Tallapalli Partha Saradhi, Reddy Yennam Dastagiri, Yaraguppi Deepak A, Matangi Surya Prabha, Challa Ranadheer Reddy, Vallamkonda Bhaskar, Ahmad Sheikh F, Al-Mazroua Haneen A, Rudrapal Mithun, Dintakurthi Sree Naga Bala Krishna Prasanth, Pasala Praveen Kumar
Department of Pharmacology, Santhiram College of Pharmacy, JNTUA, Nandyal 518112, Andhra Pradesh, India.
Department of Biotechnology, KLE Technological University, Hubli 580020, Karnataka, India.
Pharmaceuticals (Basel). 2024 Aug 21;17(8):1093. doi: 10.3390/ph17081093.
This study aimed to compare the effects of β-sitosterol nanoparticles (BETNs) and β-sitosterol (BET) on cognitive impairment, oxidative stress, and inflammation in a myocardial infarction (MI) rat model using in silico and in vivo methods.
β-Sitosterol (BET) and myeloperoxidase (MPO) ligand-receptor binding affinities were evaluated using Autodock Vina for docking and Gromacs for dynamics simulations. BET nanoparticles, prepared via solvent evaporation, had their size confirmed by a nanoparticle analyzer. ISO-induced cognitive impairment in rats was assessed through Morris water maze and Cook's pole climbing tests. Oxidative stress, inflammation, and cardiac injury were evaluated by measuring GSH, SOD, MDA, MPO, CkMB, LDH, lipid profiles, and ECGs. Histopathology of the CA1 hippocampus and myocardial tissue was performed using H&E staining.
In silico analyses revealed strong binding affinities between BET and MPO, suggesting BET's potential anti-inflammatory effect. BETN (119.6 ± 42.6 nm; PDI: 0.809) significantly improved MI-induced cognitive dysfunction in rats ( < 0.001 ***), increased hippocampal GSH ( < 0.01 **) and SOD ( < 0.01 **) levels, and decreased hippocampal MDA ( < 0.05 *) and MPO levels ( < 0.01 **). BETNs also elevated cardiac GSH ( < 0.01 **) and SOD ( < 0.01 **) levels and reduced cardiac MPO ( < 0.01 **), CkMB ( < 0.001 **) and LDH ( < 0.001 **) levels. It restored lipid profiles, normalized ECG patterns, and improved histology in the hippocampal CA1 region and myocardium.
Compared with BET treatment, BETNs were more effective in improving cognitive impairment, oxidative damage, and inflammation in MI rats, suggesting its potential in treating cognitive dysfunction and associated pathological changes in MI.
本研究旨在采用计算机模拟和体内实验方法，比较β-谷甾醇纳米颗粒（BETNs）和β-谷甾醇（BET）对心肌梗死（MI）大鼠模型认知功能障碍、氧化应激和炎症的影响。
使用Autodock Vina进行对接和Gromacs进行动力学模拟，评估β-谷甾醇（BET）与髓过氧化物酶（MPO）的配体-受体结合亲和力。通过溶剂蒸发法制备的BET纳米颗粒，其尺寸由纳米颗粒分析仪确认。通过莫里斯水迷宫和库克爬杆试验评估ISO诱导的大鼠认知功能障碍。通过测量谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、髓过氧化物酶（MPO）、肌酸激酶同工酶（CkMB）、乳酸脱氢酶（LDH）、血脂谱和心电图来评估氧化应激、炎症和心脏损伤。使用苏木精-伊红（H&E）染色对海马CA1区和心肌组织进行组织病理学检查。
计算机模拟分析显示BET与MPO之间具有较强的结合亲和力，表明BET具有潜在的抗炎作用。BETN（119.6±42.6nm；多分散指数：0.809）显著改善了MI诱导的大鼠认知功能障碍（P<0.001 ***），提高了海马GSH（P<0.01 **）和SOD（P<0.01 **）水平，降低了海马MDA（P<0.05 *）和MPO水平（P<0.01 **）。BETN还提高了心脏GSH（P<0.01 **）和SOD（P<0.01 **）水平，降低了心脏MPO（P<0.01 **）、CkMB（P<0.001 **）和LDH（P<0.001 **）水平。它恢复了血脂谱，使心电图模式正常化，并改善了海马CA1区和心肌的组织学。
与BET治疗相比，BETN在改善MI大鼠的认知功能障碍、氧化损伤和炎症方面更有效，表明其在治疗MI认知功能障碍及相关病理变化方面具有潜在作用。
