Ali A, Yahya O, Al Dabbagh E
Department of Biochemistry, College of Medicine, University of Mosul, Iraq.
Georgian Med News. 2025 Feb(359):55-62.
Given its impact on glucose metabolism, the insulin receptor (IR) is considered one of the key focus areas for medical intervention in people suffering from diseases, such as diabetes mellitus. Silymarin, a natural flavonoid complex obtained from Silybum marianum (milk thistle), has been used and is known for its antioxidant and anti-inflammatory mechanisms; however, the possible effects of these compounds on the insulin receptor are yet to be fully explored. In this study, molecular docking was carried out to ascertain the binding and interaction of the active components of silymarin, such as silybin, silychristin, and silydianin, with the insulin receptor. The results from the docking simulations showed that silybin, the most important silymarin's active component, possessed relatively higher binding energies and interacted with the important key residues in the extracellular domain of the insulin receptor, suggesting possible effects on receptor activation and downstream signalling pathways that are involved in insulin's action. Moreover, the active sites on the insulin molecule possess equivalent potentials to those of silymarin, suggesting their capacity to attach to the insulin receptor. This molecular basis has led to clinical studies looking for a mechanism for which silymarin functions to alter insulin signaling, which can be targeted for the treatment of patients battling insulin resistance and diabetes. Such interactions and the possible use of such compounds in therapies can be further proved by cytometric and molecular studies depicting the usage of molecular dynamics simulations.
鉴于其对葡萄糖代谢的影响，胰岛素受体（IR）被认为是糖尿病等疾病患者医学干预的关键重点领域之一。水飞蓟素是一种从水飞蓟（奶蓟）中提取的天然类黄酮复合物，已被使用并因其抗氧化和抗炎机制而闻名；然而，这些化合物对胰岛素受体的可能影响尚未得到充分探索。在本研究中，进行了分子对接以确定水飞蓟素的活性成分如硅宾、水飞蓟素和水飞蓟宁与胰岛素受体的结合和相互作用。对接模拟结果表明，水飞蓟素最重要的活性成分硅宾具有相对较高的结合能，并与胰岛素受体细胞外结构域中的重要关键残基相互作用，提示可能对胰岛素作用所涉及的受体激活和下游信号通路产生影响。此外，胰岛素分子上的活性位点与水飞蓟素的活性位点具有同等潜力，表明它们有能力附着于胰岛素受体。这种分子基础促使了临床研究去寻找水飞蓟素改变胰岛素信号传导的机制，该机制可作为治疗胰岛素抵抗和糖尿病患者的靶点。通过描述分子动力学模拟应用的细胞计量学和分子研究可以进一步证明这种相互作用以及这些化合物在治疗中的可能用途。
