Therapeutic Effects of Althaea officinalis L. and Metformin on Estradiol-Induced Polycystic Ovary Syndrome in Rats: Insights into The PI3K/AKT Pathway, Inflammation, and Oxidative Stress.

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Polycystic ovary syndrome (PCOS) is one of the most important causes of infertility, irregular menstrual cycles, and anovulation in women. The current study aimed to investigate the therapeutic effects of Althaea officinalis L. (A. officinale) extract on PCOS in rats. In this experimental study, 70 rats in 7 groups (n=10/group) were studied for three weeks as follows; healthy control (HC), patient (PCOS), metformin (PCOS+MET), A. officinale treatment (PCOS+250 and 500 mg/kg A. officinale) and synergistic (PCOS+MET+250 and 500 mg/kg A. officinale) groups. Luteinizing hormone (LH), folliclestimulating hormone (FSH), progesterone (P) and testosterone (T) levels as well as inflammatory cytokines were measured. Total antioxidant capacity and lipid peroxidation levels were analyzed in ovarian tissue. The expression of GLUT-4, AKT, PI3K, PTEN genes and Ki-67 was assessed by real-time polymerase chain reaction (PCR) and immunohistochemistry, respectively. A. officinale alone and especially in combination with MET moderated inflammatory and antioxidant parameters compared to the PCOS and MET groups. A. officinale in synergistic groups increased the apoptosis of granulosa cells by activating the PI3K/AKT pathway, resulting in a rise in the number of Ki-67 positive cells (P<0.05). Furthermore, following A. officinale treatment the LH/FSH rate decreased and FSH and P increased (P<0.05). Also, A. officinale extract could effectively normalize estrus cycle duration close to the normal group. The extract of A. officinale, in combination with metformin, can enhance the hypothalamic-pituitaryovary (HPO) axis with synergistic anti-inflammatory and antioxidant effects. Additionally, the extract showed apoptotic effect on cystic granulosa cells.