Sen Karishma, Sakarwal Anita, Kumar Kamlesh, Ram Heera, Singh Garima, Kumar Vikas, Panwar Anil, Yadav Mukesh Kumar, Wang Jing-Hua
Department of Zoology, Jai Narain Vyas University, Jodhpur, Rajasthan, 34200, India.
Department of Botany, Pachhunga University College, Aizawl, Mizoram, India.
J Comput Aided Mol Des. 2025 Jun 14;39(1):30. doi: 10.1007/s10822-025-00609-0.
Diabetes often leads to neurodegenerative complications that complicate treatment. Exploring dietary components with neuroprotective properties could offer new therapeutic avenues. This study aimed to evaluate the neuroprotective potential of β-sitosterol against diabetes-associated neurodegenerative complications using a combined in silico and in vivo approach. β-Sitosterol exhibited significant neuroprotective effects in a diabetic neuropathy model. Compared to sitagliptin, β-sitosterol demonstrated stronger binding affinities to DPP4, acetylcholinesterase, and butyrylcholinesterase, along with more stable molecular dynamics profiles. In vivo, β-sitosterol treatment markedly improved glucose tolerance, insulin sensitivity, lipid profiles, and antioxidant capacity. Histological analysis revealed reduced neurodegenerative changes and enhanced neuronal integrity in the cortex and hippocampus. These findings suggest β-sitosterol as a promising therapeutic agent for managing diabetic neurodegeneration, warranting further research and potential clinical application.
糖尿病常导致神经退行性并发症，使治疗变得复杂。探索具有神经保护特性的饮食成分可能提供新的治疗途径。本研究旨在采用计算机模拟和体内实验相结合的方法，评估β-谷甾醇对糖尿病相关神经退行性并发症的神经保护潜力。β-谷甾醇在糖尿病神经病变模型中表现出显著的神经保护作用。与西他列汀相比，β-谷甾醇对二肽基肽酶4（DPP4）、乙酰胆碱酯酶和丁酰胆碱酯酶表现出更强的结合亲和力，以及更稳定的分子动力学特征。在体内，β-谷甾醇治疗显著改善了葡萄糖耐量、胰岛素敏感性、血脂谱和抗氧化能力。组织学分析显示，皮质和海马体中的神经退行性变化减少，神经元完整性增强。这些发现表明β-谷甾醇是治疗糖尿病神经退行性变的一种有前景的治疗药物，值得进一步研究和潜在的临床应用。
