Department of Nutrition and Food Hygiene, School of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Centre for Nutritional Ecology and Centre for Sport Nutrition and Health, Zhengzhou University, Zhengzhou 450001, China.
Int J Mol Sci. 2024 Oct 25;25(21):11451. doi: 10.3390/ijms252111451.
Sarcopenia is a systemic medical disorder characterized by a gradual decline in muscular strength, function, and skeletal muscle mass. Currently, there is no medication specifically approved for the treatment of this condition. Therefore, the identification of new pharmacological targets may offer opportunities for the development of novel therapeutic strategies. The current in silico study investigated the active ingredients and the mode of action of (CRP) in addressing sarcopenia. The active ingredients of CRP and the potential targets of CRP and sarcopenia were determined using various databases. The STRING platform was utilized to construct a protein-protein interaction network, and the key intersecting targets were enriched through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Molecular docking was used to determine the binding interactions of the active ingredients with the hub targets. The binding affinities obtained from molecular docking were subsequently validated through molecular dynamics simulation analyses. Five active ingredients and 45 key intersecting targets between CRP and sarcopenia were identified. AKT1, IL6, TP53, MMP9, ESR1, NFKB1, MTOR, IGF1R, ALB, and NFE2L2 were identified as the hub targets with the highest degree node in the protein-protein interaction network. The results indicated that the targets were mainly enriched in PIK3-AKT, HIF-1, and longevity-regulating pathways. The active ingredients showed a greater interaction affinity with the hub targets, as indicated by the results of molecular docking and molecular dynamics simulations. Our findings suggest that the active ingredients of , particularly Sitosterol and Hesperetin, have the potential to improve sarcopenia by interacting with AKT1 and MTOR proteins through the PI3K-AKT signaling pathway.
肌少症是一种以肌肉力量、功能和骨骼肌质量逐渐下降为特征的全身性医学疾病。目前，尚无专门批准用于治疗这种疾病的药物。因此，寻找新的药理靶点可能为开发新的治疗策略提供机会。本计算机研究探讨了姜黄素（CRP）治疗肌少症的活性成分及其作用模式。使用各种数据库确定 CRP 和 CRP 与肌少症的活性成分和潜在靶点。使用 STRING 平台构建蛋白质-蛋白质相互作用网络，并通过京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析富集关键交集靶点。分子对接用于确定活性成分与枢纽靶点的结合相互作用。从分子对接中获得的结合亲和力随后通过分子动力学模拟分析进行验证。确定了 CRP 和肌少症之间的 5 种活性成分和 45 个关键交集靶点。在蛋白质-蛋白质相互作用网络中，AKT1、IL6、TP53、MMP9、ESR1、NFKB1、MTOR、IGF1R、ALB 和 NFE2L2 被确定为具有最高节点度的枢纽靶点。结果表明，这些靶点主要富集在 PI3K-AKT、HIF-1 和长寿调节途径中。分子对接和分子动力学模拟结果表明，活性成分与枢纽靶点的相互作用亲和力更强。我们的研究结果表明，姜黄素的活性成分，特别是甾醇和橙皮苷，通过与 AKT1 和 MTOR 蛋白相互作用，可能通过 PI3K-AKT 信号通路改善肌少症。
