The role of serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome

Abstract

Objective To study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS). Methods Selected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine. Results In the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells. Conclusion In this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.

Short‐term rapamycin administration elevated testosterone levels and exacerbated reproductive disorder in dehydroepiandrosterone‐induced polycystic ovary syndrome mice

“…mTOR expression in granulosa cells of PCOS patients has also been investigated. A recent study showed that granulosa cells of PCOS patients had higher mTOR expression and phosphorylation than those of non PCOS patients; this mTOR expression could be reduced by berberine, a quaternary compound extracted from plants regulating glucose metabolism [ 20 ]. Another study found that mTOR expression in luteal granulosa cells was similar in PCOS patients and healthy individuals, but it was less in luteal granulosa cells in PCOS patients than in controls upon stimulation with insulin [ 13 ].…”

The Potential Effect of Rhizoma coptidis on Polycystic Ovary Syndrome Based on Network Pharmacology and Molecular Docking

“…Berberine has been found to be safe and effective in terms of improving insulin resistance (IR), increasing ovulation rate per cycle, increasing the live birth rate, lowering body weight, and improving blood lipids [ 24 ]. Berberine can treat PCOS by regulating insulin signaling pathway and increasing insulin sensitivity [ 25 ]. Berberine also has the potential to treat PCOS of rat model through upregulating GLUT4 via activating PI3K/AKT and suppressing MAPK pathway [ 26 ].…”

Expression of genes involved in the inflammatory response in human granulosa cells in short-term in vitro culture

“…Kuang et al in their study investigated the effect and mechanism of inflammatory cytokines in serum (including IL6) on PCOS sensitivity to insulin. Women with PCOS were affected by subclinical inflammation leading to insulin resistance contributing to abnormal ovulation and problems with fertilization [28]. Overexpression of this gene is also noticeable in malignant tumors of the ovaries, e.g.…”