Das Ashmita, Manna Rahul, Chowdhury Durlav, Sharma Dilip, Bodakhe Surendra H
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, India.
Institute of Post Graduate Medical Education and Research, Kolkata, India.
Metab Brain Dis. 2025 Apr 17;40(5):187. doi: 10.1007/s11011-025-01606-w.
This study highlights the potential therapeutic benefits of oxymatrine (OMT), a quinolizidine alkaloid found in Sophora flavescens, for Alzheimer's disease (AD). This study connects the dots between metabolic and neuronal origins by exploring the effects of oxymatrine in slowing down hypercholesterolemic and fibrotic changes that contribute to cognitive deficits. In our study, laboratory rats were fed a high-cholesterol diet for eight weeks. Cognitive abilities were assessed weekly using Hebb's Williams Maze and Radial arm mazes. Additionally, intraperitoneal doses of OMT were administered (20 mg/kg, 40 mg/kg, and 80 mg/kg) for 21 days. Furthermore, using ELISA, plasma and brain oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase- 9, claudin- 5, and ATP Binding Cassette Transporter A1 levels were measured biweekly. High-density lipoprotein, low-density lipoprotein, aspartate aminotransferase, and alanine transaminase levels were estimated using diagnostic kits. The findings demonstrate that The administration of oxymatrine to experimental animals resulted in a dose-dependent synergistic decline in several biomarkers, including oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase- 9, low-density lipoprotein, aspartate aminotransferase, and alanine transaminase levels. At the same time, a concomitant increase in the levels of Claudin- 5, ATP Binding Cassette transporter A1, high-density lipoprotein, and antioxidants in the same animals was observed, especially at a dose of 80 mg/kg. This study aims to establish a link between metabolic and neural origins by investigating the effects of oxymatrine in reducing the progression of hypercholesterolemia and fibrosis, which contribute to cognitive impairment in AD. The research explores how oxymatrine regulates mediators involved in oxysterol production and fibrotic alterations in AD. Preliminary results suggest that oxymatrine has the potential to significantly delay the development and progression of AD, offering a promising treatment alternative for those affected by the disease. The findings of the present study strongly suggest that OMT effectively retards the progression of AD, which is commonly associated with the intake of high-cholesterol diets. Subsequent investigations ought to examine the molecular mechanisms behind oxymatrine's interaction with oxysterols and lipid metabolism, including sophisticated imaging methodologies and metabolomics. Longitudinal studies are essential to evaluate the long-term efficacy and safety of oxymatrine in both animal models and people. Exploring its possible synergistic effects with current medications may yield more effective therapeutic techniques. Identifying biomarkers for personalised medication may also be beneficial. Clinical trials and research on oxymatrine's potential as a prophylactic medication may yield significant insights.
本研究强调了氧化苦参碱(OMT)——一种从苦参中提取的喹诺里西啶生物碱——对阿尔茨海默病(AD)潜在的治疗益处。本研究通过探索氧化苦参碱在减缓导致认知缺陷的高胆固醇血症和纤维化变化方面的作用,将代谢起源与神经元起源联系起来。在我们的研究中,给实验大鼠喂食高胆固醇饮食八周。每周使用赫布威廉姆斯迷宫和放射状臂迷宫评估认知能力。此外,腹腔注射氧化苦参碱(20毫克/千克、40毫克/千克和80毫克/千克),持续21天。此外,每两周使用酶联免疫吸附测定法(ELISA)测量血浆和脑内的氧化甾醇、转化生长因子β、淀粉样蛋白β、基质金属蛋白酶-9、闭合蛋白-5和ATP结合盒转运蛋白A1水平。使用诊断试剂盒估算高密度脂蛋白、低密度脂蛋白、天冬氨酸转氨酶和丙氨酸转氨酶水平。研究结果表明,给实验动物施用氧化苦参碱会导致几种生物标志物呈剂量依赖性协同下降,包括氧化甾醇、转化生长因子β、淀粉样蛋白β、基质金属蛋白酶-9、低密度脂蛋白、天冬氨酸转氨酶和丙氨酸转氨酶水平。同时,观察到同一批动物体内闭合蛋白-5、ATP结合盒转运蛋白A1、高密度脂蛋白和抗氧化剂水平相应增加,尤其是在剂量为80毫克/千克时。本研究旨在通过研究氧化苦参碱在减轻高胆固醇血症和纤维化进展方面的作用,建立代谢起源与神经起源之间的联系,而高胆固醇血症和纤维化会导致AD中的认知障碍。该研究探索了氧化苦参碱如何调节AD中参与氧化甾醇产生和纤维化改变的介质。初步结果表明,氧化苦参碱有可能显著延缓AD的发展和进展,为该病患者提供一种有前景的治疗选择。本研究结果有力地表明,氧化苦参碱能有效延缓AD的进展,而AD通常与高胆固醇饮食的摄入有关。后续研究应该探究氧化苦参碱与氧化甾醇及脂质代谢相互作用背后的分子机制,包括复杂的成像方法和代谢组学。纵向研究对于评估氧化苦参碱在动物模型和人类中的长期疗效和安全性至关重要。探索其与现有药物可能的协同作用可能会产生更有效的治疗技术。确定个性化用药的生物标志物可能也有益处。关于氧化苦参碱作为预防药物潜力的临床试验和研究可能会产生重要见解。