Applied Science Department, Indian Institute of Information Technology, Allahabad, UP, India.
J Biomol Struct Dyn. 2023 Jul;41(10):4485-4503. doi: 10.1080/07391102.2022.2068072. Epub 2022 May 1.
Microorganisms in human gastrointestinal tract have profound influence on the transformation of food into metabolites which can impact human health. Along with playing crucial roles in regulating and modulating various metabolic reactions and life processes, dysbiosis of gut microbiota also affects the permeability of gut and blood-brain barrier. This increases the chance of age-related neurological disorders' like Alzheimer's and Parkinson's diseases. () has been proclaimed as a virtuous plant for the treatment of neurodegenerative diseases and many other problems. We have studied the bioactive components of for combined treatment of gut-dysbiosis led bowel diseases (Inflammatory Bowel Disease, Irritable Bowel Syndrome) and the most common neurodegenerative diseases through common potential targets. This approach can solve along with curing the neurodegenerative diseases, the factors causing these diseases would also be obstructed from entering the brain, consonantly curing Inflammatory Bowel Disease and Irritable Bowel Syndrome. Our work on GPCR receptors common to gut inflammatory diseases and neuronal disorders through Network Pharmacology, Molecular docking and Dynamic Simulation approach has shown that modulation of these receptors with bioactive compounds present in can result in effective control of these diseases. We have found five proteins (HTR1A, HTR1B, HTR2A, HTR2B & HTR7) and five best lead compounds (Withanolide A, B, E, Q & Anahygrine) against these targets after molecular docking analysis. Our simulation studies have finally shown that amongst these five HTR1A and HTR7 proteins are the best targets with the leads Withanolide E and Withanolide A against them, respectively.Communicated by Ramaswamy H. Sarma.
人体胃肠道中的微生物对食物转化为代谢物有深远影响，而这些代谢物会影响人类健康。肠道微生物群落失调不仅在调节和调节各种代谢反应和生命过程中起着至关重要的作用，还会影响肠道和血脑屏障的通透性。这增加了阿尔茨海默病和帕金森病等与年龄相关的神经紊乱的发病几率。()被称为治疗神经退行性疾病和许多其他问题的良性植物。我们已经研究了用于治疗由肠道菌群失调引起的肠道疾病（炎症性肠病、肠易激综合征）和最常见的神经退行性疾病的组合治疗的()的生物活性成分，通过共同的潜在靶点。这种方法可以解决神经退行性疾病的治疗问题，同时还可以阻止导致这些疾病的因素进入大脑，从而协同治疗炎症性肠病和肠易激综合征。我们通过网络药理学、分子对接和动态模拟方法对肠道炎症性疾病和神经元紊乱的 GPCR 受体的研究表明，用存在于()中的生物活性化合物调节这些受体可以有效控制这些疾病。我们在分子对接分析后发现了五个针对这些靶点的蛋白质（HTR1A、HTR1B、HTR2A、HTR2B 和 HTR7）和五个最佳先导化合物（Withanolide A、B、E、Q 和 Anahygrine）。我们的模拟研究最终表明，在这五个 HTR1A 和 HTR7 蛋白中，与先导化合物 Withanolide E 和 Withanolide A 分别针对 HTR1A 和 HTR7 蛋白的是最佳靶点。由 Ramaswamy H. Sarma 传达。
