Shahbaz Saliha, Sharif Ali, Akhtar Bushra, Mobashar Aisha, Shazly Gamal A, Metouekel Amira, Bourhia Mohammed
Department of Pharmacology, Faculty of Pharmaceutical and Allied Health Sciences, Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan.
Department of Pharmacy, University of Agriculture Faisalabad, Faisalabad, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec 23. doi: 10.1007/s00210-024-03720-5.
Polycystic ovarian syndrome is a heterogeneous endocrine disorder characterized by ovarian cysts, anovulation, endocrine variations, which includes oligo-amenorrhea along with associated subfertility and hyperandrogenism manifested as acne, hirsutism, and male-pattern alopecia. Coumarins are fused benzene and pyrone ring systems that exhibit a wide spectrum of bioactivities. This study aimed to investigate the effects of 3-acetyl coumarin (3-AC) on polycystic ovarian syndrome in female rats. Acute oral toxicity conducted according to OECD guidelines 425 (a test conducted in scenarios where there is information indicating that the test material is non-toxic) exhibited no mortality. In vitro DPPH assay demonstrated anti-oxidant potential of 3-AC. Letrozole, a nonsteroidal aromatase inhibitor was used to induce PCOS (1 mg/kg-21 days). Normal and PCOS control rats were administered a vehicle solution (0.5% CMC), whereas 3-AC (10, 20, and 30 mg/kg) and metformin (300 mg/kg) was administered to treatment groups for 15 days. Vaginal smears were taken to assess estrous cycle. Rats were euthanized at day 37. In vivo analysis included measurement of fasting blood glucose, total-cholesterol, triglycerides, FSH, LH, and testosterone levels. ELISA was used for measurement of inflammatory markers (IL-1β, IL-6, and TNF-α). Oxidative stress markers (SOD, CAT, GSH, MDA, NO) were also evaluated. Expression levels of NF-κB and LHCGR were detected by RT-qPCR. Molecular docking was also performed. One-way analysis of variance was employed followed by Tukey's test for statistical analysis. Treatment with 3-AC led to favorable effects in PCOS rats. Specifically, inflammatory levels, antioxidant status, lipid profile, and glucose concentrations were all improved. These findings suggest that 3-acetyl coumarin (3-AC) may serve as a promising therapeutic agent for alleviating symptoms of PCOS in this animal model.
多囊卵巢综合征是一种异质性内分泌疾病，其特征为卵巢囊肿、无排卵、内分泌变化，包括月经稀发以及相关的生育力低下和高雄激素血症，表现为痤疮、多毛症和男性型脱发。香豆素是由苯环和吡喃环稠合而成的体系，具有广泛的生物活性。本研究旨在探讨3-乙酰香豆素（3-AC）对雌性大鼠多囊卵巢综合征的影响。根据经合组织准则425进行的急性经口毒性试验（在有信息表明受试物质无毒的情况下进行的试验）未出现死亡情况。体外DPPH试验证明了3-AC的抗氧化潜力。来曲唑，一种非甾体芳香化酶抑制剂，被用于诱导多囊卵巢综合征（1毫克/千克，连续21天）。正常大鼠和多囊卵巢综合征对照大鼠给予赋形剂溶液（0.5%羧甲基纤维素），而治疗组给予3-AC（10、20和30毫克/千克）和二甲双胍（300毫克/千克），持续15天。采集阴道涂片以评估发情周期。在第37天对大鼠实施安乐死。体内分析包括测量空腹血糖、总胆固醇、甘油三酯、促卵泡生成素、促黄体生成素和睾酮水平。采用酶联免疫吸附测定法测量炎症标志物（白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α）。还评估了氧化应激标志物（超氧化物歧化酶、过氧化氢酶、谷胱甘肽、丙二醛、一氧化氮）。通过逆转录定量聚合酶链反应检测核因子-κB和促黄体生成素/绒毛膜促性腺激素受体的表达水平。还进行了分子对接。采用单因素方差分析，随后进行Tukey检验进行统计分析。用3-AC治疗对多囊卵巢综合征大鼠产生了有益效果。具体而言，炎症水平、抗氧化状态及血脂和血糖浓度均得到改善。这些发现表明，3-乙酰香豆素（3-AC）可能是一种有前景的治疗药物，可缓解该动物模型中多囊卵巢综合征的症状。
