Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, South Korea.
Gene. 2021 Feb 5;768:145320. doi: 10.1016/j.gene.2020.145320. Epub 2020 Nov 26.
Phellinus linteus (mushroom) grown on Rosa multiflora (PL@RM), exposed beneficial effect and safety on Type 2 diabetes mellitus (T2DM) from Korean folk remedies. However, its active chemical constituents and mechanism(s) against T2DM have not been confirmed. Hence, we deciphered the active compounds and mechanism(s) of PL@RM against T2DM through network pharmacology. GC-MS of PL@RM manifested 54 compounds and drug-likeness properties of these compounds were confirmed by Lipinski's rule. The compound (40) related genes were composed of Similarity Ensemble Approach (SEA) and SwissTargetPrediction (STP). The overlapping genes (61) between the two databases were identified. Besides, the T2DM related genes (4,736) were extracted from DisGeNet and OMIM database. In parallel, a Venn diagram was constructed between the overlapping genes (61) and T2DM related genes (4,736), and finally, 48 genes were picked. The interactive networks between compounds and overlapping genes were plotted and visualized by RStudio. In addition, KEGG Pathway enrichment analysis was evaluated by String. String analysis showed that the mechanisms of PL@RM against T2DM were related to 16 pathways, where inhibition of gluconeogenesis by inactivating metabolic pathways was noted as the hub pathway of PL@RM against T2DM. Besides, bubble chart indicated that activation of the AMPK signaling pathway might enhance the insulin receptor (IR) phosphorylation, which is regarded the key signaling pathway of PL@RM against T2DM. Furthermore, the autodock vina revealed the promising binding affinity energy of the epicholesterol (the most drug-likeness compound) on HMGCR (hub gene). Overall, this work hints at the therapeutic evidence of PL@RM on T2DM, and this data expound the main chemical compounds and mechanisms of PL@RM against T2DM.
云芝（蘑菇）寄生于悬钩子属植物（PL@RM）上，从韩国民间疗法中显示出对 2 型糖尿病（T2DM）的有益作用和安全性。然而，其针对 T2DM 的活性化学成分和机制尚未得到证实。因此，我们通过网络药理学来破译 PL@RM 对 T2DM 的活性化合物和机制。PL@RM 的 GC-MS 分析表明有 54 种化合物，这些化合物的药物相似性特性通过 Lipinski 规则得到了确认。化合物（40）相关基因由相似性集合方法（SEA）和瑞士靶标预测（STP）组成。从 DisGeNet 和 OMIM 数据库中提取了与两个数据库重叠的 61 个与 T2DM 相关的基因。此外，通过构建重叠基因（61）与 T2DM 相关基因（4736）之间的 Venn 图，最终筛选出 48 个基因。通过 RStudio 绘制化合物与重叠基因之间的相互作用网络，并进行可视化处理。此外，通过 String 对 KEGG 通路富集分析进行评估。String 分析表明，PL@RM 对 T2DM 的作用机制与 16 条通路有关，其中通过使代谢途径失活来抑制糖异生被认为是 PL@RM 对 T2DM 的关键通路。此外，气泡图表明激活 AMPK 信号通路可能增强胰岛素受体（IR）的磷酸化，这被认为是 PL@RM 对 T2DM 的关键信号通路。此外，autodock vina 揭示了最具药物相似性的化合物（epicholesterol）与 HMGCR（关键基因）结合的有前途的结合亲和力能量。总的来说，这项工作暗示了 PL@RM 对 T2DM 的治疗证据，并且这些数据阐明了 PL@RM 对 T2DM 的主要化学化合物和机制。
