Department of Clinical Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
J Steroid Biochem Mol Biol. 2021 Oct;213:105954. doi: 10.1016/j.jsbmb.2021.105954. Epub 2021 Jul 21.
The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS).
Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method.
Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS.
Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.
本研究旨在探讨一种强效多酚，漆黄素，对枸橼酸氯米酚（CC）诱导的多囊卵巢综合征（PCOS）大鼠模型的治疗作用。
将 24 只 42 天大的雌性 Wistar 大鼠分为四组：对照组（给予羧甲基纤维素（CMC 0.5%））、PCOS 组给予枸橼酸氯米酚（1mg/kg）、漆黄素组给予相同剂量的枸橼酸氯米酚+漆黄素（10mg/kg）、二甲双胍组给予相同剂量的枸橼酸氯米酚+二甲双胍（300mg/kg）。实验结束时，分析生化（血糖、血脂谱）和激素（胰岛素、睾酮、雌二醇和孕酮）参数。通过苏木精和伊红（H&E）染色对卵巢进行组织学检查。实时聚合酶链反应（PCR）和蛋白质印迹法用于检测卵巢中细胞色素 P450 17A1（CYP17A1）、沉默调节蛋白 1（SIRT1）和 5'AMP 激活蛋白激酶（AMPK）基因的表达。此外，通过比色法分析卵巢中抗氧化酶包括过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的酶活性。
枸橼酸氯米酚给药导致生化和激素参数明显异常。漆黄素使血糖、血脂谱、稳态模型评估胰岛素抵抗（HOMA-IR）、睾酮、雌二醇和孕酮水平正常化。此外，漆黄素增加了卵巢中 SIRT1 和 AMPK 的表达水平，并降低了 CYP17A1 的表达水平。此外，漆黄素通过增强 CAT、SOD 和 GPx 的抗氧化活性发挥保护作用，这些酶的活性因诱导 PCOS 而耗尽。漆黄素的作用与二甲双胍相当，二甲双胍是治疗 PCOS 的标准药物。
我们的结果表明，漆黄素治疗通过恢复与能量平衡和抗氧化酶相关的关键基因，对 PCOS 诱导的改变产生显著缓解作用，这表明它可能在对抗 PCOS 方面发挥关键作用。
