Ibrahim Yasmine F, Alorabi Mohammed, Abdelzaher Walaa Yehia, Toni Nisreen Dm, Thabet Khaled, Hegazy AbdelRahman, Bahaa Haitham Ahmed, Batiha Gaber El-Saber, Welson Nermeen N, Morsy Mohamed A, Venugopala Katharigatta N, Abdel-Aziz Asmaa Mohamed
Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.
Department of Biotechnology, College of Sciences, Taif University, P.O.Box 11099, Taif 21944, Saudi Arabia.
Biomed Pharmacother. 2022 May;149:112870. doi: 10.1016/j.biopha.2022.112870. Epub 2022 Apr 1.
Polycystic ovary syndrome (PCOS) is the most common gynaecological endocrine disease that causes anovulatory infertility. The current study aimed to explore the possible role of diacerein (DIA), an IL-1β inhibitor, in treating letrozole-induced PCOS in rats that exhibit the metabolic and endocrinal criteria of PCOS patients. PCOS was induced in female Wistar rats by the oral administration of letrozole (1 mg/kg, per orally, p.o.) for 21 days. Rats were then treated with DIA (25 mg/kg/day, p.o.), DIA (50 mg/kg/day, p.o.), or metformin (2 mg/100 g/day, p.o.) for 14 days after the PCOS induction. PCOS resulted in a significantly higher body weight, ovarian weight, ovarian size, and cysts, as well as an elevation in serum testosterone, LH, insulin, glycemia, and lipid profile levels. All of these effects were significantly reduced by the DIA administration. Additionally, DIA remarkably inhibited the letrozole-induced oxidative stress in the ovaries, muscles, and liver by reducing the upraised levels of malondialdehyde and total nitrite and increasing the suppressed levels of superoxide dismutase and catalase. DIA enhanced the protective proteins Keap-1, Nrf2, and OH-1 levels. Finally, DIA inhibited the elevated mRNA levels of NLRP3 and caspase-1, the up-regulated inflammatory cytokines IL-6, TNF-α, and the IL-1β/NFκB signaling pathway. Our results proved that DIA ameliorates letrozole-induced PCOS through its antioxidant and anti-inflammatory properties.
多囊卵巢综合征（PCOS）是导致无排卵性不孕的最常见妇科内分泌疾病。本研究旨在探讨白藜芦醇（DIA）（一种IL - 1β抑制剂）在治疗来曲唑诱导的PCOS大鼠中的可能作用，这些大鼠表现出PCOS患者的代谢和内分泌标准。通过口服来曲唑（1 mg/kg，口服，p.o.）连续21天诱导雌性Wistar大鼠患PCOS。在PCOS诱导后，大鼠分别用DIA（25 mg/kg/天，p.o.）、DIA（50 mg/kg/天，p.o.）或二甲双胍（2 mg/100 g/天，p.o.）治疗14天。PCOS导致体重、卵巢重量、卵巢大小和囊肿显著增加，同时血清睾酮、促黄体生成素（LH）、胰岛素、血糖和血脂水平升高。给予DIA后，所有这些影响均显著降低。此外，DIA通过降低升高的丙二醛和总亚硝酸盐水平以及增加超氧化物歧化酶和过氧化氢酶被抑制的水平，显著抑制来曲唑诱导的卵巢、肌肉和肝脏中的氧化应激。DIA提高了保护性蛋白Keap - 1、Nrf2和OH - 1的水平。最后，DIA抑制了NLRP3和caspase - 1的mRNA水平升高、炎症细胞因子IL - 6、TNF - α的上调以及IL - 1β/NFκB信号通路。我们的结果证明，DIA通过其抗氧化和抗炎特性改善来曲唑诱导的PCOS。
