confirm whether the female offspring rats were entering a regular estrous cycle. [21] Vaginal cells were collected through saline lavage and observed under a microscope (Olympus CX23RTFS2, Japan).…”

“…The coefficient of each organ was calculated as follows: ([organ wet weight (g)/body weight (g)] × 10 −4 ). [21]…”

Chemistry, Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design, Development and Therapy

“…Therefore, the role of alternative therapies is important. Hu et al [ 27 ] investigated the effects of sarsasapogenin in treating precocious puberty by regulating the hypothalamus–pituitary–gonadal (HPG) axis. To establish the precocious puberty phase, 5 day old rats were given a single subcutaneous injection of danazol (300 µg).…”