关键词: PI3K/Akt pathway Penicillium sp. indole diterpenes neuroprotection

Mesh : Rats Animals PC12 Cells Proto-Oncogene Proteins c-akt / metabolism Oxidopamine / toxicity Phosphatidylinositol 3-Kinases / metabolism Penicillium / chemistry Reactive Oxygen Species / metabolism Apoptosis Diterpenes / pharmacology chemistry Indoles / pharmacology chemistry Anti-Bacterial Agents / pharmacology Neuroprotective Agents / pharmacology

来  源:   DOI:10.3390/md21110593   PDF(Pubmed)

Abstract:
In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.
摘要:
在我们对青霉菌的化学研究中。UJNMF0740源自红树林沉积物,14种吲哚二萜类似物,包括四个新的,通过多种色谱分离方法纯化,它们的结构被核磁共振分析所阐明,HR-ESIMS,和ECD数据。检查了这些分离株的抗菌和神经保护作用,只有化合物6和9表现出弱的抗菌活性,化合物5、8和10对6-羟基多巴胺(6-OHDA)诱导的PC12细胞损伤具有保护作用。此外,化合物5可以抑制6-OHDA刺激的PC12细胞的凋亡和活性氧(ROS)的产生,并触发PI3K和Akt的磷酸化。一起来看,我们的工作丰富了吲哚二萜的结构多样性,并暗示该骨架的化合物可以通过调节PI3K/Akt信号通路抑制6-OHDA诱导的PC12细胞凋亡,这为未来利用这类迷人的分子作为潜在的神经保护剂提供了证据。
公众号