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Background Heqi 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). Method PCOS 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. Results We 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. Conclusion The 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 abstract The potential role of miRNA-144-3p in PCOS pathogenesis.

Background Heqi San has shown therapeutic potential in the treatment of diabetes. This study aimed to explore the mechanism underlying the effects of Heqi San in treating rats with diabetic atherosclerosis (AS). Methods We established a model of atherosclerosis in diabetic rats and treated them with Heqi San. Body weight, food intake, and water intake were measured every two weeks. Subsequently, we examined the effects of Heqi San on serum biochemical markers, aortic structure, fat accumulation, and serum levels of inflammatory factors. The levels of p-AMPK and AMPK in thoracic aorta tissue were evaluated by western blotting. Mass spectrometry was used to identify differential serum metabolites after Heqi San treatment. Results Intragastric administration of Heqi San enhanced food intake and reduced the excessive water intake caused by diabetic atherosclerosis. Both low and high doses of Heqi San decreased elevated levels of TG, TC, LDL, GLU, and insulin, while increasing HDL levels. Additionally, the AS group showed increased expression of CD68 and CCL-2 in thoracic aorta tissue, along with elevated serum levels of IL-6, IL-1β, and TNF-α. Treatment with Heqi San reduced these inflammatory markers. Heqi San also increased p-AMPK expression in thoracic aorta tissue. Mass spectrometry analysis revealed that the AS group had significantly elevated serum levels of L-NIL, Gln_Cys_Asp, and Geshoidin, whereas high-dose Heqi San treatment decreased the levels of these metabolites. Conclusions Heqi San could alleviate atherosclerosis in diabetic rats, and this effect may be associated with changes in serum metabolites such as L-NIL, Gln_Cys_Asp, and Geshoidin.