Antidiabetic potential of Mentha piperita essential oil: GC–MS profiling, in vitro, in vivo and in silico analyses

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-10-05 DOI:10.1016/j.molstruc.2025.144239

Elhafnaoui Lanez , Yahia Bekkar , Lotfi Bourougaa , Mohammed Larbi Benamor , Rania Bouraoui , Ouafa Boudebia , Aicha Adaika , Kaouther Nesba , Housseyn Chaoua , Lazhar Bechki , Touhami Lanez , Huda Alsaeedi , Mikhael Bechelany , Ahmed Barhoum

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引用次数: 0

Abstract

In this study, Mentha piperita essential oil (EO) antidiabetic activity was thoroughly investigated using a multidisciplinary approach. Gas chromatography–mass spectrometry (GC–MS) identified some key bioactive compounds, including pulegone, α-terpineol, borneol, linalool acetate, menthone, eucalyptol, and trans-sabinene hydrate. Their relative percentages in the EO (>1 % w/w) were indicative of biological importance. In vitro enzyme inhibitory assays displayed strong inhibitory effects of the EO on the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase and stronger inhibitory action than the standard antidiabetic compound acarbose. In vivo research in diabetic rats induced by alloxan monohydrate reaffirmed the hypoglycemic effect of the EO with the lowering of fasting blood glucose level by 33 % after 14 days of treatment. Molecular docking experiments indicated greater binding affinities of pulegone for α-amylase (ΔG = –5.83 kcal·mol⁻¹) and linalool acetate for α-glucosidase (ΔG = –6.95 kcal·mol⁻¹) compared to acarbose (ΔG = –4.51 and –6.09 kcal·mol⁻¹, respectively). Molecular dynamics simulations also validated the structural stability and optimal interaction dynamics of principal EO components with α-amylase and α-glucosidase. Eucalyptol and linalool acetate possessed minimum root-mean-square deviation (RMSD) and solvent-accessible surface area (SASA) against α-amylase, showing high stability of complex, while α-terpineol and eucalyptol exhibited good binding affinity towards α-glucosidase. MM-PBSA binding free energy calculations revealed that linalool acetate and eucalyptol were the best inhibitory agents for α-amylase (–26.98 and –26.45 kcal·mol⁻¹) and α-glucosidase (–20.41 and –20.71 kcal·mol⁻¹), respectively. DFT analysis also yielded more insight into their electronic properties, reactivity, and stability, further establishing their enzyme inhibition activity. These findings introduce M. piperita EO as a natural agent with α-amylase and α-glucosidase inhibition potential for the management of diabetes and glycemia.

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薄荷精油的抗糖尿病潜力：GC-MS分析，体外，体内和计算机分析

在这项研究中，薄荷精油（EO）的抗糖尿病活性进行了深入研究，采用多学科的方法。气相色谱-质谱联用（GC-MS）鉴定出一些关键的生物活性化合物，包括普莱酮、α-松油醇、冰片、醋酸芳樟醇、薄荷酮、桉油醇和水合反式sabinene。它们在EO中的相对百分比（> 1% w/w）表明了生物重要性。体外酶抑制实验表明，EO对糖水解酶α-淀粉酶和α-葡萄糖苷酶有较强的抑制作用，比标准降糖化合物阿卡波糖的抑制作用更强。对一水四氧嘧啶诱导的糖尿病大鼠的体内研究再次证实了EO的降糖作用，治疗14天后，其空腹血糖水平降低了33%。分子对接实验表明，与阿卡波糖（ΔG = -4.51和-6.09千卡·摩尔⁻¹）相比，普莱酮对α-淀粉酶（ΔG = -5.83千卡·摩尔⁻¹）和乙酸芳樟醇对α-葡萄糖苷酶（ΔG = -6.95千卡·摩尔⁻¹）的结合能力更强。分子动力学模拟还验证了EO主要组分与α-淀粉酶和α-葡萄糖苷酶的结构稳定性和最佳相互作用动力学。桉油醇和乙酸芳樟醇对α-淀粉酶具有最小的均方根偏差（RMSD）和溶剂可及表面积（SASA），具有较高的配合物稳定性，而α-松油醇和桉油醇对α-葡萄糖苷酶具有良好的结合亲和力。MM-PBSA结合自由能计算结果显示，醋酸芳樟醇和桉树醇分别是α-淀粉酶（-26.98和-26.45 kcal·mol⁻¹）和α-葡萄糖苷酶（-20.41和-20.71 kcal·mol⁻¹）的最佳抑制剂。DFT分析还对它们的电子性质、反应性和稳定性有了更深入的了解，进一步确定了它们的酶抑制活性。这些研究结果表明，胡椒毛霉EO是一种具有α-淀粉酶和α-葡萄糖苷酶抑制潜力的天然药物，可用于治疗糖尿病和血糖。

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.