Gamal Mahmoud, Awad Mohamed A, Shadidizaji Azizeh, Ibrahim Marwa A, Ghoneim Magdy A, Warda Mohamad
Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States.
Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
J Nutr Biochem. 2025 Jan;135:109775. doi: 10.1016/j.jnutbio.2024.109775. Epub 2024 Oct 5.
Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol Hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and Hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an 8-week treatment with either EVOO (90 g/kg of the diet) (DO) or Hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired β-cell function. In contrast, treatments with EVOO and Hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, Hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced β-cell survival. Molecular docking and dynamics confirm Hydroxytyrosol's high affinity binding to PGC-1α, IRE-1α, and PPAR-γ, particularly IRE-1α, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and Hydroxytyrosol. Moreover, the favorable docking scores of Hydroxytyrosol with PGC-1α, IRE-1α, and PPAR-γ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.
特级初榨橄榄油（EVOO）具有假定的抗糖尿病活性，这主要归因于其多酚成分羟基酪醇。在本研究中，我们探究了EVOO和羟基酪醇对体内2型糖尿病（T2D）模拟大鼠模型以及计算机模拟研究的抗糖尿病作用。将Wistar大鼠分为四组。第一组作为正常对照组（NC），而其余组采用高脂饮食（HFD）喂养12周，随后单次注射链脲佐菌素（STZ，30 mg/kg）诱导2型糖尿病（T2D）。一个糖尿病组未接受治疗（DC），而另外两组分别接受8周的EVOO（90 g/kg饲料）（DO）或羟基酪醇（17.3 mg/kg饲料）（DH）治疗。DC组表现出已确诊T2D的标志性特征，包括空腹血糖水平升高、葡萄糖耐量受损、HOMA-IR增加、胰岛素受体表达广泛下调、氧化应激增强以及β细胞功能受损。相比之下，EVOO和羟基酪醇治疗引发了抗糖尿病反应，其特征是葡萄糖耐量改善，表现为血糖清除加速。系统分析揭示了潜在的抗糖尿病机制：两种治疗均增强了肝脏和骨骼肌中胰岛素受体的表达，增加了脂联素水平，并减轻了氧化应激。此外，EVOO降低了细胞内脂质，而羟基酪醇恢复了脂肪组织胰岛素敏感性并增强了β细胞存活。分子对接和动力学证实羟基酪醇与PGC-1α、IRE-1α和PPAR-γ具有高亲和力结合，特别是与IRE-1α，突出了其调节糖尿病信号通路的潜力。总体而言，这些机制突出了EVOO和羟基酪醇假定的抗糖尿病作用。此外，羟基酪醇与PGC-1α、IRE-1α和PPAR-γ的良好对接分数支持了其抗糖尿病潜力，并为进一步研究和开发新型抗糖尿病疗法提供了有希望的途径。
