Loukili El Hassania, Fadil Mouhcine, Elrherabi Amal, Er-Rajy Mohammed, Taibi Mohamed, Azzaoui Khalil, Salghi Rachid, Sabbahi Rachid, Alanazi Mohammed M, Rhazi Larbi, Széchenyi Aleksandar, Siaj Mohamed, Hammouti Belkheir
Euromed University of Fes, UMEF, Fes, Morocco.
Laboratory of Applied Organic Chemistry, Faculty of Sciences and Techniques, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Front Pharmacol. 2025 Mar 10;16:1522124. doi: 10.3389/fphar.2025.1522124. eCollection 2025.
The increasing demand for natural alternatives in diabetes treatment has driven research into plant-derived metabolites, particularly essential oils (EOs) with bioactive properties. This study aims to optimize an EO mixture for inhibiting two key enzymes involved in glucose digestion: pancreatic α-amylase and intestinal α-glucosidase.
Essential oils were extracted from three Moroccan medicinal plants: false yellowhead ( L.), rose geranium ( L'Hér.), and lemongrass ( (DC.) Stapf.). Gas chromatography-mass spectrometry (GC-MS) analysis identified key metabolites in each EO. A statistical mixture design was employed to evaluate different EO ratios for their inhibitory effects on α-amylase and α-glucosidase. Additionally, density functional theory (DFT) calculations and molecular docking simulations were conducted to assess the key metabolites' electronic properties and interaction potential with target enzymes.
GC-MS analysis identified 32 metabolites in . , with citronellol (18.67%), eucalyptol (13.30%), and 2-octen-1-ol (8.12%) as major components. . contained 18 metabolites, dominated by 2-camphanol acetate (51.12%) and camphol (19.32%), while had 23 metabolites, with α-citral (24.70%) and 2-isopropenyl-5-methylhex-4-enal (29.25%) as key constituents. The optimal formulation for α-glucosidase inhibition was a binary mixture of 73% and 27% . In contrast, the best blend for α-amylase inhibition consisted of 56% and 44% . DFT calculations confirmed the electrophilic nature of key metabolites, supporting their potential for enzyme interaction. Molecular docking simulations suggested that these phytochemicals could exhibit stronger inhibitory effects than acarbose, a widely used antidiabetic drug.
These findings highlight the potential of optimized EO formulations as natural alternatives for managing hyperglycemia and developing novel diabetes therapies.
糖尿病治疗中对天然替代物的需求不断增加，推动了对植物源代谢物的研究，特别是具有生物活性的精油（EOs）。本研究旨在优化一种EO混合物，以抑制参与葡萄糖消化的两种关键酶：胰腺α-淀粉酶和肠道α-葡萄糖苷酶。
从三种摩洛哥药用植物中提取精油：假金盏花（L.）、玫瑰天竺葵（L'Hér.）和柠檬草（（DC.）Stapf.）。气相色谱-质谱（GC-MS）分析确定了每种EO中的关键代谢物。采用统计混合设计评估不同EO比例对α-淀粉酶和α-葡萄糖苷酶的抑制作用。此外，进行了密度泛函理论（DFT）计算和分子对接模拟，以评估关键代谢物的电子性质及其与靶酶的相互作用潜力。
GC-MS分析在假金盏花中鉴定出32种代谢物，其中香茅醇（18.67%）、桉叶油素（13.30%）和2-辛烯-1-醇（8.12%）为主要成分。玫瑰天竺葵含有18种代谢物，以乙酸异龙脑酯（51.12%）和龙脑（19.32%）为主，而柠檬草有23种代谢物，以α-柠檬醛（24.70%）和2-异丙烯基-5-甲基己-4-烯醛（29.25%）为关键成分。抑制α-葡萄糖苷酶的最佳配方是73%的玫瑰天竺葵和27%的柠檬草的二元混合物。相比之下，抑制α-淀粉酶的最佳混合物由56%的假金盏花和44%的玫瑰天竺葵组成。DFT计算证实了关键代谢物的亲电性质，支持了它们与酶相互作用的潜力。分子对接模拟表明，这些植物化学物质可能比广泛使用的抗糖尿病药物阿卡波糖表现出更强的抑制作用。
这些发现突出了优化的EO配方作为控制高血糖和开发新型糖尿病疗法的天然替代物的潜力。
