Abstract The current study aimed to evaluate the in vivo hypoglycemic potential of Myristica fragrans seed extract co-administered with glimepiride in Swiss albino mice. Computational tools were used to further verify the in vivo findings and to help compare this combination to the glimepiride-pioglitazone combination in terms of the binding affinity of the ligands to their respective target protein receptors and the relative stability of the drug-protein complexes. The effect of the combined therapy was observed both in alloxan- and glucose-induced hyperglycemic Swiss albino mice. The mean fasting blood glucose level of the test groups was measured and statistically evaluated using Student’s t test. The combined therapy significantly reduced the blood glucose level in a time-dependent manner compared to glimepiride alone. The binding affinity of glimepiride was found to be −7.6 kcal/mol with sulfonylurea receptor 1 in molecular docking. Conversely, macelignan-peroxisome proliferator-activated receptor (PPAR) α and macelignan-PPAR γ complexes were stabilized with −9.2 and −8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γ complexes were more stable than pioglitazone complexes. The combination shows promise in animal and computer models and requires further trials to provide evidence of its activity in humans.

中文翻译：

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使用肉豆蔻与格列美脲联合治疗 2 型糖尿病的可能替代疗法：体内评估和计算机支持

摘要 目前的研究旨在评估肉豆蔻种子提取物与格列美脲在瑞士白化小鼠体内的降血糖潜力。计算工具用于进一步验证体内发现，并帮助将这种组合与格列美脲-吡格列酮组合在配体与其各自靶蛋白受体的结合亲和力和药物-蛋白质复合物的相对稳定性方面进行比较。在四氧嘧啶和葡萄糖诱导的高血糖瑞士白化小鼠中均观察到联合治疗的效果。使用Student's t检验测量和统计评估测试组的平均空腹血糖水平。与单独使用格列美脲相比，联合治疗以时间依赖性方式显着降低血糖水平。在分子对接中，发现格列美脲与磺酰脲受体 1 的结合亲和力为 -7.6 kcal/mol。相反，肉豆蔻木脂素-过氧化物酶体增殖物激活受体 (PPAR) α 和肉豆蔻木脂素-PPAR γ 复合物分别以 -9.2 和 -8.3 kcal/mol 稳定。分子动力学模拟表明，肉豆蔻木脂素-PPAR α 和γ 复合物比吡格列酮复合物更稳定。这种组合在动物和计算机模型中显示出前景，需要进一步试验以提供其在人体中的活性证据。分子动力学模拟表明，肉豆蔻木脂素-PPAR α 和γ 复合物比吡格列酮复合物更稳定。这种组合在动物和计算机模型中显示出前景，需要进一步试验以提供其在人体中的活性证据。分子动力学模拟表明，肉豆蔻木脂素-PPAR α 和γ 复合物比吡格列酮复合物更稳定。这种组合在动物和计算机模型中显示出前景，需要进一步试验以提供其在人体中的活性证据。