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.
Highlights
Heqi San, a traditional Chinese medicine (TCM) has been reported to regulate hormone levels in patients with metabolic disease, suggesting a potential clinical application
The beneficial effects of Heqi on polycystic ovary syndrome (PCOS), including alter serum hormone levels, recover ovary morphological lesions and improve insulin resistance, which is mediated through the PI3K/AKT pathway
(T) and fasting insulin levels increased after the DHEA injection when compared with control rats (Fig. 1a, b), demonstrating that the established model reflected the primary symptoms of polycystic ovary syndrome
Summary
Heqi San, a traditional Chinese medicine (TCM) has been reported to regulate hormone levels in patients with metabolic disease, suggesting a potential clinical application. We aimed to elucidate the effect of Heqi San on rat model of polycystic ovary syndrome (PCOS). Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with both endocrine and metabolic disorder. It affects approximately 4%–18% of all reproductive-aged women in the world [1, 2]. One of the most widely used medicines for PCOS treatment is metformin, an insulinsensitizing drug [8], which can increase the insulin sensitivity of ovaries to enhance glucose uptake [9]. 3-iodothyronamine was found to reprogram lipid metabolic pathways [10], and
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