Elashmony Sahar M, Alhindi Yosra, Merzeban Dina H, Mohammed Rehab A, Elsayed Asmaa Mohamed, Sofi Marwa A, Mahmoud Rania H, Shamardl Hanan A, Shaker Dina Elsayed
Medical Pharmacology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Pharmacology and Toxicology Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Sci Rep. 2025 Sep 15;15(1):32554. doi: 10.1038/s41598-025-16925-2.
Metabolic syndrome (MetS) is a widespread, complex health issue that poses a substantial global health burden with increased healthcare costs and reduced quality of life, necessitating effective prevention and management strategies. This study aimed to investigate the potential therapeutic effects of cranberry extract (Vaccinium macrocarpon) and metformin on metabolic syndrome in a rat model. Forty rats were divided into the following groups: normal control, MetS (high fat and fructose for 4 weeks followed by streptozotocin 35 mg/kg, i.p.), MetS + cranberry (50 mg/kg), MetS + cranberry (100 mg/kg), and MetS + metformin (200 mg/kg) groups. Treatments were given orally for four weeks with the continuation of a high-fat and high-fructose diet. The evaluations included key metabolic parameters, liver and kidney pathology, and relevant molecular pathways. The present results revealed that MetS induction significantly increased body weight, BMI, fasting glucose, and OGTT results; impaired lipid profile, creatinine and blood pressure; and upregulated hepatic gene expression of Rho-associated protein kinase 1 (Rock1 ) and sterol regulatory element-binding transcription factor 1 (Srebf1), which encodes the protein SREBP-1c. In addition to hepatic and renal structural abnormalities, increased collagen and increased iNOS/TGF-β1 immunoreactivity were observed. Cranberry ameliorated metabolic parameters in a dose-dependent manner, upregulated adenosine monophosphate-activated protein kinase (AMPK), downregulated Rock1 and Srebf1 expression, improved the histopathology of the liver and kidney and decreased the immunoexpression of iNOS and TGF-β1. The results for cranberry were generally comparable to those for metformin. In conclusion, cranberry extract is potentially a safe therapeutic strategy for MetS, offering broad-spectrum action, organ protection, and molecular pathway modulation. These findings strongly support cranberry as a promising natural approach for managing MetS.
代谢综合征（MetS）是一个广泛存在的复杂健康问题，给全球带来了巨大的健康负担，导致医疗成本增加和生活质量下降，因此需要有效的预防和管理策略。本研究旨在探讨蔓越莓提取物（大果越桔）和二甲双胍对大鼠代谢综合征模型的潜在治疗作用。40只大鼠被分为以下几组：正常对照组、MetS组（高脂高糖饮食4周后腹腔注射链脲佐菌素35mg/kg）、MetS+蔓越莓（50mg/kg）组、MetS+蔓越莓（100mg/kg）组和MetS+二甲双胍（200mg/kg）组。在持续高脂高糖饮食的情况下，口服给药4周。评估内容包括关键代谢参数、肝肾病理学以及相关分子途径。目前的结果显示，诱导MetS显著增加了体重、体重指数、空腹血糖和口服葡萄糖耐量试验结果；损害了血脂、肌酐和血压；上调了Rho相关蛋白激酶1（Rock1）和甾醇调节元件结合转录因子1（Srebf1，其编码蛋白SREBP-1c）的肝脏基因表达。除了肝肾结构异常外，还观察到胶原蛋白增加以及诱导型一氧化氮合酶/转化生长因子-β1免疫反应性增加。蔓越莓以剂量依赖的方式改善了代谢参数，上调了腺苷单磷酸激活蛋白激酶（AMPK），下调了Rock1和Srebf1的表达，改善了肝肾组织病理学，并降低了诱导型一氧化氮合酶和转化生长因子-β1的免疫表达。蔓越莓的结果总体上与二甲双胍相当。总之，蔓越莓提取物可能是一种治疗MetS的安全策略，具有广谱作用、器官保护和分子途径调节作用。这些发现有力地支持了蔓越莓作为一种有前景的管理MetS的天然方法。
