El Zanaty Shaimaa A, El Wafa Salwa A Abu, Hussein Mohammed A, El Gizawy Heba A, Temraz Abeer
Department of Pharmacognosy, Faculty of Pharmacy, October 6 University (O6U), 6th of October City, 12585, Giza, Egypt.
Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11754, Egypt.
Sci Rep. 2025 Sep 12;15(1):32454. doi: 10.1038/s41598-025-18116-5.
Polycystic ovary syndrome; is a prevalent endocrine disorder, characterized by hormonal imbalances, inflammation, and oxidative stress. Natural remedies, including Murcott and Merav (Citrus reticulata varieties, Family: Rutaceae) fruits and leaves extracts, have demonstrated promising therapeutic effects in alleviating these symptoms. This study aimed to evaluate the efficacy of these extracts concerning their metabolomics in modulating hormonal levels, enhancing lipid metabolism while alleviating inflammation and oxidative stress in mice with polycystic ovary syndrome through the regulation of miR-33b-5P and miR-145 gene expression. UPLC-T-TOF-MS/MS analysis identified and quantified One hundred-seven bioactive metabolites. These metabolites were categorized into various classes according to their chemical structures, including phenolic types such as 68 flavonoids, 4 coumarins and 7 phenolic acids in addition to, 3 nitrogenous compounds, 7 terpenes and terpenoids, 6 fatty acids and their conjugates and 12 miscellaneous compounds. and various biochemical assays were performed. Blood samples were collected to measure plasma FSH, testosterone, LH, and lipid profiles. Oxidative stress biomarkers, including malondialdehyde (MDA) and superoxide dismutase (SOD), and COX-2 and NF-kB levels were assessed using ELISA kits. Micro-RNA gene expression, miR-33b-5P and miR-145, related to inflammation and oxidative stress, was analyzed using qRT-PCR. Ovarian tissues were examined histologically to assess morphological changes. These findings highlight that Murcott and Merav extracts could be a promising alternative natural treatment for PCOS, balancing hormonal levels, improving lipid profiles, and reducing inflammation and oxidative stress. Merav leaves emerged as the most promising candidate for PCOS therapy, attributed to their high levels of methylated kaempferol, a key bioactive flavonoid.
多囊卵巢综合征是一种常见的内分泌紊乱疾病，其特征为激素失衡、炎症和氧化应激。包括默科特柑橘和梅拉夫柑橘（柑橘属品种，芸香科）果实及叶片提取物在内的天然疗法，已在缓解这些症状方面显示出有前景的治疗效果。本研究旨在评估这些提取物在调节激素水平、增强脂质代谢、同时通过调控miR-33b-5P和miR-145基因表达减轻多囊卵巢综合征小鼠炎症和氧化应激方面的代谢组学功效。超高效液相色谱-串联飞行时间质谱分析鉴定并定量了107种生物活性代谢物。这些代谢物根据其化学结构被分类为不同类别，包括酚类，如68种黄酮类、4种香豆素和7种酚酸，此外还有3种含氮化合物、7种萜类和萜烯类、6种脂肪酸及其共轭物以及12种其他化合物。并进行了各种生化测定。采集血样以测量血浆促卵泡生成素、睾酮、促黄体生成素和脂质谱。使用酶联免疫吸附测定试剂盒评估氧化应激生物标志物，包括丙二醛（MDA）和超氧化物歧化酶（SOD），以及环氧合酶-2（COX-2）和核因子κB（NF-κB）水平。使用定量逆转录聚合酶链反应分析与炎症和氧化应激相关的微小RNA基因表达，即miR-33b-5P和miR-145。对卵巢组织进行组织学检查以评估形态学变化。这些发现突出表明，默科特柑橘和梅拉夫柑橘提取物可能是多囊卵巢综合征一种有前景的替代性天然治疗方法，可平衡激素水平、改善脂质谱并减轻炎症和氧化应激。梅拉夫柑橘叶成为多囊卵巢综合征治疗最有前景的候选物，这归因于其高水平的甲基化山奈酚，一种关键的生物活性黄酮类化合物。
