TY - JOUR T1 - Effects of total flavonoids from Eucommia ulmoides Oliv. leaves on polycystic ovary syndrome with insulin resistance model rats induced by letrozole combined with a high-fat diet. AU - Peng,Meng-Fan, AU - Tian,Shuo, AU - Song,Ya-Gang, AU - Li,Cai-Xia, AU - Miao,Ming-San, AU - Ren,Zhen, AU - Li,Ming, Y1 - 2021/02/19/ PY - 2020/11/20/received PY - 2021/02/09/revised PY - 2021/02/14/accepted PY - 2021/2/23/pubmed PY - 2021/9/25/medline PY - 2021/2/22/entrez KW - Eucommia ulmoides Oliv. leaves KW - Hypothalamus pituitary ovary axis KW - Insulin resistance KW - Polycystic ovary syndrome SP - 113947 EP - 113947 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 273 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. leaves are the dry leaves of Eucommia ulmoides Oliv. Modern studies have shown that Eucommia ulmoides Oliv. leaves and its extracts have many pharmacological effects, such as regulating hypothalamus pituitary ovary (HPO) axis function, estrogen like effects, correcting insulin resistance (IR), regulating lipids, and reducing weight, which are consistent with the clinical manifestations in polycystic ovary syndrome (PCOS) patients. PCOS patients often have HPO axis disorder, low estrogen, high androgen, high IR complication rate, and obesity. Previous preclinical studies have shown that total flavonoids from Eucommia ulmoides Oliv. leaves (TFEL) can improve the imbalance in sex hormone secretion in perimenopausal animal models by regulating the function of the HPO axis. Thus, it is important to understand if flavonoids are the active parts of Eucommia ulmoides Oliv. leaves that interfere with polycystic ovary syndrome with insulin resistance (PCOS-IR), and determine the regulatory role they play in sex hormones and IR? AIM OF THE STUDY: Investigate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the ovary and kisspeptin/insulin like growth factor/leptin receptor1/androgen receptor (Kiss1/IGF-1/LEPR/AR) in the HPO axis to determine the mechanism of TFEL intervention in a rat model of PCOS-IR model rats. MATERIALS AND METHODS: A rat model of PCOS-IR was established using a high-fat diet (49 d) combined with letrozole (1 mg/kg·d, for 28 d). Then, metformin (300 mg/kg·d) and TFEL (220 mg/kg·d, 110 mg/kg·d, and 55 mg/kg·d) were administered continuously for 21 days. At the end of the experiment, samples were taken and the related indexes were measured. RESULTS: TFEL reduced the body weight, Lee's index, ovarian index, ovarian area and ovarian volume, increased serum E2, SHBG levels and ISI, decreased serum levels of T, LEP, INS, and FBG (whole blood), and reduced the HOMA-IR in rats with PCOS-IR. TFEL downregulate Kiss1, IGF-1, and AR in the arcuate nucleus of hypothalamus, and upregulate Kiss1, downregulate IGF-1 and AR in the pituitary gland, and upregulate Kiss1, downregulate IGF-1, LEPR, and AR in the ovary of rats with PCOS-IR. TFEL could downregulate p-IRS-1Ser307, upregulate IRS-1, p-IRS-1Tyr895, PI3Kp85α, p-PI3Kp85α, AKT, p-AKT, and GLUT4 in the ovary, and ameliorated histopathological changes in the ovary and pancreas of rats with PCOS-IR. CONCLUSION: TFEL can inhibit ovarian hyperplasia, regulate disorders of glucose and lipid metabolism and improve the secretion of sex hormones, by regulating the expression of PI3K/AKT signaling pathway-related proteins in the ovary and Kiss1/IGF-1/LEPR/AR in the HPO axis. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/33617969/Effects_of_total_flavonoids_from_Eucommia_ulmoides_Oliv__leaves_on_polycystic_ovary_syndrome_with_insulin_resistance_model_rats_induced_by_letrozole_combined_with_a_high_fat_diet_ DB - PRIME DP - Unbound Medicine ER -