Beneficial effects of Heqi san on rat model of polycystic ovary syndrome through the PI3K/AKT pathway

Abstract

BackgroundHeqi San, a traditional Chinese medicine (TCM) has been reported to regulate hormone levels in patients with metabolic disease, suggesting a potential clinical application. In the current study, we aimed to elucidate the effect of Heqi San on rat model of polycystic ovary syndrome (PCOS).MethodPCOS model was established in female SD rats. Rats were randomly divided into four groups: the control, untreated PCOS model, Heqi San treated PCOS model (8.1 g/kg) and metformin (MET) treated PCOS model (135 mg/kg) groups. All animals were subcutaneously injected with 6 mg/100 g dehydroepiandrosterone (DHEA) in the neck once a day for 20 consecutive days. The serum hormone levels were measured by ELISA. The ovarian tissues were stained with hematoxylin and eosin (HE) to undergo pathological examination. The expression levels of GLTU4 and PTEN mRNA were examined by real time PCR. The crucial proteins in the PI3K/APT pathway were analyzed by western blotting. Then, the functions of the target genes were analyzed using bioinformatics approaches.ResultsWe found that Heqi San was able to recover the serum hormone levels and improve insulin resistance in PCOS rat model. A morphological lesion of the ovary was also restored with the Heqi San treatment. More importantly, we discovered a correlation between the PI3K/AKT signaling pathway and the beneficial effects of Heqi San, demonstrating that its application could alter the expression levels of p-ERK, p-AKT, p-GSK3β, IRS-1, PTEN and GLTU4, all key factors in the PI3K/APT pathway. Through a bioinformatical analysis, we predicted the related gene function and pathway of the pathological mechanism of PCOS and found miRNAs that are likely to be critical in PCOS occurrence, including rno-miR-144-3p, rno-miR-30c-2-3p, rno-miR-486, rno-miR-3586-3p and rno-miR-146b-5p.ConclusionThe beneficial effects of Heqi on PCOS, including alter serum hormone levels, recover ovary morphological lesions and improve insulin resistance, which is mediated through the PI3K/AKT pathway.Graphical abstractThe potential role of miRNA-144-3p in PCOS pathogenesis.

Troxerutin protects against DHT-induced polycystic ovary syndrome in rats

“…However, there was a significant troxerutin-caused ( 300 mg/kg) decline in serum and hypothalamic GnRH. In regard to the serum hormone levels in rats, many previous studies have reported that LH were generally in the range of 1.5 ~ 3 mIU/ml [32,33], FSH levels varied from 8mIU/ml to 20mIU/ml [22,34]and testosterone varied from 0.2 to 10 ng/ml [32,[34][35][36][37], which were approximately consistent with the corresponding results in the present study. Conclusively, troxerutin treatment 300 kg/mg to rats for up to 4 weeks inhibited the hyperactive GnRH/LH system in PCOS rats.…”

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase

“…PI3K/Akt signaling is a major downstream of insulin signaling that mediates the effect of insulin on glucose and lipid metabolism [28][29][30]. Under the condition of PCOS, PI3K/Akt signaling is usually inhibited [28][29][30].…”

Identification of Epigenetic Interactions between MicroRNA and DNA Methylation Associated with Polycystic Ovarian Syndrome

“…Therefore, these were associated with the NOD-like receptor signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, NF-kappa B signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Th17 cell differentiation, Toll-like receptor signaling pathway, and chemokine signaling pathway. Among these, the MAPK signaling pathway [30], PI3K-Akt signaling pathway [31], and Toll-like receptor signaling pathway [32] had been reported to be involved in PCOS previously by performing apoptosis and cell-proliferation related processes.…”